Molecular mechanism
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.
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Neutral molecular overview
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.
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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
Exenatide
Exenatide is a 39-residue peptide with an N-terminal histidine and a C-terminal serine amide, originally isolated from Heloderma suspectum venom and characterized as a member of the glucagon superfamily.
Compound
GLP-1(7-36) amide
GLP-1(7-36) amide is an endogenous processing form of glucagon-like peptide-1 and the native ligand against which the GLP-1 receptor agonists in this library are compared.
Compound
GLP-1(7-37)
GLP-1(7-37) is an endogenous processing form of glucagon-like peptide-1 retaining a C-terminal glycine, and the structural reference for several acylated GLP-1 analogs.
Compound
Liraglutide
Liraglutide is an acylated peptide analog of glucagon-like peptide-1, characterized against the GLP-1 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
Orforglipron
Orforglipron is a synthetic nonpeptide molecule characterized as a selective, high-affinity agonist at the human GLP-1 receptor.
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
Semaglutide
Semaglutide is an acylated peptide analog of glucagon-like peptide-1. Its discovery record identifies two amino-acid substitutions and derivatization at Lys26.
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.
Compound
Tirzepatide
Tirzepatide is a fatty-acid-modified synthetic peptide characterized in its discovery record as having agonist activity at both the GIP receptor and the GLP-1 receptor.
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Related mechanisms
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.
receptor
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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Verified bibliography
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Lau J, Bloch P, Schäffer L, Pettersson I, Spetzler J, Kofoed J, Madsen K, Knudsen LB, McGuire J, Steensgaard DB, Strauss HM, Gram DX, Knudsen SM, Nielsen FS, Thygesen P, Reedtz-Runge S, Kruse T
Journal of medicinal chemistry · 2015-09-11 · Journal Article
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Zhang X, Belousoff MJ, Liang YL, Danev R, Sexton PM, Wootten D
Cell reports · 2021-07-13 · Journal Article
- The Discovery and Development of Liraglutide and Semaglutide.current
Knudsen LB, Lau J
Frontiers in endocrinology · 2019-04-12 · Review
- 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
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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
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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
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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
- Pharmacology, physiology, and mechanisms of incretin hormone action.current
Campbell JE, Drucker DJ
Cell metabolism · 2013-05-16 · Review
- Cryo-EM structure of the activated GLP-1 receptor in complex with a G protein.current
Zhang Y, Sun B, Feng D, Hu H, Chu M, Qu Q, Tarrasch JT, Li S, Sun Kobilka T, Kobilka BK, Skiniotis G
Nature · 2017-05-24 · Journal Article
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Underwood CR, Parthier C, Reedtz-Runge S
Vitamins and hormones · 2010 · Review
- Full-length human GLP-1 receptor structure without orthosteric ligands.current
Wu F, Yang L, Hang K, Laursen M, Wu L, Han GW, Ren Q, Roed NK, Lin G, Hanson MA, Jiang H, Wang MW, Reedtz-Runge S, Song G, Stevens RC
Nature communications · 2020-03-09 · Journal Article
- Structural basis for GLP-1 receptor activation by LY3502970, an orally active nonpeptide agonist.current
Kawai T, Sun B, Yoshino H, Feng D, Suzuki Y, Fukazawa M, Nagao S, Wainscott DB, Showalter AD, Droz BA, Kobilka TS, Coghlan MP, Willard FS, Kawabe Y, Kobilka BK, Sloop KW
Proceedings of the National Academy of Sciences of the United States of America · 2020-11-11 · 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
- Isolation and characterization of exendin-4, an exendin-3 analogue, from Heloderma suspectum venom. Further evidence for an exendin receptor on dispersed acini from guinea pig pancreas.current
Eng J, Kleinman WA, Singh L, Singh G, Raufman JP
The Journal of biological chemistry · 1992-04-15 · Journal Article
- current
- The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss.current
Secher A, Jelsing J, Baquero AF, Hecksher-Sørensen J, Cowley MA, Dalbøge LS, Hansen G, Grove KL, Pyke C, Raun K, Schäffer L, Tang-Christensen M, Verma S, Witgen BM, Vrang N, Bjerre Knudsen L
The Journal of clinical investigation · 2014-09-09 · Journal Article
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Coskun T, Sloop KW, Loghin C, Alsina-Fernandez J, Urva S, Bokvist KB, Cui X, Briere DA, Cabrera O, Roell WC, Kuchibhotla U, Moyers JS, Benson CT, Gimeno RE, D'Alessio DA, Haupt A
Molecular metabolism · 2018-10-03 · Journal Article
- Semaglutide lowers body weight in rodents via distributed neural pathways.current
Gabery S, Salinas CG, Paulsen SJ, Ahnfelt-Rønne J, Alanentalo T, Baquero AF, Buckley ST, Farkas E, Fekete C, Frederiksen KS, Helms HCC, Jeppesen JF, John LM, Pyke C, Nøhr J, Lu TT, Polex-Wolf J, Prevot V, Raun K, Simonsen L, Sun G, Szilvásy-Szabó A, Willenbrock H, Secher A, Knudsen LB, Hogendorf WFJ
JCI insight · 2020-03-26 · Journal Article
- How May GIP Enhance the Therapeutic Efficacy of GLP-1?current
Samms RJ, Coghlan MP, Sloop KW
Trends in endocrinology and metabolism: TEM · 2020-03-16 · Review
- Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist.current
Willard FS, Douros JD, Gabe MB, Showalter AD, Wainscott DB, Suter TM, Capozzi ME, van der Velden WJ, Stutsman C, Cardona GR, Urva S, Emmerson PJ, Holst JJ, D'Alessio DA, Coghlan MP, Rosenkilde MM, Campbell JE, Sloop KW
JCI insight · 2020-09-03 · Journal Article
- Structural determinants of dual incretin receptor agonism by tirzepatide.current
Sun B, Willard FS, Feng D, Alsina-Fernandez J, Chen Q, Vieth M, Ho JD, Showalter AD, Stutsman C, Ding L, Suter TM, Dunbar JD, Carpenter JW, Mohammed FA, Aihara E, Brown RA, Bueno AB, Emmerson PJ, Moyers JS, Kobilka TS, Coghlan MP, Kobilka BK, Sloop KW
Proceedings of the National Academy of Sciences of the United States of America · 2022-03-25 · Journal Article
- The pharmacological basis for nonpeptide agonism of the GLP-1 receptor by orforglipron.current
Sloop KW, Cox AL, Wainscott DB, White A, Droz BA, Stutsman C, Showalter AD, Suter TM, Dunbar JD, Snider BM, O'Farrell LS, Hewitt N, Ruble JC, Padgett LR, Woerly EM, Peterson JA, Coskun T, Liu Z, Coutant DE, Ai M, Emmerson PJ, Sangwung P, Willard FS
Science translational medicine · 2024-12-18 · Journal Article
- The glucagon receptor is involved in mediating the body weight-lowering effects of oxyntomodulin.current
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Related glossary terms
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