Before you inject, read what the trials actually said.

Semaglutide is a GLP-1 receptor agonist with the most extensive Phase 3 trial program of any compound in this research series. Available as subcutaneous injection (Ozempic, Wegovy) and oral tablet (Rybelsus, oral Wegovy). Phase 3 STEP trials demonstrated 14.9-17.4% weight loss at 68 weeks. The SELECT trial (n=17,604) demonstrated 20% MACE reduction in non-diabetic obesity with CVD. The FLOW trial (n=3,534) demonstrated 24% reduction in major kidney disease events. The ESSENCE trial (n=800 interim) achieved 62.9% MASH resolution at 72 weeks leading to accelerated FDA approval. Oral Wegovy 25mg approved December 2025 as the first oral GLP-1 for weight management.

Tirzepatide is a single synthetic molecule that simultaneously agonizes both the GIP and GLP-1 receptors -- the only approved dual incretin agonist. SURMOUNT-1 (n=2,539) demonstrated 20.9% mean weight loss at 72 weeks with 15mg dose, and sustained 22.9% at 176 weeks (3 years). SURMOUNT-5 head-to-head vs semaglutide: 20.2% vs 13.7% -- 47% greater relative weight reduction. First medication ever approved for obstructive sleep apnea (December 2024). SURPASS-CVOT (NEJM December 2025, n=13,299): noninferior to dulaglutide for MACE, 16% lower all-cause mortality, greater kidney protection.

Survodutide (BI 456906) is an investigational once-weekly subcutaneous peptide that acts as a dual agonist at both the glucagon receptor (GCGR) and the GLP-1 receptor (GLP-1R). In Phase 2 trials, it produced up to 18.7% weight loss at 46 weeks (completers; 4.8 mg dose) versus 2.3% placebo (Le Roux et al. 2024, Lancet Diabetes Endocrinology; n=386). In a separate Phase 2 MASH trial, 62% of participants receiving 4.8 mg achieved histologic MASH resolution without worsening fibrosis versus 14% placebo (Sanyal et al. 2024, NEJM; n=293; 48 weeks). The FDA granted Breakthrough Therapy designation for MASH in September 2024. Phase 3 SYNCHRONIZE trials (obesity) and LIVERAGE trials (MASH) are fully enrolled; results expected H1 2026. The primary safety concern is GI tolerability: 25% of survodutide recipients discontinued due to AEs (mostly GI) versus 4% placebo.

TB4 (full 43-AA) is an endogenous actin-binding peptide with genuine Phase 2 clinical evidence in ophthalmology and wound healing. TB-500 is a synthetic 7-AA fragment with no human trial data. The most sought-after application (musculoskeletal repair) has zero human evidence for either compound. TB-500 was FDA de-listed in September 2024. Both are WADA banned.

BPC-157 is a 15 amino acid peptide isolated from human gastric juice with over 500 preclinical publications spanning 30 years, and fewer than 30 humans studied in published trials. Its strongest evidence is in GI healing, where it has reached Phase II trial exposure in Croatia. FDA Category 2 status (2023) prohibits commercial compounding in the United States.

KPV is a tripeptide comprising the C-terminal three amino acids of alpha-MSH (alpha-melanocyte stimulating hormone). It captures most of the parent hormone's anti-inflammatory activity through intracellular NF-kB inhibition and NLRP3 inflammasome suppression without engaging its melanogenic or hormonal effects. Its most scientifically distinctive property is PepT1-mediated oral uptake, selectively upregulated in inflamed colonic tissue in IBD, creating inherent disease-site targeting. All evidence is preclinical: no completed human clinical trials exist for any indication.

Afamelanotide (SCENESSE) is the first FDA-approved alpha-MSH analogue, indicated for increasing pain-free light exposure in adults with erythropoietic protoporphyria (EPP). A selective MC1R agonist delivered as a subcutaneous bioresorbable implant every two months, it stimulates eumelanin production without UV-induced cellular damage. Two Phase 3 RCTs (n=244 pooled) demonstrated 56% more pain-free sunlight hours and an 8-fold difference in outdoor pain-free time versus placebo. A Phase 3 vitiligo trial (CUV105, n=200 fully enrolled) has topline results expected second half 2026.

Bremelanotide (PT-141/Vyleesi) is an FDA-approved cyclic melanocortin analogue that acts centrally via MC4R on dopaminergic and noradrenergic sexual arousal pathways, the only approved HSDD treatment that works through the brain's sexual desire circuitry rather than vascular or monoamine mechanisms. Approved 2019 as the first as-needed treatment for female HSDD (versus daily flibanserin). Phase 2 data supports off-label use in male erectile dysfunction non-responsive to PDE5 inhibitors; combination bremelanotide plus PDE5i product in active Phase 2 development by Palatin.

Liraglutide is the first long-acting GLP-1 receptor agonist, a once-daily subcutaneous injection with 97% homology to human GLP-1. The SCALE program demonstrated 8.0% mean weight loss at 56 weeks. The LEADER trial (n=9,340) demonstrated 13% MACE reduction and significant cardiovascular death and all-cause mortality reduction in T2D. Now available as the first generic GLP-1 for weight loss (August 2025). Largely superseded by semaglutide and tirzepatide for new prescriptions, but retains relevance as the most affordable GLP-1 option with the longest safety track record.

