Research library
The research library
Every primary source behind a claim on this site, tier-graded for provenance and tagged for the strength of the evidence it carries.
- Sources indexed
- 221
- Peptides covered
- 44
- Tier 1 share
- 100%
- Matching filter
- 42
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Reset allT1·Peer-primary literature
Randomized trials, peer-reviewed primary studies, and meta-analyses — the load-bearing layer of the corpus.
42 sources
- 2026Mechanisticstrong
Cav3.1 is a neuronal leucine sensor that mediates satiety and weight loss in response to dietary protein
Tsang AH, Heeley N, Alcaino C, +3 · Cell Metabolism
Cambridge Institute of Metabolic Science group identifies Cav3.1 — a T-type voltage-gated calcium channel — as the hypothalamic POMC-neuron leucine sensor that mediates protein-induced satiety, and shows pharmacological Cav3.1 activation in the mediobasal hypothalamus drives weight loss in obese mice and potentiates liraglutide's anorectic response.
- 2026Mechanisticmoderate
GIPR:GCGR co-agonism restores normal weight in obese rodents
Perez-Tilve D, Zhang F, Zhang Y, +6 · Molecular Metabolism
BWB3054, a dual GIPR:GCGR co-agonist designed to attenuate GLP-1R signalling >100-fold, normalised body weight in diet-induced obese mice and rats and matched retatrutide's weight effect — including in GLP-1R-knockout mice — suggesting the GIP and glucagon arms of the triple-agonist can deliver the bulk of the obesity effect without GLP-1R-driven gastrointestinal liability.
- 2026Mechanisticsuggestiven=120
Combined antiretroviral therapy with low- or normal-protein, high-calorie diets appears to induce significant deleterious electrocardiographic changes in a rodent model
Chege BM, Mwangi PW, Githinji CG, +1 · Brazilian Journal of Medical and Biological Research
In 120 Sprague-Dawley rats fed calorie-dense diets and dosed with dolutegravir-based or classical combination antiretroviral regimens for 24 weeks, addition of tesamorelin prevented the ECG conduction abnormalities and myocardial fibrosis seen with dolutegravir or classical cART alone — implicating growth-hormone-axis dysfunction in cART-associated cardiotoxicity.
- 2026Mechanisticsuggestive
Anti-inflammatory and anabolic effects of liraglutide on 3D inflammatory osteoarthritic spheroid and scaffold models of human chondrocytes
Ciftci E, Eberlein SC, Grad S, +3 · Osteoarthritis and Cartilage
In 3D human-chondrocyte spheroid and scaffold cultures stimulated with IL-1β, liraglutide reduced IL-8 release roughly four-fold (877.8 vs 3127.0 ng), elevated ACAN and PRG4 anabolic markers, and preserved extracellular-matrix composition under cyclic mechanical loading — the first systematic in-vitro mechanistic case for a direct GLP-1RA effect on osteoarthritic cartilage independent of weight loss.
- 2026Mechanisticsuggestive
Glycyl-L-histidyl-L-lysine-Cu2+ (GHK-Cu) Attenuates CuSO4 or LPS induced-inflammation in Zebrafish larvae model
Hu J, Zhang C, Wang F · European Journal of Pharmacology
In a zebrafish larvae inflammation model, GHK-Cu suppressed neutrophil and macrophage migration, downregulated TNF-α, IL-1β, and IL-6, upregulated IL-10, and attenuated JAK1 signalling — extending the cosmetic-skin GHK-Cu literature into a whole-organism inflammation readout.
- 2023Mechanisticsuggestiven=30
Thymosin alpha 1 restores the immune homeostasis in lymphocytes during Post-Acute sequelae of SARS-CoV-2 infection
Minutolo A, Petrone V, Fanelli M, +16 · International Immunopharmacology
An ex-vivo study from the Garaci–Matteucci group examining lymphocyte populations in 10 PASC patients, 15 acute-COVID-19 controls, and 5 healthy donors — the only PASC-specific thymosin α-1 paper in the indexed literature, documenting persistent immune dysregulation and partial ex-vivo rescue with greatest effect in patients who had required respiratory support during the acute phase.
