Daily updates on peptide research, clinical trials, regulatory changes, and site additions.
A five-target obesity peptide conjugate, Lilly's black-market crackdown on retatrutide, and fresh Phase 2 data lead today's peptide digest.
Read full briefingIcotrokinra is now on PeptideWiki. FDA-approved in March 2026 (brand name Icotyde) for moderate-to-severe plaque psoriasis, it's the first oral macrocyclic peptide to antagonize the IL-23 receptor directly — a pill where the class previously required injectable antibodies.
Palopegteriparatide (Yorvipath, TransCon PTH) is now on PeptideWiki. Its PEGylated carrier releases free PTH(1-34) gradually rather than in an injection-driven spike, approximating continuous hormone tone — FDA-approved 2024 for hypoparathyroidism.
Pegulicianine (Lumisight) is now on PeptideWiki. This peptide-dye conjugate stays optically dark until tumor-associated proteases cleave its linker, lighting up residual breast cancer at surgical margins in real time — FDA-approved 2024.
Orforglipron (Foundayo) is now on PeptideWiki. FDA-approved April 2026 for weight management, it's a non-peptide small molecule GLP-1 receptor agonist — included for direct comparison against the peptide GLP-1 drugs it competes with.
Three investigational obesity-pipeline peptides join PeptideWiki: VK2735 (Viking Therapeutics, dual GLP-1/GIP), Amycretin (Novo Nordisk, unimolecular GLP-1/amylin), and Pemvidutide (Altimmune, dual GLP-1/glucagon, also in Phase 3 for MASH). None are yet FDA-approved.
Two dimeric dipeptide compounds from the Zakusov Institute (Russia) join PeptideWiki: GK-2, a selective TrkA-activating NGF mimetic, and GSB-106, a TrkB-activating BDNF mimetic with antidepressant-like effects in rodent models. Both are preclinical-only — no human trial data exists for either.
Regulatory heat, GLP-1 milestones, and four studies worth watching — today's roundup.
PeptideWiki adds Thymalin (Khavinson's thymic polypeptide complex with 6-year human longevity data), VIP (Vasoactive Intestinal Peptide — the cornerstone of the Shoemaker CIRS protocol and a potent anti-inflammatory neuropeptide), and Hexarelin (the most potent GHRP with unique cardioprotective CD36 effects). Full mechanism breakdowns, dosage protocols, cycle guides, and citations included.
PeptideWiki has added four new research compounds: GHRP-6 (the classic GH secretagogue and GHSR1a agonist), FOXO4-DRI (the groundbreaking senolytic peptide from de Keizer's 2017 Cell paper), Adropin (the ENHO-encoded hepatokine linking energy homeostasis to cardiovascular health), and LA-31 (a lactoferrin-derived antimicrobial and autophagy-activating peptide). Each entry includes full mechanism breakdowns, dosage protocols, cycle guides, and research citations.
PeptideWiki has added 10 new research peptides spanning muscle biology (Follistatin-344, ACE-031), longevity (MOTS-c, NAD+), hormonal health (Bremelanotide/Vyleesi, Gonadorelin), nootropics (Cerebrolysin, Pinealon), healing (TB4-Frag), and oncology research (PNC-27). Each entry features full mechanism breakdowns, dosage protocols, and research applications.
PNC-27 is now on PeptideWiki. This 32-amino acid chimeric peptide fuses a p53 transactivation domain sequence with a membrane-penetrating leader sequence, creating a cancer-selective cytotoxic agent. Unlike conventional p53 activators, PNC-27 bypasses the nuclear pathway entirely — it physically inserts into cancer cell membranes (where MDM2 is aberrantly expressed), forming pores that trigger selective necrosis. Normal cells, which lack membrane MDM2, are spared. Entry covers MDM2 membrane hypothesis, selective pore formation mechanism, and pancreatic/breast cancer preclinical data.
TB4-Frag (Ac-LKKTETQ-OH) is now on PeptideWiki. The 7-amino acid N-terminal fragment of Thymosin Beta-4, TB4-Frag retains full G-actin sequestration activity while offering dramatically improved metabolic stability over the parent 43-AA peptide. It accelerates wound closure via actin cytoskeleton remodelling, promotes corneal and dermal regeneration, and modulates anti-inflammatory signalling through ILK/PI3K pathways. Entry covers the LKKTET pharmacophore, actin dynamics mechanism, wound healing data, and comparison with full TB-500.
Pinealon (Glu-Asp-Arg / EDR) is now on PeptideWiki. Developed by the Khavinson group at the St. Petersburg Institute of Bioregulation, this synthetic tripeptide modelled on a pineal gland-derived peptide penetrates the blood-brain barrier and acts as an epigenetic regulator — binding directly to gene promoter regions to restore expression of antioxidant enzymes (catalase, SOD) and neuroprotective proteins. Preclinical data shows protection against ischemia-induced neuronal apoptosis and partial reversal of age-related cognitive decline. Entry covers epigenetic PCNA-binding mechanism, BBB penetration, and comparisons with Epithalon and Semax.