Orforglipron (Foundayo) is the first non-peptide, oral small-molecule GLP-1 receptor agonist approved for weight management. FDA approved April 1, 2026. A once-daily pill taken without food or water restrictions. ATTAIN-1 (n=1,686, 72 weeks): 12.4% weight loss at highest dose. ATTAIN-2 (n=1,078, T2D): 10.5% weight loss, 1.8% HbA1c reduction. Superior to oral semaglutide on HbA1c in head-to-head ACHIEVE-3. ATTAIN-MAINTAIN: maintained weight loss in patients switching from injectable Wegovy/Zepbound. Less potent than injectable GLP-1s but eliminates injection and fasting barriers. Self-pay $149/month; $25/month with insurance.

Pramlintide (Symlin) is the only FDA-approved amylin analogue, approved in 2005 as an adjunct to mealtime insulin for type 1 and type 2 diabetes. It proved the amylin pathway is druggable in humans: slowing gastric emptying, suppressing postprandial glucagon, and reducing meal size through brainstem satiety signaling. In clinical trials, pramlintide reduced HbA1c by 0.2 to 0.6% and produced weight loss of 1 to 3 kg in diabetic populations, modest but meaningful given that insulin typically causes weight gain. In obesity trials without diabetes, weight loss reached 3.7 to 6.8% at higher doses. The critical limitation is pharmacokinetic: a half-life of approximately 48 minutes requires injection before every major meal (2 to 3 times daily), the same dosing burden as rapid-acting insulin. This dosing frequency severely limited clinical adoption and motivated the development of cagrilintide, a once-weekly amylin analogue now under FDA review as part of CagriSema.

Tesamorelin (EGRIFTA) is the only FDA-approved GHRH analogue, approved since 2010 for HIV-associated lipodystrophy, with a March 2025 approval of the once-weekly EGRIFTA WR formulation. Two Phase 3 RCTs (n=806) established 15 to 20% selective visceral fat reduction. NIH-funded off-label research shows compelling MASLD liver fat reduction (35% complete resolution at 12 months), cognitive function improvements, and skeletal muscle benefits.

Cagrilintide is a once-weekly injectable amylin analogue developed by Novo Nordisk that activates both amylin and calcitonin receptors to produce satiety and reduce food intake. In Phase 3 REDEFINE 1 (n=3,417), cagrilintide combined with semaglutide achieved 20.4% mean body weight loss at 68 weeks versus 3.0% with placebo. Monotherapy produced 11.8% weight loss in the same trial. An NDA for the CagriSema combination was filed with the FDA in December 2025.

CagriSema is a fixed-dose combination of cagrilintide 2.4 mg (long-acting amylin analogue) and semaglutide 2.4 mg (GLP-1 receptor agonist), once weekly subcutaneous. REDEFINE 1 (n=3,417, 68 weeks): 20.4% weight loss (ITT) vs 3.0% placebo, exceeding semaglutide alone (14.9%) by 5.5 points. REDEFINE 2 (n=1,206, T2D): 15.7% weight loss. REDEFINE 4 head-to-head vs tirzepatide 15 mg (n=809, 84 weeks, open-label): CagriSema 23% vs tirzepatide 25.5%, noninferiority not met. NDA filed December 2025, decision expected late 2026. If approved, would be the first GLP-1/amylin combination product.

Gonadorelin is a synthetic decapeptide identical in sequence to endogenous gonadotropin-releasing hormone (GnRH), the hypothalamic master regulator of the reproductive axis. It stimulates pituitary release of LH and FSH, which in turn drive gonadal steroidogenesis and gametogenesis. FDA-approved formulations existed for diagnostic use and pulsatile ovulation induction but are commercially discontinued; compounding remains active. Its primary documented clinical utility is pulsatile pump delivery for hypothalamic amenorrhea (70 to 100% pregnancy rates in responsive cases) and spermatogenesis induction in CHH. The dominant current community use as a daily subcutaneous injection TRT adjunct lacks pharmacokinetic rationale given gonadorelin's 10 to 40 minute half-life.

Mazdutide is the world's first approved dual glucagon/GLP-1 receptor agonist. GLORY-1 Phase 3 (n=610, NEJM): 14.0% mean weight loss at 48 weeks with 6 mg dose. GLORY-2 (9 mg): 20.1% weight loss. DREAMS-1 and DREAMS-2 (Nature): superiority to dulaglutide in T2D. Liver fat reduction up to 80% (MRI-PDFF). Approved in China, not FDA-approved. All Phase 3 data from exclusively Chinese populations.

Retatrutide (LY3437943) is a purpose-engineered triple agonist targeting GLP-1, GIP, and glucagon receptors, developed by Eli Lilly. It is the most clinically advanced compound in this research series and has produced the highest weight loss ever documented in a pharmaceutical trial (28.7% at 68 weeks in Phase 3). The TRIUMPH Phase 3 program covers 8 indications in 5,800+ patients across 13 countries. First readout (TRIUMPH-4, December 2025) met all primary and key secondary endpoints.

SS-31 (elamipretide) is a mitochondria-targeting tetrapeptide that binds cardiolipin in the inner mitochondrial membrane to stabilize energy production and reduce oxidative stress. It received FDA accelerated approval in 2025 for Barth syndrome, making it the first treatment ever approved for this cardiolipin disorder. Multiple Phase 2 trials are underway for heart failure, renal disease, and age-related conditions.

Thymosin Alpha-1 is the most extensively human-studied peptide in this research series: 30+ clinical trials, 11,000+ subjects, and regulatory approvals in 35+ countries. It modulates the immune system via TLR-2/TLR-9 activation to enhance T-cell differentiation and Th1 polarization. Strongest current applications are vaccine adjuvancy in elderly/immunocompromised patients and cancer combination immunotherapy regimens.

