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Elafin

Tier 1 · Human trials
Also known as Peptidase inhibitor 3 · Trappin-2 · SKALP

The strongest evidence is Tier 1: a completed 87-patient randomised placebo-controlled CABG trial (src-6/7/8) and a completed Phase I single-dose escalating safety study, plus an EU-registered Phase I trial (NCT03522935). However, most disease-specific evidence (gut, HIV/HSV, cartilage, systemic sclerosis, hidradenitis suppurativa, lichen planus, reproductive tract) is observational, in vitro or animal. The pivotal CABG trial missed its primary endpoint despite strong biomarker effects. Half-life quantification, the 75-patient combined safety claim and orphan designations come from single/vendor/developer sources; general peptide context comes from a tier-3 preprint. Elafin is not approved for human therapeutic use.

Half-life
~6 h
Routes
Subcutaneous · Intravenous · Topical
Goals
Anti-inflammatory · Tissue protection / repair · Antimicrobial / antiviral · Cardiovascular / ischaemia-reperfusion protection
Cost / mg
Not recorded

How it works

Elafin (also called Trappin-2 or SKALP) is described by DrugBank as a human protein made naturally in the skin, lung and breast that protects tissue from destruction by the immune system and blocks destructive enzymes involved in inflammation. A vendor profile and reviews describe it as an endogenous serine protease inhibitor produced by epithelial cells at mucosal surfaces that blocks neutrophil enzymes (elastase and proteinase 3) and also has direct antimicrobial activity against bacteria and fungi. Because the enzyme elastase is increased in pulmonary hypertension and inflammatory tissue damage, researchers have investigated giving extra elafin to dampen this damage. In its most rigorous human test — a randomised trial in heart-bypass surgery patients — elafin dramatically raised blood elafin levels and inhibited elastase but did not reduce heart-muscle injury over 48 hours.

Overview

Overview

Elafin (also known as Peptidase inhibitor 3, Trappin-2 and SKALP; INN Tiprelestat) is an endogenous human protein under investigation as a therapeutic. DrugBank describes it as a human protein produced naturally in the skin, lung and breast that protects tissue from destruction by the immune system and blocks the activity of destructive enzymes involved in inflammatory reactions. A vendor profile characterizes it as an endogenous serine protease inhibitor peptide produced by epithelial cells at mucosal surfaces that inhibits neutrophil elastase and proteinase 3 and exhibits direct antimicrobial activity against bacteria and fungi. Although some sources describe it as 'serpin-like', this is inaccurate: elafin belongs to the WAP (whey acidic protein) four-disulfide-core family of inhibitors and blocks its target proteases by a competitive tight-binding mechanism, which is distinct from the irreversible suicide-substrate trap used by true serpins. A review (src-10) describes its structure as an N-terminal transglutaminase substrate motif and a C-terminal WAP (whey acidic protein) domain, and reports it inhibits neutrophil elastase and proteinase-3 by a competitive tight-binding mechanism.

It is not approved for human therapeutic use. Sources indicate it remains investigational; a vendor profile explicitly states it is not approved, and one EU registration notes it had no marketing authorization and was not designated an orphan drug at that time.

Development status

  • A vendor profile reports elafin is at the Phase II clinical trials stage (with 31 studies noted). A review (src-10) notes it was well tolerated in a Phase I clinical trial and that Phase II trials were underway on post-operative inflammation, focusing on reduction of post-operative morbidity after oesophagus cancer surgery, coronary artery bypass surgery and kidney transplantation.
  • A Phase I trial (NCT03522935) planned subcutaneous daily administration for 7 days in normal healthy subjects, followed over 28 days, across 5 groups of 6 subjects (30 total) at 0.03, 0.06, 0.10, 0.15 and 0.18 mg/kg, running 2019–2020. The trial states elafin inhibits elastase, an enzyme increased in pulmonary hypertension and a major factor in the development of PAH, and that elafin is being developed for treatment of PAH.
  • The developer Tiakis reports elafin (Tiprelestat), identical to the human protein, entered a Phase I trial with Duke University's Early Phase Research Unit for subcutaneous use assessing safety and tolerability of repeated single doses in healthy individuals.

Cardiac / CABG evidence

An EU-registered randomised controlled trial evaluated whether perioperative elafin infusion reduces post-ischaemic inflammatory myocardial injury following coronary artery bypass graft (CABG) surgery, enrolling 87 subjects in the UK. In that single-centre trial, 87 patients were randomised 1:1 to intravenous elafin 200 mg or saline placebo after induction of anaesthesia and prior to sternotomy. The trial authors describe elafin as a potent endogenous neutrophil elastase inhibitor that protects against myocardial inflammation and injury in preclinical models of ischaemia-reperfusion injury. Infusion was safe and produced a >3000-fold increase in plasma elafin and >50% inhibition of elastase activity in the first 24 hours. However, elafin did not reduce myocardial injury over 48 hours (ratio of geometric means AUC troponin I 0.74, 95% CI 0.47–1.15, p=0.18), had no effect on myocardial infarction (7/34 vs 5/35) nor on inflammation markers (hs-CRP p=0.16; MPO p=0.320). A post hoc analysis of the high-sensitive assay found lower troponin I at 6 hours in elafin-treated patients (median 2.4 vs 4.1 μg/L, p=0.035). The trial authors concluded there was no strong evidence that single-dose elafin reduced myocardial injury and inflammation following CABG-induced ischaemia-reperfusion injury. Note that developer (Tiakis) material describes CABG treatment as producing 'postoperative reduction of troponin I' — a more favourable framing than the trial's null primary result.

Other reported research directions

  • Pulmonary hypertension: Tiakis reports that in PAH models elafin reverses obliterative changes in arteries of lung explants from PAH patients and leads to regression of pulmonary vascular lesions in rats, and that elafin has received orphan drug designations in the USA and EU for PAH (developer-reported). A study (src-25) reports neutrophil extracellular vesicles from PAH patient plasma induced pulmonary hypertension in mice, an effect mitigated by elafin.
  • Gut/inflammatory bowel: Reviews describe trappin-2/elafin contributing to the mucosal shield against luminal microbes and report accumulating evidence of protective effects in gut disorders and gluten sensitization, considering therapeutic potential of mucosal delivery.
  • Antimicrobial/antiviral: In vitro studies report recombinant trappin-2/elafin inhibits HIV-1 (elafin ~130× more potent than trappin-2) and HSV-2 (elafin ~7× more potent), inhibits HIV-1 attachment and transcytosis, and that a transgenic mouse study found reduced HSV-2 viral load in the CNS. A mouse study (src-39) found elafin active against Pseudomonas aeruginosa via adenovirus-mediated gene transfer.
  • Skin: A study describes elafin as absent in normal skin but highly expressed in inflamed skin keratinocytes, with overexpression reported in cellulitis, psoriasis, Behçet's syndrome and graft versus host disease. Serum elafin was significantly higher in lichen planus patients than controls (32.56 vs 5.60 ng/mL, p<0.001). SKALP/elafin mRNA was significantly elevated in lesional hidradenitis suppurativa skin.
  • Other: Observational studies report elevated trappin-2 in osteoarthritis cartilage and correlations with renal dysfunction and pulmonary pressure in systemic sclerosis; a reproductive-tract study found elafin diminished with bacterial vaginosis.

Most of this disease-specific evidence is in vitro, animal or observational; human efficacy in these indications has not been established. A tier-3 preprint review provides general context on peptide drugs, projecting global sales of approved peptide drugs to reach ~$75 billion by 2028 and warning of a gray market of unapproved peptides sold direct-to-consumer.

What the research shows

213 findings extracted from the 30 sources cited below, strongest evidence first within each group. Every one links to the source it came from.