Cerebrolysin is now on PeptideWiki. A standardised porcine brain-derived hydrolysate containing BDNF-like, NGF-like, and CNTF-like peptide fragments, Cerebrolysin is licensed for acute ischemic stroke in 50+ countries and has completed multiple Phase 3 randomised controlled trials. The CARS (Cerebrolysin And Recovery after Stroke) trial demonstrated significant improvement in NIHSS and mRS scores when added to standard care. Entry covers neurotrophic factor mimicry, BDNF/TrkB signalling, anti-apoptotic mechanisms, and the clinical trial landscape for stroke, TBI, and Alzheimer's disease.
Gonadorelin is now on PeptideWiki. The endogenous 10-amino acid gonadotropin-releasing hormone (GnRH), Gonadorelin is the native signal used by the hypothalamus to drive pituitary LH and FSH release, which in turn stimulates testicular testosterone production. Unlike synthetic GnRH analogues (leuprolide, buserelin), pulsatile gonadorelin preserves normal HPG axis cycling — making it the preferred TRT co-prescription to maintain testicular size and fertility during testosterone therapy. Entry covers pulsatile vs. continuous dosing pharmacodynamics, HPG axis suppression risk, and fertility preservation protocols.
Bremelanotide (PT-141 / Vyleesi) is now on PeptideWiki. FDA-approved in 2019 for hypoactive sexual desire disorder (HSDD) in premenopausal women, bremelanotide is the first CNS-targeted sexual dysfunction treatment — acting via MC3R/MC4R in the hypothalamus to increase sexual motivation and arousal rather than simply improving genital blood flow like PDE5 inhibitors. The drug was serendipitously discovered from Melanotan II during sunless tanning research. Entry covers melanocortin receptor pharmacology, CNS mechanism, RECONNECT trial data, and the clinical distinction from PDE5 inhibitors.
MOTS-c is now on PeptideWiki. Discovered in 2015, MOTS-c is a 16-amino acid mitochondria-derived peptide (MDP) encoded within the mitochondrial 12S rRNA region — making it the only known hormone encoded entirely by mitochondrial DNA. It activates AMPK in skeletal muscle and metabolic tissues, mimicking the gene expression changes of aerobic exercise. Its performance-enhancing potential was deemed significant enough for WADA to add it to the prohibited list in 2024. Entry covers mitochondrial genome encoding, AMPK pathway, insulin sensitisation, and the exercise-mimetic phenotype data.
NAD+ (Nicotinamide Adenine Dinucleotide) now has a full entry on PeptideWiki. The master metabolic coenzyme declines ~50% between ages 20 and 60, and restoring it via precursors NMN and NR has become a central strategy in longevity research. NAD+ activates sirtuins (SIRT1–7) for epigenetic deacetylation, fuels PARP-mediated DNA repair, and drives mitochondrial complex I electron transport. Human trials confirm NMN raises blood NAD+ in a dose-dependent manner (Igarashi et al., npj Aging 2022) and improves skeletal muscle insulin signalling (Yoshino et al., Science 2021). Entry covers sirtuin biology, PARP competition, CD38 age-related degradation, and NMN vs NR precursor comparisons.
ACE-031 (Ramatercept) is now on PeptideWiki. A fusion protein combining the ligand-binding domain of activin receptor IIA (ActRIIA) with an IgG1-Fc domain, ACE-031 acts as a soluble decoy receptor that simultaneously blocks myostatin, activin A/B, GDF-11, and BMP-9/10 — outperforming selective myostatin antibodies by targeting the entire ligand family. In mdx (Duchenne) mice, ACE-031 produced near-doubling of muscle mass. Phase 2 trials in Duchenne muscular dystrophy were halted in 2013 due to telangiectasia and epistaxis adverse events at high doses. Entry covers the ActRIIA ligand family, Smad2/3 suppression mechanism, Phase 2 DMD trial data, and the off-target vascular biology that drove trial termination.
Follistatin-344 (FST-344) is now on PeptideWiki. The predominant follistatin isoform in skeletal muscle, FST-344 is a 344-amino acid glycoprotein that sequesters myostatin (GDF-8) and activin A with sub-nanomolar affinity, physically preventing their binding to ActRIIA/B receptors. Transgenic mice overexpressing FST-344 develop 200–300% greater muscle mass than controls with no cardiac hypertrophy — the most dramatic anabolic phenotype achieved by a single gene in mammals. AAV-delivered FST-344 gene therapy is currently in Phase 1/2 trials for Duchenne muscular dystrophy and spinal muscular atrophy. Entry covers follistatin isoform biology, Smad2/3 pathway disinhibition, satellite cell activation, and the gene therapy clinical landscape.