ARA 290 (cibinetide) is a synthetic 11-amino acid peptide derived from the tissue-protective helix-B domain of erythropoietin. It is the only peptide in this research series to demonstrate structural nerve regeneration (a 23% increase in GAP-43-positive fibers) in a double-blind RCT. It holds FDA Fast Track and Orphan Drug designations for sarcoidosis-associated neuropathy and has completed a successful end-of-Phase 2 FDA meeting.

Kisspeptin is the endogenous master regulator of the human reproductive axis -- the only peptide whose complete absence causes total reproductive failure in humans. Discovered via KISS1R loss-of-function mutations causing congenital hypogonadotropic hypogonadism, it has 29 completed clinical trials and the most genetically validated mechanism of any compound in this research series. Phase 2 IVF trigger RCTs (n=60 high-OHSS-risk women) achieved 95% oocyte maturation and 45% live birth rate with zero OHSS at any dose. A 2025 eBioMedicine paper established intranasal delivery as a viable non-invasive route, potentially transforming all kisspeptin applications from hospital IV infusion to patient self-administration.

MK-677 (ibutamoren mesylate) is a non-peptide, orally active agonist of the ghrelin receptor (GHS-R1a) that stimulates endogenous GH and IGF-1 secretion. It is the only oral GH secretagogue with substantial published human trial data, including a 2-year, double-blind, placebo-controlled RCT (Nass et al. 2008, Annals of Internal Medicine, n=65). That trial showed significant FFM preservation and GH axis restoration in older adults, with meaningful metabolic liabilities: worsened insulin sensitivity, increased fasting glucose, and no functional strength improvement. A Phase 2b hip fracture trial (Adunsky 2011, n=123) was terminated early for a congestive heart failure signal. An Alzheimer's disease trial (Sevigny 2008, n=563) showed zero cognitive benefit despite a 72.9% IGF-1 increase. The same molecule is now in Phase 3 pediatric GHD development as LUM-201 (Lumos Pharma), with Phase 2 data showing 8.2 cm/yr height velocity comparable to rhGH.

NAD+ (nicotinamide adenine dinucleotide) is the coenzyme at the center of cellular energy metabolism, DNA repair, and sirtuin-mediated aging regulation. NAD+ levels decline approximately 50% between ages 40 and 60 through multiple mechanisms including increased CD38-mediated degradation and reduced NAMPT-driven synthesis. Two oral precursors -- NMN and NR -- have the most robust human clinical evidence: NMN published in Science (Yoshino et al. 2021, n=25) showed increased muscle insulin sensitivity; NR published in Nature Communications (McDermott et al. 2024, NICE trial, n=90) improved 6-minute walk distance in peripheral artery disease by 17.6 meters vs. placebo. The human evidence base is genuinely positive but limited: trials are short (10 to 12 weeks), small (n=20 to 90), and have produced inconsistent results on functional endpoints. Injectable NAD+ (IV and subcutaneous) is widely used in wellness settings despite a fundamental scientific dispute over whether the NAD+ molecule -- too large and charged to enter cells directly -- actually delivers benefit via the proposed cellular mechanism.

Sermorelin (GHRH 1-29) is the only compound in this research series with a history of full FDA approval, voluntarily discontinued for commercial reasons in 2008. It stimulates endogenous GH release via pituitary GHRH receptors with a built-in somatostatin safety ceiling. Human evidence includes the approved pediatric GHD indication, small but consistent adult aging body composition data, and replicated cognitive function improvements in aging and MCI from the University of Washington research program.

Argireline (Acetyl Hexapeptide-8) is a synthetic cosmetic hexapeptide developed by Lipotec in 2002, designed to mimic the N-terminal end of SNAP-25 and competitively inhibit SNARE complex formation at the neuromuscular junction, reducing facial muscle contraction and expression wrinkles. The cellular mechanism is confirmed in vitro. The Wang 2013 RCT (n=60) showed 48.9% subjective wrinkle improvement versus 0% placebo at 4 weeks. However, the Kraeling 2015 in vitro penetration study (conducted at FDA laboratories) found zero Argireline detectable in human skin dermis after topical application. Whether wrinkle improvements reflect the claimed neuromuscular mechanism or surface hydration effects is an unresolved scientific controversy. All major clinical studies were conducted by or affiliated with Lipotec.

CJC-1295 is a synthetic GHRH analogue developed by ConjuChem Biotechnologies in two forms: CJC-1295 with DAC (half-life 6-8 days, weekly dosing, albumin-binding) and CJC-1295 without DAC / Modified GRF 1-29 (half-life approximately 30 minutes, pulsatile GH release). The primary human evidence is the Teichman 2006 Phase 1 RCT (JCEM) confirming 2-10 fold GH increases and 1.5-3 fold IGF-1 increases sustained for up to 28 days in healthy adults. The pharmaceutical development program was terminated after a Phase 2 death in 2006. It is the most widely used GH secretagogue in research protocols, typically combined with ipamorelin.

Collagen peptides are not a single defined molecule. They are a heterogeneous mixture of short peptide fragments (typically 2 to 20 amino acids) produced by enzymatic hydrolysis of animal collagen from bovine, marine, porcine, or chicken sources. This profile exists because collagen peptides are the single most searched peptide category globally and because readers deserve an evidence-based assessment rather than supplement marketing copy. The evidence: multiple meta-analyses of RCTs (totaling 1,400 to 1,700 participants) show statistically significant improvements in skin hydration and elasticity. However, a 2025 American Journal of Medicine meta-analysis (23 RCTs, n=1,474) found that when restricted to non-industry-funded and high-quality studies, the effects disappear entirely. For joints, Clark 2008 (n=147, 24 weeks) and subsequent RCTs show modest pain reduction in athletes. For muscle, Zdzieblik 2015 (n=53, 12 weeks) showed improved lean mass in sarcopenic elderly men with resistance training. The evidence is real but modest, conflicted by industry funding, and substantially overhyped by the supplement industry.