- 2021Mechanisticmoderaten=224
Immune-Based Prediction of COVID-19 Severity and Chronicity Decoded Using Machine Learning
Patterson BK, Guevara-Coto J, Yogendra R, +7 · Frontiers in Immunology
A 224-individual immune-profiling study that documented PASC-distinctive elevations in CCL5/RANTES, IL-2, IL-4, CCL3, IL-6, IL-10, IFN-γ, and VEGF alongside expanded CD14+/CD16+/CCR5+ monocyte subsets — the most-cited immune-signature characterisation in the early PASC literature, and structurally separate from the same group's subsequent treatment claims.
- 2021Mechanisticstrong
MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis
Reynolds JC, Lai RW, Woodhead JST, +9 · Nature Communications
Acute exercise raised skeletal-muscle MOTS-c expression nearly 12-fold and circulating MOTS-c by approximately 50% in human volunteers; exogenous MOTS-c administered to mice approximately doubled treadmill running capacity at young, middle-aged, and old time points — the strongest single-paper integration of MOTS-c human physiology and mouse pharmacology to date.
- 2021Mechanisticstrong
Molecular Engineering of Insulin Icodec, the First Acylated Insulin Analog for Once-Weekly Administration in Humans
Kjeldsen TB, Hubálek F, Hjørringgaard CU, +15 · Journal of Medicinal Chemistry
Three insulin substitutions (A14E, B16H, B25H) plus a C20 fatty-diacid acylation at LysB29 — the molecular-engineering combination that produced a ~196-hour terminal half-life and made once-weekly basal insulin a clinical reality.
- 2021Mechanisticmoderaten=49
Persistent clotting protein pathology in Long COVID/Post-Acute Sequelae of COVID-19 (PASC) is accompanied by increased levels of antiplasmin
Pretorius E, Vlok M, Venter C, +4 · Cardiovascular Diabetology
The foundational microclot-in-PASC observation paper — fluorescent staining and proteomics on plasma from 11 PASC patients identified amyloid fibrin deposits resistant to trypsin-mediated fibrinolysis, with α2-antiplasmin elevated approximately eightfold within the resistant pellet versus healthy controls.
- 2021Mechanisticstrong
Development of Cagrilintide, a Long-Acting Amylin Analogue
Kruse T, Hansen JL, Dahl K, +12 · Journal of Medicinal Chemistry
The molecular design paper for cagrilintide — a stabilised, lipidated long-acting analogue of pramlintide engineered around the same C20-fatty-diacid + albumin-binding architecture that produced once-weekly semaglutide, here transplanted onto an amylin backbone.
- 2020Mechanisticstrong
Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist
Willard FS, Douros JD, Gabe MBN, +15 · JCI Insight
Tirzepatide is not a balanced dual GIP / GLP-1 agonist — it engages the GIP receptor with native-ligand potency and the GLP-1 receptor with approximately 5-fold weaker affinity, and at the GLP-1 receptor it is biased toward cAMP signaling over β-arrestin recruitment.
- 2018Mechanisticmoderate
Selective and membrane-permeable small molecule inhibitors of nicotinamide N-methyltransferase reverse high fat diet-induced obesity in mice
Neelakantan H, Vance V, Wetzel MD, +5 · Biochemical Pharmacology
Eleven days of subcutaneous 5-Amino-1MQ at 20 mg/kg three times daily produced approximately 5% body weight loss and a roughly 35% reduction in epididymal white adipose tissue mass in diet-induced-obese mice — the pharmacological replication of the Kraus 2014 antisense-knockdown phenotype that anchors every subsequent NNMT-inhibitor claim.
- 2018Mechanisticstrong
LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept
Coskun T, Sloop KW, Loghin C, +13 · Molecular Metabolism
The discovery paper for LY3298176 — later named tirzepatide — established the molecule as a single 39-residue, fatty-acid-conjugated peptide engineered to engage both the GIP and GLP-1 receptors with once-weekly pharmacokinetics, framing it explicitly as a unimolecular dual agonist rather than a co-administered combination.