What human studies found

Based on 16 human trial findings, 26 human study findings, 5 animal findings, 1 in vitro finding and 4 expert opinion findings.

  • human trialA placebo-controlled randomized trial evaluated the effect of elafin on cytokine profiles after major surgery in a Phase II trial1

  • human trialStudy was single center and performed with approval of national research ethics committee and MHRA2

  • human trialElafin (INN: Tiprelestat) entered Phase I clinical trial for subcutaneous use assessing safety and tolerability of repeated single doses in healthy individuals5

  • human trialElafin did not reduce myocardial injury over 48 h (ratio of geometric means (elafin/placebo) of AUC troponin I 0.74 (95% CI 0.47 to 1.15, p=0.18))7

  • human trialPost hoc analysis of the high-sensitive assay revealed lower troponin I concentrations at 6 h in elafin-treated patients (median 2.4 vs 4.1 μg/L, p=0.035)7

  • human trialElafin had no effect on myocardial infarction (elafin, 7/34 vs placebo, 5/35 patients)7

  • human trialElafin had no effect on markers of inflammation: mean differences for AUC hs-CRP of 499 mg/L/48 h (95% CI -207 to 1205, p=0.16), and AUC MPO of 238 ng/mL/48 h (95% CI -235 to 711, p=0.320)7

  • human trialElafin did not reduce myocardial injury over 48 h (ratio of geometric means (elafin/placebo) of AUC troponin I 0.74 (95% CI 0.47 to 1.15, p=0.18))8

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  • human trialPost hoc analysis of the high-sensitive assay revealed lower troponin I concentrations at 6 h in elafin-treated patients (median 2.4 vs 4.1 μg/L, p=0.035)8

  • human trialElafin had no effect on myocardial infarction (elafin, 7/34 vs placebo, 5/35 patients)8

  • human trialElafin had no effect on markers of inflammation: mean differences for AUC hs-CRP of 499 mg/L/48 h (95% CI -207 to 1205, p=0.16), and AUC MPO of 238 ng/mL/48 h (95% CI -235 to 711, p=0.320)8

  • human trialElafin did not reduce myocardial injury over 48 h (ratio of geometric means (elafin/placebo) of AUC troponin I 0.74 (95% CI 0.47 to 1.15, p=0.18))9

  • human trialPost hoc analysis of the high-sensitive assay revealed lower troponin I concentrations at 6 h in elafin-treated patients (median 2.4 vs 4.1 μg/L, p=0.035)9

  • human trialElafin had no effect on myocardial infarction (elafin, 7/34 vs placebo, 5/35 patients)9

  • human trialElafin had no effect on markers of inflammation: mean differences for AUC hs-CRP of 499 mg/L/48 h (95% CI -207 to 1205, p=0.16), and AUC MPO of 238 ng/mL/48 h (95% CI -235 to 711, p=0.320)9

  • human trialThere was no strong evidence that neutrophil elastase inhibition with a single-dose elafin treatment reduced myocardial injury and inflammation following CABG-induced ischaemia-reperfusion injury9

  • human studyTreatment of patients undergoing esophageal cancer surgery resulted in significantly shorter intensive care unit stay and positive postoperative effect on liver and kidney markers5

  • human studyTreatment of patients undergoing coronary artery bypass surgery resulted in postoperative reduction of the heart damage marker troponin I5

  • human studyOverexpression of Elafin has been reported in various infective, inflammatory skin disorders, such as cellulitis, psoriasis, Behçet's syndrome, and graft versus host disease6

  • human studySerum Elafin level was significantly higher in LP patients as compared to healthy controls6

  • human studySLPI and elafin are often inactivated in inflammatory secretions in patients with chronic pathologies in the lung and elsewhere10

  • human studyAntiprotease supplementation with SLPI/elafin in clinical protocols has demonstrated proof of principle10

  • human studyElafin was found in all 112 samples of cervicovaginal secretions11

  • human studyElafin levels were diminished in women with bacterial vaginosis11

  • human studyElafin is a component of cervicovaginal secretions in pregnancy11

  • human studyTrappin-2 was detectable in OA articular cartilage extracts, cultured chondrocytes, conditioned media, and SF by Western blotting12

  • human studyOA cartilage protein extracts contained significantly higher quantities of trappin-2 than normal cartilage protein extracts12

  • human studyImmunohistochemical studies of OA cartilage revealed trappin-2 protein in chondrocytes12

  • human studyExpression of trappin-2/elafin is differentially regulated in diseases associated with gut inflammation17

  • human studyTrappin-2/elafin has protective effects in gut intestinal disorders associated with acute or chronic inflammation17

  • human studyTrappin-2/elafin has protective effects in gluten sensitization disorders17

  • human studyNeutrophils from patients with pulmonary arterial hypertension produce and release increased neutrophil elastase, associated with enhanced extracellular traps18

  • human studySKALP/elafin mRNA expression is significantly elevated in lesional compared with nonlesional skin of hidradenitis suppurativa patients19

  • human studySerum trappin-2 levels inversely correlated with estimated glomerular filtration rate in SSc patients with renal dysfunction20

  • human studySerum trappin-2 levels were significantly increased in SSc patients with digital ulcers or elevated RVSP compared to those without20

  • human studySerum trappin-2 levels positively correlated with RVSP values in SSc patients20

  • human studyPrevalence of digital ulcers or elevated right ventricular systolic pressure (RVSP) was significantly higher in SSc patients with elevated serum trappin-2 levels than in those with normal levels20

  • human studyTrappin-2 expression was enhanced in small vessels of SSc lesional skin20

  • human studyEndothelial trappin-2 up-regulation partially due to Fli1 deficiency can be associated with the development of SSc vasculopathy20

  • human studyTr/E are among principal anti-HIV-1 molecules in cervicovaginal lavage (CVL) fluid21

  • human studyAverage levels of secreted Trappin-2/Elafin were higher in cervico-vaginal lavages from HIV-negative women compared to HIV-positive women, although values did not reach statistical significance24

  • human studyWomen at the secretory phase of the menstrual cycle produced more Trappin-2/Elafin in cervico-vaginal lavages relative to women at the proliferative phase24

  • animalStudies on several animal models show that antiprotease augmentation with human elafin is an effective strategy in the treatment of inflammatory vascular, systemic and pulmonary diseases4

  • animalStudies on several animal models show that antiprotease augmentation with human elafin is an effective strategy in treatment of inflammation triggered by reperfusion injury4

  • animalTreatment with Elafin leads to regression of pulmonary vascular lesions in rats5

  • animalTrappin-2/Elafin linked to susceptibility or protection against inflammatory disease and infections22

  • animalElafin is active against Pseudomonas aeruginosa infection in mice in vivo using an adenovirus-mediated gene transfer overexpression strategy27

  • in vitroRecombinant Trappin-2/Elafin was able to inhibit both T-cell-tropic X4/IIIB and macrophage-tropic R5/BaL HIV-1 in a dose-dependent manner24

  • expert opinionAccumulating evidence has demonstrated the protective effects of trappin-2/elafin in gut intestinal disorders associated with acute or chronic inflammation, or with gluten sensitization disorders13

  • expert opinionRecombinant elafin is in Phase 2 trials28

  • expert opinionElafin is currently at the Phase II clinical trials stage28

  • expert opinionApproved peptide drugs undergo a rigorous path of development and approval, with extensive clinical trials often consisting of thousands of subjects to establish efficacy and safety29

How it works

Based on 2 human trial findings, 22 human study findings, 4 animal findings, 59 in vitro findings, 21 expert opinion findings and 5 theoretical findings.