Follistatin is an endogenous glycoprotein that neutralizes multiple TGF-beta superfamily members including myostatin (GDF-8), activin A/B, and GDF-11, removing the primary molecular brakes on skeletal muscle growth. Transgenic mice overexpressing follistatin show muscle mass increases of 194 to 327% above controls -- effects exceeding even myostatin knockout animals. Two Phase 1/2a human gene therapy trials using AAV1-FS344 have been completed: one in Becker muscular dystrophy (BMD; n=6, Mendell 2015, Molecular Therapy) and one in sporadic inclusion body myositis (sIBM; n=6, Mendell 2017, Molecular Therapy). Both showed functional improvements and biopsy evidence of benefit but were open-label, uncontrolled, n=6 proof-of-concept trials whose efficacy conclusions have been critically challenged in the published literature. The injectable protein form used in the biohacking community has a ~90-minute half-life, no validated human dosing protocol, and a documented case series of central serous chorioretinopathy at high doses.

GHK-Cu is a naturally occurring human tripeptide that declines with age and holds the strongest validated human evidence in this series for skin and wound healing applications. It is the only peptide reviewed here with mass-scale, multi-decade topical clinical use. Independent Broad Institute bioinformatic analysis found GHK tops 1,309 bioactives for reversing COPD and metastatic colon cancer gene expression, though no human trials in those domains have been conducted.

GHRP-2 (pralmorelin) is a synthetic hexapeptide GHS-R1a agonist and the most potent traditional GH-releasing peptide. It is the only GH secretagogue with regulatory approval anywhere in the world -- approved in Japan since 2004 as a diagnostic agent for GH deficiency. Unlike the more selective ipamorelin, GHRP-2 also elevates cortisol and prolactin at therapeutic doses, a distinguishing pharmacological liability. A negative 48-week intranasal growth trial in 126 GH-deficient children found no benefit on height SD score.

Hexarelin (examorelin) is a synthetic hexapeptide GH secretagogue developed by Mediolanum Farmaceutici. It is the most potent traditional GHRP for acute GH release -- exceeding maximal GHRH -- and uniquely binds both GHS-R1a and cardiac CD36 receptors. Three human cardiac studies demonstrate acute GH-independent improvements in left ventricular ejection fraction in healthy volunteers (n=7), GH-deficient patients, coronary artery disease patients (n=24), and severe cardiomyopathy patients (n=13). The defining practical limitation is pronounced tachyphylaxis: GH response attenuates 50 to 75% within weeks of daily use. Phase 2 development reached for GH deficiency and congestive heart failure but was discontinued in 2005 for commercial rather than safety reasons.

LL-37 is the only cathelicidin produced by the human genome, derived from the precursor protein hCAP18. It is a front-line innate immune peptide deficient in chronic wounds (venous leg ulcers, diabetic foot ulcers) but present in normal acute wounds. Two Phase 2 RCTs (n=34 and n=144) established topical LL-37 as safe and wound-healing efficacious, with the clearest benefit in large ulcers (10 cm2 or larger). No Phase 3 data exist. Published preclinical evidence documents pro-tumorigenic activity in ovarian, lung, breast, prostate, and melanoma contexts, and a role as a T-cell autoantigen in psoriasis and SLE, constituting mandatory safety disclosures for any research context.

Matrixyl (Palmitoyl Pentapeptide-4, Pal-KTTKS) is a synthetic lipopeptide cosmetic ingredient developed by Sederma (France) that mimics matrikine signaling to stimulate collagen synthesis in dermal fibroblasts. The largest clinical trial (Robinson 2005, n=93, 12 weeks, split-face RCT) showed statistically significant wrinkle reduction versus placebo moisturizer. All significant clinical trials were industry-funded. No independently funded academic replication exists. Matrixyl 3000 (a second-generation combination of Palmitoyl Tripeptide-1 and Palmitoyl Tetrapeptide-7) extends the mechanism to include anti-inflammatory signaling. No injectable or systemic formulation exists or has been studied.

Omiganan is a synthetic 12-amino acid cationic peptide derived from indolicidin, an antimicrobial peptide from bovine neutrophil granules. It shares the cathelicidin protein family with the human peptide LL-37 (profiled separately), but its direct structural parent is the bovine indolicidin, not LL-37. Omiganan has the broadest clinical trial record of any synthetic antimicrobial peptide: Phase 3 for catheter infection prevention (missed primary endpoint) and papulopustular rosacea (statistically significant vs. vehicle), Phase 2 for acne vulgaris (positive), atopic dermatitis (microbiome recovery without clinical improvement), seborrheic dermatitis (negative vs. placebo), and HPV-induced anogenital lesions (96.6% HPV viral load reduction in anogenital warts, p=0.045). No indication has achieved regulatory approval.

Oxytocin is an endogenous nonapeptide hormone synthesized in the hypothalamus with FDA-approved obstetric uses. Intranasal oxytocin for behavioral indications has been extensively studied but has not achieved regulatory approval for any social, cognitive, or psychiatric indication. The largest RCT to date -- Sikich et al. (2021, NEJM), n=290 children with autism, 24 weeks -- was fully negative on the primary endpoint (ABC-mSW difference: -0.2, p=0.61). Acute single-dose studies in healthy adults consistently show small improvements in emotion recognition, but chronic treatment trials have failed to replicate these effects on clinical outcomes.