- 2017Mechanisticmoderate
GABA, Selank, and Olanzapine Affect the Expression of Genes Involved in GABAergic Neurotransmission in IMR-32 Cells
Filatova E, Kasian A, Kolomin T, +8 · Frontiers in Pharmacology
Selank alone produced no change in GABAergic gene expression in IMR-32 cells; the effect appeared only in combination with GABA or olanzapine — the cleanest Western-indexed mechanism paper showing Selank as a co-modulator rather than a primary releaser.
- 2015Mechanisticstrong
The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance
Lee C, Zeng J, Drew BG, +8 · Cell Metabolism
MOTS-c — the first mitochondrial-encoded peptide characterized as a circulating signaling molecule — prevented age- and diet-induced insulin resistance in mice through skeletal-muscle AMPK activation.
- 2015Mechanisticsuggestiven=32
Effect of intra-articular injection of AOD9604 with or without hyaluronic acid in rabbit osteoarthritis model
Kwon DR, Park GY · Annals of Clinical and Laboratory Science
In 32 rabbits with collagenase-induced knee osteoarthritis, combined weekly intra-articular AOD-9604 plus hyaluronic acid produced better histological cartilage and lameness scores than either agent alone — the only published animal-model evidence for AOD-9604's post-obesity-program orthopaedic indication.
- 2015Mechanisticstrong
Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide
Lau J, Bloch P, Schäffer L, +5 · Journal of Medicinal Chemistry
The molecular design paper for semaglutide — the C18 fatty diacid plus the Aib(8) substitution, paired together to produce week-long albumin binding and full DPP-4 resistance, were the design moves that opened once-weekly GLP-1 dosing as a clinical category.
- 2014Mechanisticstrong
Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity
Kraus D, Yang Q, Kong D, +16 · Nature
Antisense knockdown of nicotinamide N-methyltransferase in white adipose tissue and liver of diet-induced-obese mice protected against weight gain, improved insulin sensitivity, and elevated tissue SAM and NAD+ levels — without changes in food intake. The mechanistic anchor for every subsequent 5-Amino-1MQ paper.
- 2013Mechanisticstrong
The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin
Birk AV, Liu S, Soong Y, +6 · Journal of the American Society of Nephrology
Birk and Szeto demonstrated that SS-31 binds cardiolipin selectively on the inner mitochondrial membrane, inhibits cytochrome c peroxidase activity, preserves cristae structure during ischemia, and accelerates ATP recovery after renal reperfusion — the foundational mechanism paper for every subsequent SS-31 indication.
- 2013Mechanisticmoderate
Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents
McCoy AT, Benoist CC, Wright JW, +6 · Journal of Pharmacology and Experimental Therapeutics
Dihexa restored cognitive performance in scopolamine-impaired and aged rats, distributed effectively to brain after oral administration, and produced marked synaptogenic activity in hippocampal cultures — the foundational paper for everything that followed.
- 2010Mechanisticmoderate
Cardioprotection by a nonerythropoietic, tissue-protective peptide mimicking the 3D structure of erythropoietin
Ueba H, Brines M, Yamin M, +5 · PNAS
The 11-amino-acid helix B surface peptide that became ARA-290 inhibits TNF-α-induced cardiomyocyte apoptosis by approximately 80% and reduces in-vivo cardiac apoptosis by approximately 70% in a hamster dilated-cardiomyopathy model — extending the IRR mechanism into a cardiac-protection indication that did not progress to clinical development.
- 2008Mechanisticmoderate
Pentadecapeptide BPC 157, in clinical trials as a therapy for inflammatory bowel disease (PL14736), is effective in the healing of colocutaneous fistulas in rats: role of the nitric oxide-system
Klicek R, Sever M, Radic B, +17 · Journal of Pharmacological Sciences
BPC-157 accelerated closure of colon-to-skin fistulas in rats whether given by injection or orally; corticosteroids — the conventional comparator — worsened healing.
- 2008Mechanisticmoderate
PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation
Dalmasso G, Charrier-Hisamuddin L, Nguyen HTT, +3 · Gastroenterology
KPV enters epithelial and immune cells through PepT1, suppresses NF-κB at nanomolar concentrations, and reduces colitis severity in two independent mouse models — the foundational paper for the entire current case for KPV in inflammatory bowel disease.