  • human trialElafin resulted in >50% inhibition of elastase activity in the first 24 h7

  • human trialElafin resulted in >50% inhibition of elastase activity in the first 24 h8

  • human studyElafin could be part of the inflammatory autoimmune process in LP6

  • human studyElafin and secretory leukocyte protease inhibitor (SLPI) are pleiotropic molecules chiefly synthesized at the mucosal surface10

  • human studyElafin and SLPI have a fundamental role in the surveillance against microbial infections10

  • human studyElafin functions as an anti-protease in the inflammatory milieu10

  • human studyElafin has antimicrobial function10

  • human studyElafin modulates innate and adaptive immunity10

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  • human studyElafin regulates tissue repair10

  • human studyInactivation of SLPI and elafin occurs through the action of host or microbial products10

  • human studyElafin is expressed in the cervical glandular epithelium11

  • human studyElafin may be an important component of innate immunity in the lower genital tract11

  • human studyTrappin-2 is present in many tissues and is upregulated at sites of injury12

  • human studyIn osteoarthritis (OA), serine proteases contribute to articular cartilage destruction12

  • human studyTGase activity is increased in OA cartilage12

  • human studyRT-PCR confirmed the presence of trappin-2 mRNA in OA chondrocytes12

  • human studyFibromodulin was bound to trappin-2 in cartilage12

  • human studyElevated levels of TGase activity in OA cartilage may increase levels of this serine protease inhibitor in response to injury12

  • human studyThe expression of trappin-2/elafin has been shown to be differentially regulated in diseases associated with gut inflammation13

  • human studyNOD2 mRNA expression correlates with SKALP/elafin expression (r=0.65; P<0.01) in hidradenitis suppurativa skin19

  • human studyNOD2 signalling activation in hidradenitis suppurativa might contribute to pathogenesis via induction of antimicrobial peptides including elafin19

  • human studyElafin (E) and its precursor, trappin-2 (Tr) have been associated with mucosal resistance to HIV-1 infection21

  • human studyEx vivo incubation of trappin-2 with sputum from cystic fibrosis patients produced a proteolytic immunoreactive fragment with the same mass as native elafin26

  • human studyCleavage by sputum did not occur when preincubating sputum with polyclonal antibodies directed against tryptase26

  • animalElafin is a potent endogenous neutrophil elastase inhibitor that protects against myocardial inflammation and injury in preclinical models of ischaemic-reperfusion injury8

  • animalElafin is a potent endogenous neutrophil elastase inhibitor that protects against myocardial inflammation and injury in preclinical models of ischaemic-reperfusion injury9

  • animalNeutrophil EVs from patient plasma contain increased neutrophil elastase and human endogenous retrovirus K envelope and induce pulmonary hypertension in mice, mitigated by elafin, an elastase inhibitor18

  • animalIn vivo studies of intravaginal HSV-2 infection in Tr-transgenic mice (Etg) showed that despite similar virus replication in the genital tract, Etg mice had reduced viral load and TNF-α in the central nervous system compared to controls21

  • in vitroIn models of PAH, Elafin reverses obliterative changes in arteries of lung explants from PAH patients5

  • in vitroInterleukin 1beta (IL-1beta) stimulated elafin expression in cells derived from the endocervix, but not in those derived from the vaginal epithelium11

  • in vitroElafin inhibits cathepsin S and protease-activated receptor 2 activities14

  • in vitroElafin reduces collagen synthesis in intestinal fibroblasts14

  • in vitroElafin and its precursor trappin-2 contribute to the physiological mucosal shield against luminal microbes17

  • in vitroTrappin-2/elafin acts as protease inhibitors17

  • in vitroTrappin-2/elafin acts as transglutaminase substrates17

  • in vitroTrappin-2/elafin acts as antimicrobial peptides17

  • in vitroTrappin-2/elafin acts as a regulator of pro-inflammatory transcription factors17

  • in vitroIn unstimulated normal keratinocytes, SKALP/elafin expression significantly increases from 6 to 48 hours19

  • in vitroIn Pam2-stimulated normal keratinocytes, SKALP/elafin expression significantly increases from 6 to 48 hours19

  • in vitroIn MDP-stimulated normal keratinocytes, SKALP/elafin expression significantly increases from 6 to 48 hours19

  • in vitroIn unstimulated, Pam2-stimulated and MDP-stimulated hidradenitis suppurativa keratinocytes, SKALP/elafin expression significantly declines from 6 to 48 hours19

  • in vitroSKALP/elafin mRNA expression at 6 hours is significantly increased in hidradenitis suppurativa compared with normal keratinocytes under unstimulated and Pam2-stimulated conditions19

  • in vitroTrappin-2 expression was elevated by gene silencing of FLI1 at mRNA and protein levels in cultured endothelial cells20

  • in vitroFli1 occupied the PI3 promoter20

  • in vitroE is ∼130 times more potent than Tr against HIV-121

  • in vitroTr/E inhibited HIV-1 attachment and transcytosis across human genital epithelial cells (ECs)21

  • in vitroPretreatment of endometrial (HEC-1A) and endocervical (End1/E6E7) ECs with human Tr-expressing adenovirus (Ad/Tr) or recombinant Tr/E proteins before or after HSV-2 infection resulted in significantly reduced virus titers compared to controls21

  • in vitroE was ∼7 times more potent against HSV-2 infection than Tr21

  • in vitroKnockdown of endogenous Tr/E by small interfering RNA (siRNA) significantly increased HSV-2 replication in genital ECs21

  • in vitroRecombinant Tr and E reduced viral attachment to genital ECs by acting indirectly on cells21

  • in vitroLower viral replication was associated with reduced secretion of proinflammatory interleukin 8 (IL-8) and tumor necrosis factor alpha (TNF-α) and decreased NF-κB nuclear translocation21

  • in vitroProtected Ad/Tr-treated ECs demonstrated enhanced interferon regulatory factor 3 (IRF3) nuclear translocation and increased antiviral IFN-β in response to HSV-221

  • in vitroTrappin-2/Elafin is a potent serine protease inhibitor which prevents excessive damage under inflammatory status22

  • in vitroTrappin-2/Elafin is locally expressed by epithelial cells and immune cells such as macrophages and γδ T cells22

  • in vitroTrappin-2/Elafin modulates the NFκB pathway22

  • in vitroTrappin-2/Elafin modulates cytokine secretion22

  • in vitroTrappin-2/Elafin modulates cell recruitment22

  • in vitroTrappin-2/Elafin possesses anti-microbial properties against viruses, fungi and bacteria22

  • in vitroHuman lungs contain secretory leukocyte protease inhibitor (SLPI), elafin and its biologically active precursor trappin-2 (pre-elafin)23

  • in vitroElafin and trappin-2 are low-molecular weight inhibitors involved in controlling proteolytic activities of neutrophil serine proteases including elastase, proteinase 3 and cathepsin G23

  • in vitroTrappin-2 and to a lesser extent, elafin can be linked covalently to various extracellular matrix proteins by tissue transglutaminases and remain potent protease inhibitors23

  • in vitroSLPI is composed of two distinct domains, each of which is about 40% identical to elafin23

  • in vitroTrappin-2 and elafin have consensus transglutaminase sequences, unlike SLPI23

  • in vitroType 2 tissue transglutaminase and plasma transglutaminase activated factor XIII can covalently bind SLPI to fibronectin or elastin23

  • in vitroCross-linked SLPI retains the ability to inhibit target proteases elastase and cathepsin G23

  • in vitroThe transglutamination substrate status of the cementoin domain of trappin-2 can be transferred from one protein to another, suggesting it may provide transglutaminase-dependent attachment properties for engineered proteins23

  • in vitroTrappin-2/Elafin is a serine protease inhibitor that plays a major role as an anti-inflammatory mediator at mucosal surfaces24

  • in vitroTrappin-2/Elafin has antibacterial activity against Gram-positive and Gram-negative bacterial and fungal pathogens24

