ArticleJournal of medicinal chemistry2026
Discovery of AMG 133, a Glucose-Dependent Insulinotropic Polypeptide Receptor Antagonist and Glucagon-Like Peptide 1 Receptor Agonist Antibody-Drug Conjugate for the Treatment of Obesity.
Article in Journal of medicinal chemistry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
1 citing paper in PubMed.
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Authors and funding
20 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Multispecific therapeutics represent an increasingly important approach for enhancing the efficacy in complex diseases. Here, we report the design and optimization of novel antibody-peptide conjugates that combine glucose-dependent insulinotropic polypeptide receptor (GIPR) antagonism with glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) agonism for the treatment of obesity. A series of hybrid molecules was generated by conjugating synthetic GLP-1 peptides to IgG-based anti-GIPR antibodies, yielding markedly prolonged systemic exposure of the structurally intact GLP-1 peptide. In diet-induced obese mice and obese monkeys, once weekly administration of anti-GIPR-Ab/GLP-1 conjugates produced sustained body weight loss and improvements in metabolic parameters. This optimization effort culminated in the discovery of AMG 133, currently in phase III clinical trials with a profile that may support monthly dosing.
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