Lot certificates published
Plain, secure packaging
Purely Peptides
Research Catalog

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.

Type: receptorPublished: 2026-09-04Literature/identifier verification: 2026-08-23

See this target on the receptor map

GCGR

01

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.

02

Target identifiers

No target identifier beyond the verified name and aliases is listed for this mechanism.

03

Related compounds

Compound

Glucagon

Glucagon is the endogenous 29-residue pancreatic hormone and the native ligand of the glucagon receptor. Horváth et al. (PMID 37528104) place glucagon among the gastrointestinal peptides of the glucagon family.

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. A review by Bataille and Dalle (PMID 25115338) describes oxyntomodulin as a member of the glucagon family; that is a review-level family attribution.

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.

04

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.

05

Verified bibliography

  1. Reference 1

    LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept.

    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

    current
    PMID 35985340DOI 10.1016/j.cmet.2022.07.013RetatrutideGLP-1RGIPRGCGR

  2. Reference 2

    Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial.

    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

    current
    PMID 37366315DOI 10.1056/NEJMoa2301972RetatrutideGLP-1RGIPRGCGR

  3. Reference 3

    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.

    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

    current
    PMID 37385280DOI 10.1016/S0140-6736(23)01053-XRetatrutideGLP-1RGIPRGCGR

  4. Reference 4

    Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial.

    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

    current
    PMID 38858523PMC11271400DOI 10.1038/s41591-024-03018-2RetatrutideGLP-1RGIPRGCGR

  5. Reference 5

    Structure of the full-length glucagon class B G-protein-coupled receptor.

    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

    current
    PMID 28514451PMC5492955DOI 10.1038/nature22363RetatrutideGCGR

  6. Reference 6

    Structure of the glucagon receptor in complex with a glucagon analogue.

    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

    current
    PMID 29300013DOI 10.1038/nature25153RetatrutideGCGR

  7. Reference 7

    BI 456906: Discovery and preclinical pharmacology of a novel GCGR/GLP-1R dual agonist with robust anti-obesity efficacy.

    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

    current
    PMID 36356832PMC9679702DOI 10.1016/j.molmet.2022.101633SurvodutideGlucagonGLP-1RGCGR

  8. Reference 8

    The dual GCGR/GLP-1R agonist survodutide: Biomarkers and pharmacological profiling for clinical candidate selection.

    Thomas L, Martel E, Rist W, Uphues I, Hamprecht D, Neubauer H, Augustin R

    Diabetes, obesity & metabolism · 2024-04-01 · Journal Article

    current
    PMID 38560764DOI 10.1111/dom.15551SurvodutideGLP-1RGCGR

  9. Reference 9

    Structural analysis of the dual agonism at GLP-1R and GCGR.

    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

    current
    PMID 37549266PMC10438375DOI 10.1073/pnas.2303696120SurvodutideMazdutideGLP-1RGCGR

  10. Reference 10

    Evaluation of biased agonism mediated by dual agonists of the GLP-1 and glucagon receptors.

    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

    current
    PMID 32682761DOI 10.1016/j.bcp.2020.114150MazdutideGLP-1RGCGR

  11. Reference 11

    Partial agonism improves the anti-hyperglycaemic efficacy of an oxyntomodulin-derived GLP-1R/GCGR co-agonist.

    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

    current
    PMID 33933675PMC8163982DOI 10.1016/j.molmet.2021.101242MazdutideGLP-1RGCGR

  12. Reference 12

    Structural basis of G(s) and G(i) recognition by the human glucagon receptor.

    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

    current
    PMID 32193322DOI 10.1126/science.aaz5346GlucagonGCGR

  13. Reference 13

    The glucagon receptor is involved in mediating the body weight-lowering effects of oxyntomodulin.

    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

    current
    PMID 22421924PMC3408645DOI 10.1038/oby.2012.67OxyntomodulinGLP-1RGCGR

Study models of these references

What kind of experiment each cited paper reports, taken from its abstract unless marked. Not a summary of results.

ReferenceStudy models
Coskun T et al. 2022Study models reported: in vitro; animal (mouse); human participants (interventional) · from the abstract
Jastreboff AM et al. 2023Study models reported: human participants (interventional) · from the abstract
Rosenstock J et al. 2023Study models reported: human participants (interventional) · from the abstract
Sanyal AJ et al. 2024Study models reported: human participants (interventional) · from the abstract
Zhang H et al. 2017Study models reported: in vitro · from the abstract
Zhang H et al. 2018Study models reported: in vitro · from the abstract
Zimmermann T et al. 2022Study models reported: in vitro; animal (mouse, beagle dog) · from the full text
Thomas L et al. 2024Study models reported: in vitro; animal (mouse) · from the abstract
Li Y et al. 2023Study models reported: in vitro · from the abstract
Darbalaei S et al. 2020Study models reported: in vitro · from the abstract
Pickford P et al. 2021Study models reported: in vitro; animal (mouse) · from the abstract
Qiao A et al. 2020Study models reported: in vitro · from the abstract
Kosinski JR et al. 2012Study models reported: in vitro; animal (mouse) · from the full text

06

Related glossary terms

AgonistLigandG-protein-coupled receptor

07

Related Purely Peptides research articles