  • in vitroPrimary uterine, Fallopian tube, cervical and ectocervical epithelial cells produce Trappin-2/Elafin constitutively24

  • in vitroProduction of Trappin-2/Elafin is enhanced following stimulation with Poly(I:C), especially by uterine cells24

  • in vitroThe mechanism of HIV-1 inhibition by Trappin-2/Elafin is likely a direct interaction between HIV-1 and Trappin-2/Elafin24

  • in vitroElafin and its precursor trappin prevent neutrophil proteinase-mediated lung tissue destruction25

  • in vitroMyeloperoxidase/H2O2 and N-chlorosuccinimide oxidation significantly lowers the affinities of elafin and trappin for neutrophil elastase (NE) and proteinase 3 (Pr3)25

  • in vitroOxidation of elafin and trappin causes an increase in the rate of inhibitory complex dissociation25

  • in vitroOxidized elafin and trappin are unable to efficiently inhibit the elastolytic activity of NE and Pr3 despite maintaining reasonable affinities25

  • in vitroAt physiological concentration, fully oxidized elafin does not inhibit more than 30% of an equimolar concentration of NE or Pr325

  • in vitroSerine and cysteine proteases preferentially cleaved trappin-2 within its non-inhibitory N-terminal moiety26

  • in vitroCathepsin L, cathepsin K, plasmin, trypsin and tryptase were able to release elafin by cleaving the Lys 38-Ala 39 peptide bond in trappin-226

  • in vitroPurified tryptase appeared to be efficient at releasing elafin26

  • in vitroIncubation of trappin-2 with purified mast cells challenged with anti-immunoglobulin E or calcium ionophore A23187 resulted in rapid generation of elafin26

  • in vitroProteolytic release of elafin from trappin-2 was inhibited in the presence of a tryptase inhibitor, suggesting mast cell tryptase was involved26

  • in vitroTryptase could likely be involved in the maturation of trappin-2 into elafin under physiological conditions26

  • in vitroLow-molecular-mass neutrophil elastase inhibitors have been shown to be important in the control of lung inflammation27

  • in vitroSecretory leucocyte proteinase inhibitor (SLPI) and elastase-specific inhibitor/SKALP (skin-derived antileucoproteinase)/elafin have been shown to have 'defensin'-like antimicrobial activities27

  • in vitroThese inhibitors have antimicrobial properties in vitro against bacteria, fungi and, potentially, HIV27

  • in vitroLipopolysaccharide is able to up-regulate SLPI production in macrophages in vitro27

  • in vitroRecombinant SLPI added to human monocytes or transfection of macrophages with SLPI can down-regulate pro-inflammatory mediators such as tumour necrosis factor27

  • expert opinionElafin inhibits elastase, an enzyme that is increased in pulmonary hypertension and is a major factor in the development of PAH3

  • expert opinionElafin is an endogenous human protein composed of an N-terminal transglutaminase substrate motif and a C-terminal WAP (whey acidic protein)-domain with antiproteolytic properties4

  • expert opinionElafin is expressed predominantly in epithelial tissue4

  • expert opinionElafin potently inhibits the neutrophil-derived serine proteases elastase and proteinase-3 by a competitive tight-binding mechanism4

  • expert opinionElafin inhibits EVE (endogenous vascular elastase)4

  • expert opinionElafin is identical to the human protein elafin with high specificity for tissue destroying and inflammation promoting proteases5

  • expert opinionElafin is an epithelial host-defense protein that is absent in normal skin but highly expressed in inflamed skin keratinocytes6

  • expert opinionElafin and its precursor trappin-2 are known for their contribution to the physiological mucosal shield against luminal microbes13

  • expert opinionThe protective effects of trappin-2/elafin in the gut are mediated through pleiotropic modes of action: acting as protease inhibitors, transglutaminase substrates, antimicrobial peptides or as a regulator of pro-inflammatory transcription factors13

  • expert opinionElafin is a human protein that is produced naturally in the skin, lung and breast15

  • expert opinionElafin protects tissue from destruction by the immune system15

  • expert opinionElafin blocks the activity of destructive enzymes that are involved in inflammatory reactions15

  • expert opinionPeptides interact with specific receptors to elicit highly selective biological responses, analogous to those induced by larger biologics, yet with enhanced pharmacokinetic flexibility16

  • expert opinionPeptides often demonstrate higher specific activity per unit mass, i.e., ~15-60 times that of antibodies, due to their lower molecular weight and more efficient receptor engagement16

  • expert opinionElafin is an elastase inhibitor18

  • expert opinionElafin is an endogenous serine protease inhibitor (serpin-like) peptide produced by epithelial cells at mucosal surfaces28

  • expert opinionElafin inhibits neutrophil elastase and proteinase 3, protecting tissues from excessive inflammatory damage28

  • expert opinionElafin exhibits direct antimicrobial activity against bacteria and fungi28

  • expert opinionPeptides are molecules composed of up to 40 to 50 amino acids29

  • expert opinionPeptides occupy a distinct biochemical and regulatory niche between small-molecule drugs (generally <500 Daltons) and large biological proteins (>5000 Daltons)29

  • expert opinionPeptides function as potent signaling molecules for numerous physiological processes29

  • theoreticalElafin is a biological/biotechnological origin active substance1

  • theoreticalElafin is a potent endogenous neutrophil elastase inhibitor that protects against myocardial inflammation and injury in preclinical models of ischaemic-reperfusion injury7

  • theoreticalThe contribution of trappin-2/elafin to mucosal protection is particularly relevant in the gut due to constant microbial exposure17

  • theoreticalTrappin-2/pre-elafin is an endogenous inhibitor of human neutrophil elastase involved in inflammation, innate immunity and vascular remodelling20

  • theoreticalOxidized elafin has reasonable affinity for NE and Pr3 theoretically sufficient to form tight binding complexes in lung secretions25

Dosing

Based on 5 human trial findings, 1 expert opinion finding and 2 theoretical findings.

  • human trialElafin was administered as an infusion in a randomised-controlled trial2

  • human trialElafin will be administered subcutaneously daily for 7 days in normal healthy subjects followed over a 28 day time period3

  • human trial87 patients undergoing CABG surgery were randomised 1:1 to intravenous elafin 200 mg or saline placebo administered after induction of anaesthesia and prior to sternotomy7

  • human trialElafin 200 mg was administered intravenously after induction of anaesthesia and prior to sternotomy8

  • human trial87 patients undergoing CABG surgery were randomised 1:1 to intravenous elafin 200 mg or saline placebo administered after induction of anaesthesia and prior to sternotomy9

  • expert opinionIn research settings, Elafin is typically administered via topical and intravenous routes28

  • theoreticalElafin is formulated as a solution for infusion1

  • theoreticalElafin is administered intravenously1

How the body handles it

Based on 5 human trial findings, 1 expert opinion finding and 1 theoretical finding.

  • human trialPharmacokinetic/pharmacodynamic (PK/PD) and immunogenicity parameters in blood sample will be assessed including AUC0-last3

  • human trialElafin infusion was safe and resulted in >3000-fold increase in plasma elafin concentrations7

  • human trialElafin resulted in >3000-fold increase in plasma elafin concentrations8

  • human trialElafin resulted in >3000-fold increase in plasma elafin concentrations9

  • human trialElafin achieved >50% inhibition of elastase activity in the first 24 h9

  • expert opinionThe reported half-life of Elafin is ~4–8 hours28

  • theoreticalElafin has a short half-life14

Safety and side effects

Based on 6 human trial findings, 6 expert opinion findings and 1 theoretical finding.