- 2008Mechanisticstrong
Nonerythropoietic, tissue-protective peptides derived from the tertiary structure of erythropoietin
Brines M, Patel NSA, Villa P, +13 · PNAS
An eleven-amino-acid peptide reproducing the aqueous face of helix B of human erythropoietin retains the tissue-protective activity of EPO across stroke, retinal, renal, and peripheral-nerve injury models while remaining inactive at the homodimeric EPO receptor — the foundational design paper for ARA-290 / cibinetide.
- 2008Mechanisticmoderate
Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease
Kannengiesser K, Maaser C, Heidemann J, +7 · Inflammatory Bowel Diseases
KPV given orally rescued every animal in the MC1Re/e DSS-colitis arm from death — demonstrating that the tripeptide's anti-inflammatory activity does not require a functional melanocortin-1 receptor and runs in parallel to the Dalmasso PepT1-transport mechanism.
- 2007Mechanisticmoderate
Non-clinical pharmacology and safety evaluation of TH9507, a human growth hormone-releasing factor analogue
Ferdinandi ES, Brazeau P, High K, +3 · Basic and Clinical Pharmacology & Toxicology
The preclinical design and characterization paper for tesamorelin — TH9507's hexenoyl modification of native GHRH conferred DPP-IV resistance and a 21–45 minute half-life in dogs, the engineering moves that enabled the clinical-trial program.
- 2007Mechanisticmoderate
Thymosin beta4 induces adult epicardial progenitor mobilization and neovascularization
Smart N, Risebro CA, Melville AAD, +4 · Nature
Thymosin β4 stimulated outgrowth from quiescent adult epicardial explants, restoring pluripotency and triggering differentiation into fibroblasts, smooth muscle cells, and endothelial cells — the second foundational Nature paper that drove the cardiac-repair clinical-development arc.
- 2006Mechanisticmoderaten=8
Pulsatile Secretion of Growth Hormone (GH) Persists during Continuous Stimulation by CJC-1295, a Long-Acting GH-Releasing Hormone Analog
Ionescu M, Frohman LA · Journal of Clinical Endocrinology & Metabolism
After a single subcutaneous dose, CJC-1295 elevated trough GH by 7.5-fold and IGF-I by 45% while leaving the frequency and amplitude of GH pulses unchanged — a continuous GHRH signal that does not flatten physiological pulsatility.
- 2006Mechanisticmoderate
Achilles detachment in rat and stable gastric pentadecapeptide BPC 157: promoted tendon-to-bone healing and opposed corticosteroid aggravation
Krivic A, Anic T, Seiwerth S, +2 · Journal of Orthopaedic Research
Tendon-to-bone — a tissue interface that does not heal spontaneously after sharp transection in rats — was functionally and biomechanically restored by intraperitoneal BPC-157, including in animals concurrently treated with corticosteroids that worsened healing alone.
- 2005Mechanisticmoderate
Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents
Eremin KO, Kudrin VS, Saransaari P, +4 · Neurochemical Research
Semax did not move dopamine on its own, but pretreatment dramatically enhanced amphetamine-induced dopamine release — a neuromodulatory amplifier rather than a primary releaser.
- 2004Mechanisticmoderate
Thymosin beta4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair
Bock-Marquette I, Saxena A, White MD, +2 · Nature
Thymosin β4 promoted myocyte migration and survival through an integrin-linked-kinase / Akt pathway and improved cardiac function in mice after coronary artery ligation — the mechanistic foundation for everything that followed in the cardiac-repair literature.
- 2003Mechanisticmoderate
Epithalon peptide induces telomerase activity and telomere elongation in human somatic cells
Khavinson VKh, Bondarev IE, Butyugov AA · Bulletin of Experimental Biology and Medicine
In telomerase-negative human fetal fibroblasts, Epithalon induced expression of the telomerase catalytic subunit, enzymatic activity, and telomere elongation — the foundational mechanistic claim that anchors the entire modern Epitalon literature.