AOD-9604 is a synthetic 16-amino acid fragment of the C-terminus of human growth hormone (hGH residues 176 to 191), developed at Monash University in the 1990s as a selective anti-obesity drug. Six human clinical trials involving approximately 900 participants established a clean safety profile. A Phase IIa trial (n=300, 12 weeks) showed 2.6 to 2.8 kg additional weight loss at 1 mg/day versus 0.8 kg placebo. The pivotal Phase IIb OPTIONS trial (n=536, 24 weeks) failed to replicate this finding at any dose. Development was terminated in 2007. Cannot be legally compounded in the United States as of March 2026.

Davunetide (NAP, AL-108, CP201) is a synthetic octapeptide (NAPVSIPQ) derived from activity-dependent neuroprotective protein (ADNP). It promotes microtubule stability and inhibits tau hyperphosphorylation. The largest human trial, Boxer et al. (2014, Lancet Neurology), was a well-powered Phase 2/3 RCT in 313 PSP patients at 48 international centers that was fully negative on all primary, secondary, and exploratory endpoints. The trial authors concluded: davunetide is not an effective treatment for PSP. A Phase 2a MCI signal exists only as a conference abstract. Post-hoc sex-stratified re-analyses of the failed PSP trial, conducted by the compound's inventor, are hypothesis-generating only.

Delta Sleep-Inducing Peptide (DSIP) is a 9-amino-acid endogenous neuropeptide first isolated in 1974 from the cerebral venous blood of sleeping rabbits by the Schoenenberger-Monnier group in Switzerland. Despite its name suggesting a clear mechanism, DSIP's sleep-promoting effects in humans have been contradictory across 40-plus years of research: some controlled trials showed modest sleep improvements, while the most rigorous study (Schneider-Helmert 1992, n=16, double-blind) concluded that short-term treatment of chronic insomnia was not likely to be of major therapeutic benefit. The compound's most compelling human clinical data are actually in addiction medicine: a 1984 uncontrolled study of n=107 inpatients (n=47 alcohol withdrawal, n=60 opiate withdrawal) reported benefits in 97% of opiate-dependent and 87% of alcohol-dependent patients with IV DSIP. In mouse lifespan studies, a DSIP-containing preparation (Deltaran) extended maximum lifespan by 24.1% and reduced spontaneous tumor incidence 2.6-fold. No receptor or precursor gene for DSIP has been identified in 50 years of research.

Epithalon is a synthetic tetrapeptide (Ala-Glu-Asp-Gly) derived from the bovine pineal gland. Its primary scientific focus is telomere biology: it activates telomerase and may induce ALT pathway activity in cell culture. All clinical data originates from a single Russian research group with no Western independent replication until the 2025 Biogerontology study. The entire evidence base must be interpreted with this structural limitation in mind.

FGL is a synthetic 15-amino acid peptide derived from the FG loop region of the second fibronectin type III module of NCAM (neural cell adhesion molecule). It acts as a selective FGFR1 agonist, promoting synaptogenesis, LTP, neurogenesis, and neuroprotection in preclinical models. A Phase 1 study in 24 healthy males confirmed tolerability and CNS penetration via intranasal administration. No efficacy trials in patients have produced published results despite a funded clinical program announced in 2012.

GHRP-6 is the original growth hormone releasing peptide, synthesized by Cyril Bowers and colleagues at Tulane University in 1984 as the first synthetic peptide to specifically and dose-dependently release GH through a receptor mechanism entirely distinct from GHRH. Its pharmacological characterization generated the field of GH secretagogue research, identified GHS-R1a as a receptor class, and ultimately enabled the discovery of ghrelin in 1999. Human Phase 1 data from Bowers et al. (1990, n=18) established dose-dependent GH release: mean peak GH of 68.7 plus or minus 15.5 mcg/L at 1.0 mcg/kg IV. GHRP-6's defining clinical characteristic is its stronger appetite stimulation than any other GHRP -- a pharmacological certainty from GHS-R1a activation, not an individual side effect. It has been superseded for most applications by ipamorelin (cleaner endocrine profile) and GHRP-2 (greater GH potency), but remains the historically foundational compound of the class.

Humanin is a 24-amino acid mitochondria-derived peptide (MDP) encoded within the 16S rRNA gene (MT-RNR2) of mitochondrial DNA, discovered in 2001 simultaneously by three independent research groups. It is the founding member of the MDP family, which also includes MOTS-c and the SHLP peptides. Humanin has documented cytoprotective and neuroprotective effects across dozens of preclinical studies using cell culture and animal models. Human data is limited to observational biomarker studies: circulating humanin declines with age, is elevated in children of centenarians, and is associated with preserved coronary endothelial function. No human intervention trial of any kind has been completed. No IND has been filed. All dosing in community use is extrapolated from animal models without clinical validation.

Ipamorelin is a selective GHS-R1a (ghrelin receptor) agonist and the first GH secretagogue documented not to stimulate ACTH or cortisol even at 200x therapeutic doses. Its only completed published human RCT -- a Phase 2 trial for postoperative ileus -- failed its primary endpoint (P=0.15), ending the pharmaceutical development program. All body composition and anti-aging claims are extrapolations from GH biology with no direct human trial evidence.

Melanotan II (MT-II) is a synthetic cyclic lactam analog of alpha-melanocyte-stimulating hormone, developed in the late 1980s at the University of Arizona. It is the parent compound from which bremelanotide (PT-141, FDA-approved for HSDD) was derived. MT-II has Phase 1 and small Phase 2 human data demonstrating reliable skin tanning (Dorr et al., 1996) and potent erectogenic effects (Wessells et al., 1998 and 2000). Clinical development was formally abandoned due to the combination of severe nausea side effects and melanoma safety concerns. It is now sold exclusively through unregulated grey markets, a status associated with documented product contamination, dosing inaccuracy, eruptive naevi, and case reports of melanoma.