  • human trialSafety and tolerability will be determined on the basis of adverse events reported and the severity of adverse events3

  • human trialIn a Phase I clinical trial, elafin was well tolerated4

  • human trialNo safety concerns after treatment of 75 patients in three randomized, double-blind, placebo-controlled clinical trials5

  • human trialElafin infusion was safe8

  • human trialElafin infusion was safe9

  • human trialThe excellent tolerability of Elafin in human subjects was demonstrated in a Phase I clinical single dose escalating study15

  • expert opinionPeptides generally demonstrate favorable safety profiles with minimal adverse events, effective target engagement, and clinically meaningful efficacy16

  • expert opinionElafin is not approved for human therapeutic use28

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  • expert opinionA parallel and pervasive gray market has emerged, driven by direct-to-consumer sales of unapproved peptides29

  • expert opinionUnapproved peptides are frequently carrying disclaimers like 'research chemical' or 'not for human consumption' to circumvent regulatory oversight29

  • expert opinionUnapproved peptides are aggressively marketed to the general public through social media and online forums29

  • expert opinionPeptides produced on the gray market are not subject to Good Manufacturing Practice (cGMP) guidelines or regulatory oversight29

  • theoreticalElafin did not have marketing authorization at the time of this trial1

What people use it for

Based on 2 human trial findings, 11 expert opinion findings and 3 theoretical findings.

  • human trialPerioperative elafin administration reduces post-ischaemic inflammatory myocardial injury following coronary artery bypass graft surgery2

  • human trialElafin is being developed for treatment of PAH3

  • expert opinionPhase II trials are underway to investigate the therapeutic effects of elafin on post-operative inflammation and the clinical consequences of major surgery4

  • expert opinionPhase II trials focus on reduction of post-operative morbidity after oesophagus cancer surgery, coronary artery bypass surgery and kidney transplantation4

  • expert opinionElafin has received orphan drug designations in the USA and EU for PAH treatment5

  • expert opinionTrappin-2/elafin contribution seems to be particularly relevant in the gut, where the exposure of host tissues to heavy loads of microbes is constant and contributes to mucosa-associated pathologies13

  • expert opinionTherapeutic potential of trappin-2/elafin delivery at the intestinal mucosa surface is being considered13

  • expert opinionTrappin-2/elafin mucosal delivery should be considered to ensure intestinal tissue repair13

Show the remaining 8

  • expert opinionElafin is a highly promising active compound for the treatment of inflammatory lung diseases15

  • expert opinionElafin is a highly promising active compound for the treatment of severe reperfusion injuries occurring after heart attacks, serious injuries and organ transplantation15

  • expert opinionElafin is investigated for use/treatment in inflammatory disorders15

  • expert opinionTrappin-2/Elafin might be an important endogenous microbicide of the female reproductive tract that is protective against HIV-124

  • expert opinionResearch focuses on inflammatory bowel disease, cystic fibrosis, ARDS, and vaginal microbiome modulation28

  • theoreticalTherapeutic potential of trappin-2/elafin delivery at the intestinal mucosa surface is being considered17

  • theoreticalTrappin-2/elafin mucosal delivery may ensure intestinal tissue repair17

  • theoreticalIn vivo oxidation of elafin strongly impairs its activity in inflammatory lung diseases25

Other findings

Based on 2 expert opinion findings and 2 theoretical findings.

  • expert opinionChallenges remain in improving peptide stability and delivery, with innovations in cyclization, conjugation, and nano-formulation showing promise16

  • expert opinionGlobal sales of approved peptide drugs will likely reach $75 billion USD by 202829

  • theoreticalElafin was not designated as an orphan drug1

  • theoreticalElafin is not mentioned in this source30

Points of contention

Where the evidence is unsettled, thin, or says less than the popular claim — worth knowing before you draw conclusions.

Contested

Elafin's key CABG trial missed its primary endpoint despite strong biomarker effects

The 87-patient randomised CABG trial showed elafin produced a >3000-fold rise in plasma elafin and >50% elastase inhibition, yet did not reduce myocardial injury over 48 h (AUC troponin I ratio 0.74, p=0.18) and had no effect on infarction or inflammation markers; only a post hoc analysis showed lower 6-hour troponin I (p=0.035). Company (Tiakis) material meanwhile describes CABG treatment as producing 'postoperative reduction of troponin I,' a more favourable framing than the trial's own null primary result.

Single source

The ~4–8 hour half-life figure comes only from a tier-3 vendor page

The specific half-life estimate of ~4–8 hours is reported only by a tier-3 vendor/research web profile; other sources describe elafin merely as having 'a short half-life' without quantification.

Single source

The 75-patient safety claim across three trials comes only from the developer

The statement of no safety concerns after treating 75 patients in three randomized, double-blind, placebo-controlled trials, and the PAH orphan drug designations, are reported by the company Tiakis Biosciences rather than an independent source.

Other

Elafin is not approved for human therapeutic use

Sources indicate elafin remains investigational (Phase I/II), had no marketing authorization at trial time and is not designated as an orphan drug in one EU registration, and a vendor profile explicitly states it is not approved for human therapeutic use.

Preprint

General peptide market and safety context comes from a preprint

Broad claims about peptide definitions, the projected $75 billion market by 2028, and gray-market safety concerns come from a tier-3 preprint review not specific to elafin.

Using it with other compounds

Check a stack
  • TB-500Complementary

    May be complementary

    TB-500 promotes cell migration, angiogenesis and matrix remodeling for wound healing, while elafin protects healing tissue by inhibiting neutrophil proteases and suppressing NF-κB inflammation. Distinct mechanisms both favoring tissue repair.

    Tier 3Largely anecdotal — commonly discussed

    What the research doesn't fully establish

    Both peptides' mechanisms clearly support the proposed complementary relationship with the three shared dimensions. Elafin inhibits neutrophil elastase, proteinase 3, and cathepsin S while modulating NF-κB and providing tissue protection at mucosal surfaces. TB-500 promotes angiogenesis, cell migration, matrix remodeling, and suppresses NF-κB/TNF-α/IL-1β/IL-6. Both are tagged with tissue_repair, anti_inflammatory, and NF_kB_modulation. The explanation accurately reflects their distinct but synergistic mechanisms: elafin acts as a protease inhibitor preventing tissue destruction during inflammation, while TB-500 actively promotes healing through cytoskeletal dynamics and angiogenesis. These represent complementary approaches to tissue repair—one protective/anti-inflammatory, one regenerative—both converging on NF-κB modulation and inflammation resolution.

    Shares tissue repair · anti inflammatory · NF kB modulation

  • KPVComplementary

    May be complementary

    Both dampen inflammation at mucosal surfaces largely by restraining NF-κB signaling, but by different means: KPV (an α-MSH fragment) suppresses inflammatory cytokines and stabilizes IκBα, while elafin blocks tissue-destroying proteases. In a gut/mucosal setting they address inflammation and barrier protection from complementary angles.

    Tier 3Largely anecdotal — commonly discussed

    What the research doesn't fully establish

    The mechanisms clearly establish complementary roles in mucosal inflammation control. Both peptides share three documented dimensions: (1) innate_immune function—elafin via protease inhibition and antimicrobial activity, KPV via immunomodulation and cytokine suppression; (2) anti_inflammatory effects—elafin through NF-κB modulation and tissue protection, KPV through TNF-α/IL-1β/IL-6 suppression; (3) NF-κB_modulation—elafin via NF-κB pathway modulation (src-17, src-23), KPV via IκBα stabilization and IKK complex inhibition. The explanation accurately characterizes their distinct mechanisms: KPV acts through cytokine suppression and IκBα stabilization, while elafin acts through protease inhibition and tissue protection. Both target mucosal barrier integrity and inflammation resolution in overlapping contexts (gut/mucosal surfaces), making them genuinely complementary rather than redundant. The proposed relationship type and shared dimensions are directly supported by the provided mechanism material.