- 2002Mechanisticstrong
CD36 mediates the cardiovascular action of growth hormone-releasing peptides in the heart
Bodart V, Febbraio M, Demers A, +8 · Circulation Research
A radioactive photoactivatable hexarelin derivative cross-linked to an 84-kDa cardiac membrane protein identified by sequencing as CD36 — and the hexarelin coronary-perfusion-pressure effect was abolished in CD36-null mice and in CD36-deficient spontaneously hypertensive rats. The molecular identification of hexarelin's cardiac receptor.
- 2001Mechanisticmoderate
The Effects of Human GH and Its Lipolytic Fragment (AOD9604) on Lipid Metabolism Following Chronic Treatment in Obese Mice and β3-AR Knock-Out Mice
Heffernan M, Summers RJ, Thorburn A, +4 · Endocrinology
Both hGH and AOD-9604 upregulated β3-adrenergic-receptor expression and produced weight loss in obese wild-type mice, but neither compound sustained those effects in β3-AR knockout animals — the experiment that localised AOD-9604's lipolytic mechanism to the β3 channel.
- 2000Mechanisticmoderate
Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone
Ng FM, Sun J, Sharma L, +3 · Hormone Research
Nineteen days of oral 500 µg/kg/day AOD-9604 in obese Zucker rats reduced body-weight gain by more than half versus control (15.8 vs. 35.6 g), increased ex vivo adipose lipolytic activity, and produced no detectable insulin-sensitivity decrement under euglycemic clamp — the foundational preclinical paper for the molecule.
- 1999Mechanisticstrongn=40
Pharmacokinetic-Pharmacodynamic Modeling of Ipamorelin, a Growth Hormone Releasing Peptide, in Human Volunteers
Gobburu JV, Agersø H, Jusko WJ, +1 · Pharmaceutical Research
Ipamorelin's terminal half-life is roughly two hours and clearance is 0.078 L/h/kg — short enough that the GH pulse it produces is over within six hours, the pharmacological signature behind its 'physiological pulse' reputation.
- 1998Mechanisticstrong
Ipamorelin, the first selective growth hormone secretagogue
Raun K, Hansen BS, Johansen NL, +4 · European Journal of Endocrinology
At doses more than 200-fold above the ED50 for GH release, Ipamorelin produced no significant elevation of ACTH, cortisol, prolactin, FSH, LH, or TSH — the selectivity that distinguished it from every prior GHRP.
- 1992Mechanisticstrong
The cloning of a family of genes that encode the melanocortin receptors
Mountjoy KG, Robbins LS, Mortrud MT, +1 · Science
The original cloning paper for the melanocortin receptor family — identification of the murine and human MSH receptor and the human ACTH receptor as G-protein-coupled receptors, deposited in GenBank as X65633, X65634, and X65635. The molecular foundation of every melanocortin-targeted peptide on this site.
- 1979Mechanisticstrong
Expression in Escherichia coli of chemically synthesized genes for human insulin
Goeddel DV, Kleid DG, Bolivar F, +7 · Proceedings of the National Academy of Sciences of the United States of America
The paper that turned synthetic biology into pharmaceutical manufacturing — separate E. coli expression of the A and B chains as β-galactosidase fusions, chemical cleavage, in vitro chain reassembly, and a biologically active human insulin three years before Humulin reached the market.
- 1978Mechanisticmoderate
The delta EEG (sleep)-inducing peptide (DSIP). XI. Amino-acid analysis, sequence, synthesis and activity of the nonapeptide
Schoenenberger GA, Maier PF, Tobler HJ, +2 · Pflügers Archiv
Synthetic DSIP, given to recipient rabbits, reproduced the original blood-fraction's delta- and spindle-EEG-enhancing activity — a 35% delta-power increase in neocortex and limbic cortex versus controls.
- 1963Mechanisticstrong
Solid Phase Peptide Synthesis. I. The Synthesis of a Tetrapeptide
Merrifield RB · Journal of the American Chemical Society
The 1963 JACS paper that introduced solid-phase peptide synthesis — anchoring the C-terminal amino acid to an insoluble polymer support and extending the chain through repeated coupling cycles. The methodology earned Merrifield the 1984 Nobel Prize in Chemistry and remains the workhorse of synthetic-peptide manufacturing six decades later.