MOTS-c is the only peptide in this research series encoded by mitochondrial (not nuclear) DNA. A mitochondrial-derived 16-amino acid peptide discovered in 2015, it functions as an exercise-induced signaling molecule that activates AMPK via the folate-methionine cycle. Its CB4211 analog completed a Phase 1b NAFLD trial showing significant liver enzyme and glucose improvement. No human therapeutic trials for MOTS-c itself exist.

Pancragen (Lys-Glu-Asp-Trp, KEDW) is the pancreas-targeted member of the Khavinson bioregulator family, making it uniquely distinctive in this series: it has published indexed human clinical data. A 2011 study in 33 elderly type 2 diabetes patients reported significant fasting glucose reduction, improved glucose tolerance, and reduced insulin resistance index, with no equivalent changes in untreated comparators. Rhesus monkey studies (2014, 2015) demonstrated glucose normalization and improved C-peptide dynamics comparable to glimepiride. Cell culture studies show activation of key pancreatic differentiation transcription factors. No randomized controlled trial has been published, and all human data originate from one institution. The glucose-lowering signal is real enough to warrant serious caution about combining Pancragen with existing antidiabetic medications without medical supervision.

Pinealon (Glu-Asp-Arg, EDR) is a synthetic tripeptide isolated from the polypeptide neuroprotective drug Cortexin and developed by the St. Petersburg Institute of Bioregulation and Gerontology. It is the most clinically supported Khavinson bioregulator other than Pancragen: oral administration in 72 patients with traumatic brain injury consequences (0.2 mg twice daily, 20 to 30 days, with a 37-patient control group) produced improvements in memory, headache reduction, emotional stability, and EEG alpha-index changes. Additional published rodent data include prenatal neuroprotection, hypoxia tolerance, cognitive improvement across aging models, and dendritic spine preservation in Alzheimer's and Huntington's disease cell models. The 2021 MDPI Molecules open-access review provides the most comprehensive mechanistic characterization to date. No randomized controlled trial has been published.

Selank is a synthetic heptapeptide (Thr-Lys-Pro-Arg-Pro-Gly-Pro) developed at the Institute of Molecular Genetics, Russian Academy of Sciences, as a metabolically stabilized analog of tuftsin. It is approved in Russia since 2009 as an intranasal anxiolytic for GAD and neurasthenia. The pivotal clinical study (Zozulya et al., 2008, n=62) compared Selank to medazepam and found comparable anxiolytic efficacy with additional antiasthenic and psychostimulant effects. All human clinical data comes from Russian institutions; no GCP-compliant international trials exist.

Semax is a synthetic heptapeptide (Met-Glu-His-Phe-Pro-Gly-Pro) derived from the ACTH(4-7) N-terminal fragment, stabilized with a Pro-Gly-Pro C-terminal extension. It retains the neurotrophic and neuroprotective properties of ACTH fragments without any adrenocortical hormonal activity. Approved in Russia and Ukraine since the 1990s for stroke, optic nerve disease, and cognitive decline. Human clinical data includes a 30-patient stroke trial (Gusev et al., 1997), a 110-patient BDNF/rehabilitation study (Gusev et al., 2018), and a 24-subject placebo-controlled fMRI study in healthy volunteers (Lebedeva et al., 2018). All evidence is Russian-origin with no Western GCP replication.

SNAP-8 (Acetyl Octapeptide-3) is a synthetic cosmetic octapeptide developed by Lipotec as an extended analog of Argireline, designed to more completely mimic the N-terminal domain of SNAP-25 and improve competitive inhibition of SNARE complex formation. The widely cited '63% wrinkle reduction in 28 days' claim comes from Lipotec's own technical data sheet, not a peer-reviewed publication. No standalone placebo-controlled RCT of topical SNAP-8 exists. The two published human studies are a confounded multi-ingredient microneedle patch trial (Shin 2024, n=24) and an open-label multi-peptide serum with no placebo arm (Draelos 2016, n=29). SNAP-8 has a mechanistically plausible design and clean safety record, but its evidence base is the weakest of any cosmetic peptide profiled in this series.

Thymalin is a polypeptide complex extracted from the thymus glands of young calves, developed by Professors Morozov and Khavinson at the St. Petersburg Institute of Bioregulation and Gerontology beginning in the 1970s. Unlike the synthetic single-sequence Khavinson bioregulators (Epithalon, Pinealon, Vesugen, Pancragen), Thymalin is a multi-component preparation containing short peptides including the dipeptides EW (Glu-Trp, also known as Thymogen) and KE (Lys-Glu, also known as Vilon). The most significant human clinical finding is the indexed Khavinson and Morozov (2002, 2003) long-term observational study in 266 elderly persons (over 60 years), followed 6 to 8 years, which reported a 2.0 to 2.1-fold mortality decrease in Thymalin-treated patients and a 4.1-fold decrease in the group receiving Thymalin combined with Epithalamin annually over 6 years. Thymalin is also the only Khavinson bioregulator with approved Russian pharmaceutical status, with a COVID-19 PMC study in n=36 elderly patients providing the most recent indexed human data.

Vesugen (Lys-Glu-Asp, KED) is a synthetic tripeptide derived from vascular wall protein sequences, developed by Professor Khavinson at the St. Petersburg Institute of Bioregulation and Gerontology. It is the most clinically studied Khavinson bioregulator to cross into human territory: small Russian observational studies in atherosclerosis patients, post-surgical lower limb ischemia cases, and vasculogenic erectile dysfunction report meaningful improvements in vascular endpoints. The mechanistic work, including Ki-67 gene promoter docking, SIRT1 upregulation, and endothelin-1 normalization in endothelial cultures, is more developed than most Khavinson compounds. None of the human studies were randomized, blinded, or placebo-controlled, and all originate from a single research institution.