    Shares innate immune · anti inflammatory · NF kB modulation

  • LL-37Complementary

    May be complementary

    Both are human host-defense molecules but hit different targets: LL-37 is a cathelicidin that directly punctures microbial membranes, while elafin blocks the destructive enzymes (elastase, proteinase 3) that neutrophils release. Together they cover both direct killing and protection of the tissue from friendly-fire enzyme damage, converging on mucosal defense and repair.

    Tier 3Largely anecdotal — commonly discussed

    What the research doesn't fully establish

    The proposed relationship is well-justified by the mechanism material. Both peptides share the four claimed dimensions: (1) innate_immune—both are explicitly tagged and described as host-defense molecules with immune modulation roles; (2) antimicrobial—both have broad-spectrum antimicrobial activity documented; (3) anti_inflammatory—both are tagged and show anti-inflammatory effects; (4) tissue_repair—both are tagged with tissue repair/mucosal protection roles. The 'complementary' relationship type is strongly supported: the mechanisms show distinct but synergistic modes of action—LL-37 targets membrane receptors (FPR2, TLRs) and directly kills microbes, while elafin inhibits neutrophil serine proteases (elastase, proteinase 3) to prevent tissue damage. The explanation accurately reflects that they converge on mucosal defense through different mechanisms: direct antimicrobial activity versus protection from collateral enzyme damage. This is a textbook complementary relationship where both peptides address the same biological problem (mucosal defense) via non-overlapping mechanisms.

    Shares innate immune · antimicrobial · anti inflammatory · tissue repair

  • TeduglutideComplementary

    May be complementary

    Teduglutide drives intestinal epithelial growth and barrier repair through the GLP-2 receptor, while elafin protects that same mucosa by neutralizing destructive proteases and calming inflammation. Different mechanisms both supporting gut mucosal integrity and repair.

    Tier 3Largely anecdotal — commonly discussed

    What the research doesn't fully establish

    Both peptides' mechanisms clearly support mucosal_repair and tissue_repair functions through distinct but complementary pathways. Elafin inhibits neutrophil serine proteases (elastase, proteinase 3) and modulates NF-κB/inflammatory signaling to protect mucosal tissue from enzymatic destruction. Teduglutide activates GLP-2 receptor signaling to promote intestinal epithelial growth, proliferation, and barrier function. The mechanisms describe non-overlapping approaches to the same tissue outcome: one protective/anti-degradative, one growth/regenerative. Both are explicitly tagged with mucosal_repair and tissue_repair in their approved tags, and the explanation accurately reflects how their distinct molecular mechanisms would work synergistically on intestinal mucosa.

    Shares mucosal repair · tissue repair

  • PidotimodComplementary

    No documented conflict

    Pidotimod stimulates dendritic cell maturation and T-cell responses against recurrent infections, while elafin provides direct antiprotease and antimicrobial protection at epithelial surfaces. Complementary adaptive-plus-innate host defense.

    Tier 4Theoretical — not established

    What the research doesn't fully establish

    Both peptides' mechanisms clearly support the claimed shared dimensions and complementary relationship. Elafin targets innate immune proteases (neutrophil elastase, proteinase 3, cathepsin G/S) and provides direct antimicrobial activity with tissue protection at mucosal surfaces. Pidotimod stimulates innate immunity through TLR signaling and dendritic cell maturation while enhancing adaptive responses (T-cell proliferation, Th1 differentiation). Both are tagged with innate_immune, anti_inflammatory, and antimicrobial. The explanation accurately describes their distinct but complementary mechanisms: elafin acts as a direct protease inhibitor and antimicrobial agent at epithelial barriers, while pidotimod enhances immune cell activation and adaptive responses. These mechanisms work synergistically rather than redundantly, justifying the 'complementary' relationship type.

    Shares innate immune · anti inflammatory · antimicrobial

  • ThymulinComplementary

    No documented conflict

    Thymulin normalizes T-cell balance and tamps down excess pro-inflammatory cytokines via NF-κB inhibition, while elafin controls neutrophil protease-driven tissue damage. They modulate adaptive and innate immunity from different angles toward a calmer, better-regulated immune response.

    Tier 4Theoretical — not established

    What the research doesn't fully establish

    Both peptides' mechanisms clearly support the proposed complementary relationship across all three claimed shared dimensions. (1) Innate_immune: Elafin directly inhibits neutrophil serine proteases (elastase, proteinase 3) and shows antimicrobial activity; Thymulin enhances NK cell cytotoxicity and modulates innate responses. (2) Anti_inflammatory: Elafin is explicitly tagged anti_inflammatory with NF-κB pathway modulation; Thymulin suppresses excessive proinflammatory cytokine production (TNF-alpha, IL-1beta, IL-6) and is tagged anti_inflammatory. (3) NF_kB_modulation: Both mechanisms explicitly reference NF-κB pathway involvement (Elafin: src-17, src-23; Thymulin: NF-κB inhibition reported). The explanation accurately characterizes their distinct but complementary mechanisms—elafin controlling neutrophil protease-driven innate damage while thymulin normalizes T-cell balance and cytokine production—both converging on immune regulation through NF-κB modulation. The mechanisms justify calling them complementary rather than redundant.

    Shares innate immune · anti inflammatory · NF kB modulation

  • ImunofanComplementary

    No documented conflict

    Imunofan is a thymopoietin-based immunomodulator that boosts phagocytic/antimicrobial defenses and supports tissue repair, complementing elafin's antiprotease and antimicrobial actions. Different mechanisms supporting immune balance and mucosal repair.

    Tier 4Theoretical — not established

    What the research doesn't fully establish

    Both peptides share the three claimed dimensions in their approved tags and mechanisms. Elafin targets neutrophil serine proteases and provides antimicrobial/tissue protection via protease inhibition and NF-κB modulation. Imunofan enhances phagocytic/bactericidal activity and tissue repair via thymopoietin receptor signaling and antioxidant pathways. Their mechanisms are distinct (protease inhibition vs. immune cell activation) yet both contribute to innate immunity, anti-inflammatory effects, and tissue repair. The 'complementary' relationship is justified: they operate through different pathways (Elafin: direct protease inhibition; Imunofan: immune cell enhancement and redox balance) to achieve overlapping functional outcomes in immune defense and tissue homeostasis.

    Shares innate immune · anti inflammatory · tissue repair

  • LactoferrinComplementary

    May be complementary

    Lactoferrin defends by sequestering iron away from microbes and calming inflammation, while elafin blocks neutrophil serine proteases. They are two arms of innate mucosal immunity working through different mechanisms toward the same goal of infection control and reduced inflammatory tissue damage.

    Tier 3Largely anecdotal — commonly discussed

    What the research doesn't fully establish

    Both peptides' mechanisms clearly establish the three claimed shared dimensions. (1) Innate_immune: Elafin targets neutrophil elastase and proteinase 3 (neutrophil serine proteases) and modulates NF-κB and IRF3/IFN-β antiviral signalling; Lactoferrin modulates inflammatory, humoral and cellular immune responses and has antiviral activity. (2) Antimicrobial: Elafin has documented antimicrobial activity against bacteria and fungi; Lactoferrin has broad-spectrum antimicrobial activity (antibacterial, antifungal). (3) Anti_inflammatory: Elafin is explicitly tagged anti_inflammatory with NF-κB pathway modulation; Lactoferrin is explicitly tagged anti_inflammatory with modulation of inflammatory immune responses. The explanation accurately describes their distinct mechanisms (iron sequestration vs. protease inhibition) converging on mucosal defense, which is consistent with the 'complementary' relationship type and the mechanisms provided. The proposed relationship is well-justified by the material.

