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
- 89%
- Matching filter
- 19
F·Filter
Reset allT1·Peer-primary literature
Randomized trials, peer-reviewed primary studies, and meta-analyses — the load-bearing layer of the corpus.
17 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.
- 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.
- 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
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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
T2·Peer-secondary literature
Peer-reviewed reviews and cohort/observational work — context, not bedrock.
2 sources
- 2005Mechanisticstrong
Human Growth Hormone-Releasing Factor (hGRF)1-29-Albumin Bioconjugates Activate the GRF Receptor on the Anterior Pituitary in Rats: Identification of CJC-1295 as a Long-Lasting GRF Analog
Jetté L, Léger R, Thibaudeau K, +3 · Endocrinology
CJC-1295 was identified as the lead compound from a panel of three hGRF(1-29)-albumin bioconjugates — present in rat plasma beyond 72 hours and producing a fourfold increase in GH AUC versus unmodified hGRF(1-29). This is the molecule's origin story.
- 2004Mechanisticstrong
Selective facilitation of sexual solicitation in the female rat by a melanocortin receptor agonist
Pfaus JG, Shadiack A, Van Soest T, +2 · Proceedings of the National Academy of Sciences
PT-141 selectively increased appetitive sexual behaviors — solicitations and hops-and-darts — in ovariectomized female rats without affecting lordosis, pacing, locomotion, or place preference, the first pharmacological evidence that central melanocortin agonism modulates sexual desire specifically rather than reflexive sexual response.