Zinc thymulin (Zn-FTS) is an endogenous nonapeptide hormone produced by thymic epithelial cells, first characterized by Bach and Dardenne in 1977. It requires zinc binding in a 1:1 ratio for biological activity: without zinc, the peptide is inert. Thymulin's established role is in T-cell differentiation and immune modulation, but its current commercial interest is driven almost entirely by hair loss applications. Meier et al. (2012, Journal of Investigative Dermatology) showed thymulin extends anagen phase in human hair follicle organ culture. A single open-label human trial (Vickers 2017, n=18, 4 to 10 months) reported significant hair growth improvement with topical zinc thymulin spray in androgenetic alopecia. The evidence is promising but extremely preliminary: one small uncontrolled study does not constitute proof of efficacy. Thymulin is distinct from Thymosin Alpha-1 and Thymalin, two other thymic peptides already profiled in this series.

5-Amino-1MQ (5-Amino-1-Methylquinolinium) is a synthetic small molecule NNMT inhibitor, not a peptide, included in this series because it circulates widely in peptide research contexts. NNMT (nicotinamide N-methyltransferase) methylates nicotinamide, depleting NAD+ precursors and consuming SAM. Inhibiting NNMT raises intracellular NAD+, elevates SAM, and suppresses lipogenesis in adipocytes. The Neelakantan 2018 mouse study (11 days, diet-induced obese) showed significant fat mass and body weight reduction without food intake changes. Babula 2024 (28 days, diet-induced obese mice) confirmed dose-dependent fat mass limitation, improved insulin sensitivity, and attenuated hepatic steatosis, while also identifying MAO-A inhibition as an off-target activity. Dimet-Wiley 2024 (aged mice, 8 weeks) showed approximately 40% greater grip strength in NNMT-inhibitor-treated sedentary mice versus controls. No human clinical trial has been published.

AHK-Cu (Copper Tripeptide-3) is a synthetic copper-chelated tripeptide composed of alanine-histidine-lysine, differing from the naturally occurring GHK-Cu by a single amino acid substitution (alanine replaces glycine at position 1). Its entire published evidence base consists of one study: Pyo et al. (2007, Archives of Pharmacal Research), an ex vivo organ culture study showing statistically significant hair follicle elongation (p less than 0.001) and increased dermal papilla cell proliferation at picomolar-to-nanomolar concentrations from 240 human hair follicles across 3 donors. Anti-apoptotic protein markers shifted but apoptosis reduction was not statistically significant. No human clinical trial of AHK-Cu has been published.

Cardiogen (Ala-Glu-Asp-Arg, AEDR) is a synthetic tetrapeptide derived from cardiac tissue protein analysis, developed by Professor Khavinson's group as the heart-targeted member of the Khavinson bioregulator family. Its published evidence base is entirely preclinical: cell culture studies showing 2 to 5 times upregulation of cytoskeletal proteins and reduced apoptosis markers in fibroblasts, a coronary ligation mouse model reporting threefold mortality reduction, and a rat sarcoma model showing dose-dependent tumor inhibition via vascular disruption. No completed human clinical trials have been published. Unlike Vesugen, which has Russian observational data in cardiovascular patients, Cardiogen has no human clinical data of any kind in indexed literature.

Cortagen (Ala-Glu-Asp-Pro) is a synthetic tetrapeptide derived from bovine brain cortex extract (Cortexin), developed by Vladimir Khavinson's group in St. Petersburg. It is proposed to remodel chromatin and reactivate silenced genes in neural and cardiac tissue. Rat studies show 27% faster nerve fiber growth and 40% higher conduction velocity after sciatic nerve transection. No published, peer-reviewed human clinical trial exists. A 2004 background-section claim of human therapeutic use has no primary citation and cannot be treated as clinical evidence. This is a Tier 4 compound.

Dihexa is a synthetic angiotensin IV derivative proposed to amplify HGF/c-Met signaling. Its foundational mechanistic paper was formally retracted in April 2025 for research misconduct. Its pharmaceutical successor compound (fosgonimeton) failed all endpoints in a Phase 2/3 Alzheimer's trial (n=312, September 2024). Zero human clinical trials of dihexa itself exist. The c-Met proto-oncogene safety concern is completely uncharacterized.

FOXO4-DRI (also called Proxofim) is a 26-amino-acid cell-penetrating D-retro-inverso peptide designed to disrupt the FOXO4-p53 protein-protein interaction that keeps senescent cells alive. Published in Cell in 2017 by Baar et al. at Erasmus University Medical Center, it represents the first peptide-based senolytic: a compound that selectively induces apoptosis in senescent cells while sparing healthy tissue. In mouse studies, it reversed chemotoxicity from doxorubicin, restored fur density and fitness in fast-aging and naturally aged mice, and improved renal function. The mechanism has been structurally characterized by NMR in a 2025 Nature Communications paper. No human clinical trial has been published. Cleara Biotech, formed to commercialize the original work, has moved beyond FOXO4-DRI itself to develop optimized derivatives CL04177 and CL04183 now in pre-IND/IMPD studies. Widespread human self-experimentation with commercially available FOXO4-DRI is occurring without safety or efficacy data.