    Shares innate immune · antimicrobial · anti inflammatory

  • KlothoComplementary

    No documented conflict

    Both suppress NF-κB-driven inflammation and have antifibrotic/vascular-protective roles; Klotho works through FGF23/Nrf2/NLRP3 pathways while elafin works by inhibiting proteases and modulating vascular remodeling. Different upstream mechanisms with overlapping anti-inflammatory, antifibrotic output.

    Tier 4Theoretical — not established

    What the research doesn't fully establish

    Both peptides' mechanisms clearly establish anti-inflammatory and NF-κB modulation as shared dimensions. Elafin explicitly modulates NF-κB pathway (src-17, src-23) and inhibits neutrophil serine proteases with anti-inflammatory effects. Klotho explicitly targets NF-κB signaling and NLRP3 inflammasome with anti-inflammatory activity. The explanation correctly identifies that they achieve these overlapping anti-inflammatory outputs through distinct upstream mechanisms (elafin via protease inhibition and tissue protection; klotho via FGF23/Nrf2/NLRP3 pathways), which is the hallmark of a complementary relationship. Both mechanisms support the claimed shared dimensions and the complementary characterization.

    Shares anti inflammatory · NF kB modulation

  • VilonComplementary

    No documented conflict

    Vilon is an immunomodulatory bioregulator that suppresses inflammatory cytokines and normalizes immune ratios, overlapping with elafin's anti-inflammatory NF-κB modulation but acting through different (gene-regulatory) mechanisms.

    Tier 4Theoretical — not established

    What the research doesn't fully establish

    Both peptides' mechanisms establish the three claimed shared dimensions: (1) innate_immune—Elafin inhibits neutrophil serine proteases and modulates immune responses; Vilon stimulates cellular immunity and improves innate immune markers. (2) anti_inflammatory—Elafin is explicitly tagged anti_inflammatory with NF-κB pathway modulation; Vilon suppresses IL-1β/IL-6/TNF-α cytokines in inflammatory models. (3) NF_kB_modulation—Both peptides' mechanisms explicitly reference NF-κB pathway modulation (Elafin: src-17, src-23; Vilon: IGF1/FOXO1/TERT/NFkB gene expression modulation). The explanation correctly identifies that they share these functional dimensions but operate through distinct mechanisms: Elafin via protease inhibition and direct signaling modulation, Vilon via gene-promoter DNA binding and chromatin remodeling. This constitutes a valid complementary relationship—overlapping functional outcomes achieved through mechanistically different pathways.

    Shares innate immune · anti inflammatory · NF kB modulation

  • MatrixylComplementary

    May be complementary

    Matrixyl stimulates collagen and ECM production while inhibiting matrix-degrading proteases; elafin adds antiprotease protection of elastin/collagen by blocking neutrophil elastase. Complementary matrix-building plus matrix-protecting actions in skin repair.

    Tier 4Theoretical — not established

    What the research doesn't fully establish

    Both peptides' mechanisms clearly support complementary roles in dermal matrix maintenance and tissue repair. Elafin inhibits neutrophil elastase, proteinase 3, and cathepsin G—proteases that degrade collagen and elastin—providing matrix protection. Matrixyl stimulates collagen I/III/IV synthesis and inhibits MMPs and plasmin, providing matrix building and degradation prevention. The mechanisms establish distinct but complementary actions: Elafin protects existing matrix from serine protease degradation while Matrixyl actively synthesizes new matrix and inhibits other matrix-degrading pathways. Both peptides are tagged with dermal_matrix and tissue_repair, and their target mechanisms (antiprotease activity vs. anabolic ECM stimulation) directly support the claimed complementary relationship in skin repair contexts.

    Shares dermal matrix · tissue repair

  • Palmitoyl Tetrapeptide-7Complementary

    No documented conflict

    Both protect the extracellular matrix and dampen inflammation, but by non-overlapping mechanisms — Elafin blocks destructive serine proteases (elastase, proteinase 3) and modulates NF-κB, whereas Palmitoyl Tetrapeptide-7 suppresses IL-6/IL-1β and inhibits MMP-1-driven collagen breakdown. Together they cover a broader range of matrix-degrading enzymes and inflammatory drivers.

    Tier 4Theoretical — not established

    What the research doesn't fully establish

    Both peptides' mechanisms clearly support the proposed complementary relationship on the shared dimensions of dermal_matrix and anti_inflammatory. Palmitoyl Tetrapeptide-7 protects ECM via IL-6/IL-1β suppression and MMP-1 inhibition, while Elafin protects ECM via serine protease inhibition (elastase, proteinase 3) and NF-κB modulation. These are mechanistically distinct pathways targeting different classes of matrix-degrading enzymes and inflammatory mediators. The explanation accurately reflects the non-overlapping mechanisms described in both peptides' material, making them genuinely complementary rather than redundant.

    Shares dermal matrix · anti inflammatory

  • Palmitoyl Tripeptide-1Complementary

    May be complementary

    In a skin-matrix context these are complementary: palmitoyl tripeptide-1 (Pal-GHK) stimulates collagen/elastin synthesis and suppresses MMPs, while elafin protects the dermal matrix by inhibiting elastase and other proteases that degrade elastin. One builds the matrix, the other guards it from enzymatic breakdown.

    Tier 4Theoretical — not established

    What the research doesn't fully establish

    The mechanisms clearly establish complementary roles in dermal matrix maintenance. Elafin inhibits neutrophil elastase, proteinase 3, cathepsin G, and endogenous vascular elastase—all proteases that degrade extracellular matrix components. Palmitoyl Tripeptide-1 stimulates collagen and elastin synthesis while suppressing MMP-1 and other matrix-degrading enzymes. Both peptides are tagged with anti_inflammatory, dermal_matrix, and tissue_repair. The proposed relationship accurately reflects their mechanistic complementarity: one actively synthesizes and protects matrix components (Pal-GHK via TGF-β pathway activation and MMP suppression), while the other protects existing matrix from protease degradation (Elafin via serine protease inhibition). This is a genuine functional complementarity supported by their distinct but synergistic mechanisms.

    Shares anti inflammatory · dermal matrix · tissue repair

  • Alpha-MSHComplementary

    Worth caution

    Elafin protects tissue by inhibiting neutrophil serine proteases and dampening NF-κB, whereas alpha-MSH suppresses inflammation through melanocortin/cAMP signaling and NF-κB. Both also carry antimicrobial activity. These are different upstream mechanisms landing on the same goal of resolving inflammation and protecting mucosal/tissue surfaces, making them a complementary pairing.

    Tier 4Theoretical — not established

    What the research doesn't fully establish

    Both peptides' mechanisms clearly establish the three claimed shared dimensions: (1) Anti-inflammatory: Alpha-MSH suppresses NF-κB via IκBα preservation and uses cAMP/PKA signaling; Elafin modulates NF-κB pathway directly. (2) Antimicrobial: Both explicitly list antimicrobial activity in their effects. (3) NF-κB modulation: Both have this as an approved tag and documented mechanism. The explanation correctly identifies that they achieve these outcomes through distinct upstream mechanisms (melanocortin/cAMP signaling vs. protease inhibition and direct pathway modulation), which is the hallmark of complementarity. The characterization as 'complementary' is justified—they target the same inflammatory/tissue-protective endpoints via different molecular pathways, supporting the proposed relationship type.

    Shares anti inflammatory · antimicrobial · NF kB modulation

Safety and side effects

Safety and Tolerability

Elafin is not approved for human therapeutic use and remains investigational.

