Molecular mechanism
Glucagon receptor
GCGR is a class B G-protein-coupled receptor. Retatrutide's LY3437943 discovery record characterizes a molecular agonist relationship at GCGR alongside GIPR and GLP-1R.
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Neutral molecular overview
GCGR is a class B G-protein-coupled receptor. Retatrutide's LY3437943 discovery record characterizes a molecular agonist relationship at GCGR alongside GIPR and GLP-1R.
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Target identifiers
No target identifier beyond the verified name and aliases is declared in this Phase 1A record.
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Related compounds
Compound
Glucagon
Glucagon is the endogenous 29-residue pancreatic hormone and the native ligand of the glucagon receptor.
Compound
Mazdutide
Mazdutide is a lipidated synthetic peptide classified as a GLP-1 and glucagon receptor dual agonist, built on an oxyntomodulin-derived backbone.
Compound
Oxyntomodulin
Oxyntomodulin is an endogenous proglucagon-derived peptide containing the complete glucagon sequence plus an eight-residue C-terminal extension, with reported activity at both the GLP-1 and glucagon receptors.
Compound
Retatrutide
Retatrutide, development code LY3437943, is a single peptide characterized as an agonist at GCGR, GIPR, and GLP-1R in its discovery record.
Compound
Survodutide
Survodutide is a lipidated synthetic peptide agonist at both the GLP-1 receptor and the glucagon receptor, built on a modified glucagon-family backbone with a branched side-chain linker.
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Related mechanisms
receptor
Glucagon-like peptide-1 receptor
GLP-1R is a class B G-protein-coupled receptor. The cited structural and pharmacology records characterize semaglutide and retatrutide as peptide agonists at this receptor.
receptor
Glucose-dependent insulinotropic polypeptide receptor
GIPR is a class B G-protein-coupled receptor. The cited discovery and trial records identify it as one of the three receptor relationships declared for retatrutide.
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Verified bibliography
- LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept.current
Coskun T, Urva S, Roell WC, Qu H, Loghin C, Moyers JS, O'Farrell LS, Briere DA, Sloop KW, Thomas MK, Pirro V, Wainscott DB, Willard FS, Abernathy M, Morford L, Du Y, Benson C, Gimeno RE, Haupt A, Milicevic Z
Cell metabolism · 2022-08-18 · Journal Article
- Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial.current
Jastreboff AM, Kaplan LM, Frías JP, Wu Q, Du Y, Gurbuz S, Coskun T, Haupt A, Milicevic Z, Hartman ML, Retatrutide Phase 2 Obesity Trial Investigators
The New England journal of medicine · 2023-06-26 · Clinical Trial, Phase II
- Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA.current
Rosenstock J, Frias J, Jastreboff AM, Du Y, Lou J, Gurbuz S, Thomas MK, Hartman ML, Haupt A, Milicevic Z, Coskun T
Lancet (London, England) · 2023-06-26 · Clinical Trial, Phase II
- Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial.current
Sanyal AJ, Kaplan LM, Frias JP, Brouwers B, Wu Q, Thomas MK, Harris C, Schloot NC, Du Y, Mather KJ, Haupt A, Hartman ML
Nature medicine · 2024-06-10 · Clinical Trial, Phase II
- Structure of the full-length glucagon class B G-protein-coupled receptor.current
Zhang H, Qiao A, Yang D, Yang L, Dai A, de Graaf C, Reedtz-Runge S, Dharmarajan V, Zhang H, Han GW, Grant TD, Sierra RG, Weierstall U, Nelson G, Liu W, Wu Y, Ma L, Cai X, Lin G, Wu X, Geng Z, Dong Y, Song G, Griffin PR, Lau J, Cherezov V, Yang H, Hanson MA, Stevens RC, Zhao Q, Jiang H, Wang MW, Wu B
Nature · 2017-05-17 · Journal Article
- Structure of the glucagon receptor in complex with a glucagon analogue.current
Zhang H, Qiao A, Yang L, Van Eps N, Frederiksen KS, Yang D, Dai A, Cai X, Zhang H, Yi C, Cao C, He L, Yang H, Lau J, Ernst OP, Hanson MA, Stevens RC, Wang MW, Reedtz-Runge S, Jiang H, Zhao Q, Wu B
Nature · 2018-01-03 · Journal Article
- BI 456906: Discovery and preclinical pharmacology of a novel GCGR/GLP-1R dual agonist with robust anti-obesity efficacy.current
Zimmermann T, Thomas L, Baader-Pagler T, Haebel P, Simon E, Reindl W, Bajrami B, Rist W, Uphues I, Drucker DJ, Klein H, Santhanam R, Hamprecht D, Neubauer H, Augustin R
Molecular metabolism · 2022-11-07 · Journal Article
- The dual GCGR/GLP-1R agonist survodutide: Biomarkers and pharmacological profiling for clinical candidate selection.current
Thomas L, Martel E, Rist W, Uphues I, Hamprecht D, Neubauer H, Augustin R
Diabetes, obesity & metabolism · 2024-04-01 · Journal Article
- Structural analysis of the dual agonism at GLP-1R and GCGR.current
Li Y, Zhou Q, Dai A, Zhao F, Chang R, Ying T, Wu B, Yang D, Wang MW, Cong Z
Proceedings of the National Academy of Sciences of the United States of America · 2023-08-07 · Journal Article
- Evaluation of biased agonism mediated by dual agonists of the GLP-1 and glucagon receptors.current
Darbalaei S, Yuliantie E, Dai A, Chang R, Zhao P, Yang D, Wang MW, Sexton PM, Wootten D
Biochemical pharmacology · 2020-07-17 · Journal Article
- Partial agonism improves the anti-hyperglycaemic efficacy of an oxyntomodulin-derived GLP-1R/GCGR co-agonist.current
Pickford P, Lucey M, Rujan RM, McGlone ER, Bitsi S, Ashford FB, Corrêa IR, Hodson DJ, Tomas A, Deganutti G, Reynolds CA, Owen BM, Tan TM, Minnion J, Jones B, Bloom SR
Molecular metabolism · 2021-04-30 · Journal Article
- Structural basis of G(s) and G(i) recognition by the human glucagon receptor.current
Qiao A, Han S, Li X, Li Z, Zhao P, Dai A, Chang R, Tai L, Tan Q, Chu X, Ma L, Thorsen TS, Reedtz-Runge S, Yang D, Wang MW, Sexton PM, Wootten D, Sun F, Zhao Q, Wu B
Science (New York, N.Y.) · 2020-03-20 · Journal Article
- The glucagon receptor is involved in mediating the body weight-lowering effects of oxyntomodulin.current
Kosinski JR, Hubert J, Carrington PE, Chicchi GG, Mu J, Miller C, Cao J, Bianchi E, Pessi A, Sinharoy R, Marsh DJ, Pocai A
Obesity (Silver Spring, Md.) · 2012-03-16 · Journal Article
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Related glossary terms
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