PeptideWiki has expanded its database with six highly-requested research peptides. The additions span growth hormone secretagogues (MK-677/Ibutamoren), innate immunity (LL-37/Cathelicidin), gut anti-inflammatories (KPV), mitochondrial medicine (SS-31/Elamipretide, Humanin), and cognitive enhancement (Dihexa). Each entry includes full mechanism breakdowns, dosage protocols, research applications, and key citations.
MK-677 is now on PeptideWiki. As the only oral GH secretagogue with Phase 2/3 human trial data, it offers a distinct profile from injectable GH peptides: 24-hour half-life, 40–90% IGF-1 elevation, documented lean mass gains in elderly adults, and improved slow-wave sleep. Entry covers GHSR-1a mechanism, sleep architecture effects, sarcopenia trial data, and adverse effect monitoring.
LL-37 is now on PeptideWiki. The sole human cathelicidin, LL-37 is a multifunctional 37-amino acid peptide that kills bacteria via membrane disruption, disrupts biofilms, modulates innate immune responses, and accelerates wound healing via EGFR transactivation. Its deficiency underlies atopic dermatitis, chronic rhinosinusitis, and recurrent infections. Entry covers antimicrobial spectrum, immunomodulation via FPRL1/FPR2, and wound healing mechanisms.
KPV (Lys-Pro-Val), the anti-inflammatory C-terminal tripeptide of α-MSH, is now on PeptideWiki. At 328 Da, its small size enables oral bioavailability and deep mucosal penetration — an advantage over full α-MSH for gastrointestinal applications. Nanoparticle-formulated KPV achieved colitis remission comparable to mesalamine in multiple preclinical IBD models. Entry covers NF-κB inhibition, epithelial barrier repair, and gut-targeted delivery systems.
SS-31 (Elamipretide/MTP-131) is now on PeptideWiki. The SPARCLE Phase 3 trial demonstrated significant improvements in 6-minute walk test and quality of life in heart failure — making SS-31 the first mitochondria-targeted therapy to reach positive Phase 3 outcomes. Its mechanism centers on cardiolipin binding at the inner mitochondrial membrane, preserving cristae architecture and ATP synthase efficiency. Entry covers cardiolipin biology, SPARCLE/TAZPOWER trial data, and Barth syndrome application.
Humanin is now on PeptideWiki. The founding mitochondria-derived peptide (MDP), Humanin is encoded by the mitochondrial 16S rRNA region and signals systemically as a longevity factor. Centenarians maintain significantly higher circulating humanin levels than age-matched controls. It suppresses neuronal apoptosis (Bax inhibition), improves insulin sensitivity via gp130/WSX-1 receptors, and protects the heart from ischemia-reperfusion injury. Entry covers MDP biology, centenarian data, and HNG analogue pharmacology.
Dihexa is now on PeptideWiki. This synthetic angiotensin IV analogue (Washington State University) potentiates HGF/MET receptor signaling in the brain, inducing synaptogenesis and dendritic spine growth. Preclinical data reported ~10 million-fold greater potency vs. BDNF for synaptogenesis in hippocampal neurons. In aged cognitively-impaired rats, 5 days of treatment restored Morris Water Maze performance to young-animal levels. Blood-brain barrier penetrant via oral or transdermal routes.
NAD+ (Nicotinamide Adenine Dinucleotide) has been added to PeptideWiki's Longevity category. The entry covers sirtuin activation, PARP-mediated DNA repair, mitochondrial function, and the age-related ~50% NAD+ decline. Includes 5 key citations from Cell Metabolism, Science, and npj Aging.
A 2025 PMC publication (Kossoy et al.) provides independent Western validation of Epithalon's telomere-lengthening mechanism, confirming TERT upregulation in human cell lines. This represents important replication of the Khavinson group's 30+ year dataset outside of Russian research institutions.
MOTS-c was added to the World Anti-Doping Agency's prohibited substances list in 2024, classified as a prohibited peptide hormone. This reflects the sports science community's assessment of its performance-enhancing potential via AMPK activation and exercise mimicry — a significant milestone for the young (2015) research peptide.
Igarashi et al. (2022, npj Aging) demonstrated that chronic NMN supplementation significantly elevates blood NAD+ concentrations in healthy older men in a dose-dependent fashion. This human data strengthens the rationale for NMN as an NAD+ precursor for age-related NAD+ decline.
Yoshino et al. (2021, Science) showed NMN supplementation improved skeletal muscle insulin signalling and NAD+ metabolism in premenopausal women with prediabetes. Published in Science, this is one of the highest-impact human NAD+ trials to date and the first to show tissue-level metabolic benefits.