  • DrugBank reports that excellent tolerability of elafin in human subjects was demonstrated in a Phase I single-dose escalating study, and lists 1 Phase 1 trial with no Phase 0, 2, 3 or 4 trials.
  • In the 87-patient CABG trial, intravenous elafin 200 mg infusion was reported to be safe.
  • The developer Tiakis reports no safety concerns after treatment of 75 patients in three randomized, double-blind, placebo-controlled clinical trials. This combined safety statement, and the PAH orphan drug designations, are reported by the company rather than an independent source.
  • The Phase I trial (NCT03522935) was designed to assess safety and tolerability via adverse events and their severity, along with pharmacokinetic/pharmacodynamic and immunogenicity parameters — indicating immunogenicity is a monitored consideration for this protein therapeutic.

General peptide context

A review (src-14) states that peptides generally demonstrate favorable safety profiles with minimal adverse events and interact with specific receptors for highly selective responses, while noting challenges in stability and delivery. A tier-3 preprint review separately warns of a pervasive gray market of unapproved peptides sold direct-to-consumer with 'research chemical' disclaimers, marketed via social media and not subject to cGMP guidelines or regulatory oversight.

Efficacy caveats relevant to safety framing

The pivotal CABG trial missed its primary endpoint despite strong biomarker effects, and most other disease-specific findings come from in vitro, animal or observational studies. An oxidation study (src-28) further notes that oxidation by myeloperoxidase/H2O2 significantly impairs elafin's ability to inhibit elastase and proteinase 3 in inflammatory settings, which may limit its activity in inflammatory lung disease.

Reconstitution and handling

Dosing

No dose has been established for this compound. Elafin is not approved for human therapeutic use and no regulatory label exists for it, so the figures below are what research sources report — not guidance.

  • The Phase I trial (NCT03522935) planned subcutaneous administration daily for 7 days in healthy subjects, followed over 28 days, at doses of 0.03, 0.06, 0.10, 0.15 and 0.18 mg/kg across 5 groups of 6 subjects each.
  • The 87-patient CABG trial used a single intravenous dose of elafin 200 mg (formulated as a 200 mg concentration solution for IV infusion), administered after induction of anaesthesia and prior to sternotomy. In that trial this produced a >3000-fold increase in plasma elafin and >50% elastase inhibition in the first 24 hours — yet did not reduce myocardial injury over 48 hours.
  • A vendor profile reports that in research settings elafin is typically administered via topical and intravenous routes.

No human trial has established an efficacious dose for any indication.

Pharmacokinetics

  • A vendor profile (tier-3, single source) reports a half-life of approximately 4–8 hours. Other sources describe elafin only as having 'a short half-life' (src-9) without quantification.
  • The Phase I trial planned to measure pharmacokinetic/pharmacodynamic and immunogenicity parameters including AUC0-last in blood.

Preparation notes

Elafin is a recombinant protein/peptide biological (CAS 820211-82-3; reported ~10 kDa mass in src-21) that has been formulated as a solution for intravenous infusion in trial settings and delivered subcutaneously in the Phase I protocol. As with other protein therapeutics, immunogenicity is a monitored parameter. Reconstitution and handling specifics for any research material should follow the supplier's documentation; no standardized preparation protocol is established for unapproved use.

Sources

Ordered by evidence quality — the strongest first.

  1. Clinical Trials Register(opens in a new tab)
    Tier 1Web · clinicaltrialsregister.eu
  2. EudraCT Number 2010-019527-58 - Clinical trial results - EU Clinical Trials Register(opens in a new tab)
    Tier 1Web · clinicaltrialsregister.eu
  3. NCT03522935 | Subcutaneous Elafin in Healthy Subjects(opens in a new tab)
    Tier 1Web · clinicaltrials.gov
  4. Therapeutic potential of human elafin - PubMed(opens in a new tab)
    Tier 1Web · pubmed.ncbi.nlm.nih.gov
  5. tiakis (formerly Proteo Biotech AG) Elafin Enters the Clinic For Subcutaneous Use In Pulmonary Arterial Hypertension - Tiakis Biotech(opens in a new tab)
    Tier 1Web · tiakis.bio
  6. Elafin level in lichen planus.(opens in a new tab)
    Tier 1PubMed · pubmed.ncbi.nlm.nih.gov · 2024
  7. Perioperative elafin for ischaemia-reperfusion injury during coronary artery bypass graft surgery: a randomised-controlled trial - Glasgow Caledonian University(opens in a new tab)
    Tier 1Web · researchonline.gcu.ac.uk · 2015
  8. Perioperative elafin for ischaemia-reperfusion injury during coronary artery bypass graft surgery: a randomised-controlled trial(opens in a new tab)
    Tier 1Web · doi.org · 2015
  9. Perioperative elafin for ischaemia-reperfusion injury during coronary artery bypass graft surgery: a randomised-controlled trial - University of Edinburgh Research Explorer(opens in a new tab)
    Tier 1Web · research.ed.ac.uk · 2015
  10. Secretory leukocyte protease inhibitor and elafin/trappin-2: versatile mucosal antimicrobials and regulators of immunity.(opens in a new tab)
    Tier 1PubMed · pubmed.ncbi.nlm.nih.gov · 2010
  11. Elafin (SKALP/Trappin-2/proteinase inhibitor-3) is produced by the cervix in pregnancy and cervicovaginal levels are diminished in bacterial vaginosis.(opens in a new tab)
    Tier 1PubMed · pubmed.ncbi.nlm.nih.gov · 2009
  12. The serine protease inhibitor trappin-2 is present in cartilage and synovial fluid in osteoarthritis.(opens in a new tab)
    Tier 1PubMed · pubmed.ncbi.nlm.nih.gov · 2006
  13. Elafin and its precursor trappin‐2: What is their therapeutic potential for intestinal diseases?(opens in a new tab)
    Tier 2Web · pmc.ncbi.nlm.nih.gov
  14. Elafin Reverses Intestinal Fibrosis by Inhibiting Cathepsin S-Mediated ...(opens in a new tab)
    Tier 2Web · cmghjournal.org
  15. Elafin: Uses, Interactions, Mechanism of Action(opens in a new tab)
    Tier 2Web · go.drugbank.com
  16. Safety and Efficacy of Peptide-Based Therapeutics in Health Sciences(opens in a new tab)
    Tier 2Web · biomedgrid.com
  17. Elafin and its precursor trappin-2: What is their therapeutic potential for intestinal diseases?(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2023
  18. Endogenous Retroviral Elements Generate Pathologic Neutrophils in Pulmonary Arterial Hypertension.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2022
  19. NOD2 signalling in hidradenitis suppurativa.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2021
  20. A potential contribution of trappin-2 to the development of vasculopathy in systemic sclerosis.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2019
  21. Antiviral activity of trappin-2 and elafin in vitro and in vivo against genital herpes.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2013
  22. The WAP protein Trappin-2/Elafin: a handyman in the regulation of inflammatory and immune responses.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2012
  23. Secretory leukocyte protease inhibitor (SLPI) is, like its homologue trappin-2 (pre-elafin), a transglutaminase substrate.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2011
  24. Trappin-2/Elafin: a novel innate anti-human immunodeficiency virus-1 molecule of the human female reproductive tract.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2010
  25. Oxidized elafin and trappin poorly inhibit the elastolytic activity of neutrophil elastase and proteinase 3.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2005
  26. Proteolytic susceptibility of the serine protease inhibitor trappin-2 (pre-elafin): evidence for tryptase-mediated generation of elafin.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2005
  27. Antimicrobial activity of antiproteinases.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2002
  28. Elafin | Peptide United(opens in a new tab)
    Tier 3Web · peptideunited.com
  29. Safety and Efficacy of Approved and Unapproved Peptide Therapies for ...(opens in a new tab)
    Tier 3Web · preprints.org
  30. Peptide Half-Life Explained: Duration, Stability, and Research Protocols (UK 2026) - Peptides Lab UK(opens in a new tab)
    Tier 4Web · peptideslabuk.com