GH Fragment 176-191 is the unmodified 16-amino-acid C-terminal fragment of human growth hormone (residues 176-191), identified as responsible for growth hormone's lipolytic activity. It differs from AOD-9604 (profiled at order 33) by a single amino acid at the N-terminus: phenylalanine versus tyrosine. Critically, GH Fragment 176-191 has no published human clinical trial. Every human clinical finding in this peptide class belongs to AOD-9604 specifically. Animal evidence shows significant fat oxidation and weight loss in obese mice without GH receptor activation or IGF-1 elevation. WADA explicitly names both AOD-9604 and hGH 176-191 as prohibited growth hormone fragments under S2.

IGF-1 LR3 is an 83-amino-acid synthetic analogue of human IGF-1, engineered with two structural modifications that reduce binding to IGF-binding proteins (IGFBPs) by approximately 1,000-fold and extend half-life from the native IGF-1's 10 to 15 minutes to approximately 20 to 30 hours. It is primarily used as a cell culture additive for maintaining human pluripotent stem cells, organoids, and biopharmaceutical production. Zero human clinical trials have been completed. All anabolic, body composition, and recovery claims originate from animal studies and mechanistic extrapolation from native IGF-1 data. The cancer risk signal from IGF-1 receptor biology is the most significant safety concern and is unsettled. This is the highest-risk compound in this research series from an evidence-to-use-pattern mismatch perspective.

Livagen (Lys-Glu-Asp-Ala, KEDA) is a Khavinson tetrapeptide designed from liver tissue peptide analysis. Its distinctive position in the family comes from two mechanistically specific findings: the 2002 Khavinson/Lezhava indexed study demonstrated chromatin deheterochromatinization in human lymphocytes from elderly donors (activation of ribosomal genes and decondensation of pericentromeric heterochromatin), and the 2003 Kost et al. study from the Mental Health Research Center in Moscow (an external institution) found that Livagen inhibits enkephalin-degrading enzymes in human serum with an IC50 of 20 micromolar, outperforming known peptidase inhibitors puromycin, leupeptin, and D-PAM. Neither study constitutes a clinical trial. No human efficacy data in any disease indication has been published.

PE 22-28 is a synthetic 7-amino acid peptide derived from positions 22 to 28 of the sortilin propeptide (PE). It is the most potent known selective TREK-1 potassium channel antagonist, with an IC50 of 0.12 nM versus 40 to 60 nM for its parent compound spadin, and produces antidepressant-like effects within 4 days in mouse behavioral models versus 21 days for fluoxetine. All evidence is preclinical from a single French research group. No human has received PE 22-28 in a clinical trial.

PEG-MGF (Pegylated Mechano Growth Factor) is a synthetic analog of MGF, the 24-amino-acid E-domain peptide of the IGF-1Ec splice variant naturally released in skeletal muscle in response to mechanical damage. PEGylation extends the half-life from minutes to an estimated 24 to 72 hours. MGF has been WADA-prohibited under S2 since 2005. No human interventional trial of PEG-MGF or exogenous MGF has been published. Animal evidence includes satellite cell activation, cardiac protection post-infarction in sheep (Carpenter 2008: 35% less compromised myocardium), and progenitor cell increases in ALS and DMD mouse models. Observational human data shows blunted endogenous MGF expression in elderly versus young men after resistance exercise (Hameed 2003, n=34). The IGF-1 pathway oncology risk is a meaningful theoretical safety concern.

PNC-27 is a 32-residue chimeric peptide combining a domain from the tumor suppressor protein p53 with a membrane-penetrating sequence. It kills a wide range of cancer cell types in vitro and in mouse models by binding to HDM-2 (human double minute-2) protein expressed on cancer cell membranes, forming transmembrane pores that lyse the cell. Normal cells, which express little or no membrane-bound HDM-2, are largely spared. Despite 20-plus years of laboratory research, no human clinical trial has been conducted, and a separate commercial operation selling PNC-27 as a cancer cure was publicly warned against by the FDA in 2017 for bacterial contamination.

SLU-PP-332 is a synthetic small molecule that activates all three estrogen-related receptor subtypes (ERRalpha, ERRbeta, ERRgamma), triggering a gene expression program that closely resembles the response to acute aerobic exercise. In multiple mouse studies it has increased endurance, reduced fat mass, improved insulin sensitivity, and shown protection against heart failure and age-related kidney dysfunction. No human trials have been conducted.

Thymosin beta-4 sulfoxide (Tβ4-SO) is a naturally occurring oxidation derivative of the parent peptide thymosin beta-4, formed when the methionine-6 residue of Tβ4 is oxidized by hydrogen peroxide (H2O2) at sites of inflammation. It is a distinct compound from its parent: oxidation attenuates Tβ4's intracellular G-actin sequestering function but substantially enhances its extracellular anti-inflammatory and immune-resolution signaling. TB4-SO is not the same compound as TB-500 (the actin-binding fragment Ac-LKKTETQ used in the peptide community) nor the same as Tβ4 itself. Evidence is limited to two key publications: the 1999 Young et al. Nature Medicine paper establishing glucocorticoid-induced monocyte production and in vitro/in vivo anti-inflammatory effects, and the 2013 Evans et al. Nature Communications paper demonstrating cardiac wound healing promotion in zebrafish, mouse, and human cell culture. No human clinical trials have been conducted.

Vilon (Lys-Glu) is the smallest member of the Khavinson bioregulator family: a synthetic dipeptide derived from thymic tissue designed to reactivate age-silenced gene expression. Its in vitro chromatin remodeling data in human aged lymphocytes are mechanistically compelling, and the CBA mouse longevity findings span two decades. The HER-2/neu pro-tumorigenic finding in the same research program is a safety signal most vendor content omits entirely. No human clinical trials have been published after four decades of animal research.