Nature Study Reveals: AI and Molecular Dynamics Designed BGM0504 Exhibits Superior Potency

BGM0504, an AI-assisted designed dual GIP and GLP-1 receptor agonist, demonstrates superior efficacy in both in vitro and in vivo experiments. Using AI-driven computer simulations, Bright Gene has discovered that optimal interaction between the glutamate residues on both GLP-1R and GIPR and the K20 residue of a peptide agonist provide superior activity. This interaction is a key insight not evident in cryo-EM studies. BGM0504 was designed to preserve the free amino group of the K20 residue by shifting the acylation point to position 40 of BGM0504. This design resulted in a 3-fold increase in agonistic effects on GLP-1R and GIPR, with superior therapeutic outcomes in diabetic and obesity mouse models.

BGM0504, an AI-assisted designed dual GIP and GLP-1 receptor agonist, demonstrates superior efficacy in both in vitro and in vivo experiments. Using AI-driven computer simulations, Bright Gene has discovered that optimal interaction between the glutamate residues on both GLP-1R and GIPR and the K20 residue of a peptide agonist provide superior activity. This interaction is a key insight not evident in cryo-EM studies. BGM0504 was designed to preserve the free amino group of the K20 residue by shifting the acylation point to position 40 of BGM0504. This design resulted in a 3-fold increase in agonistic effects on GLP-1R and GIPR, with superior therapeutic outcomes in diabetic and obesity mouse models.

About Bright Gene and BGM0504

Bright Gene (Stock Code: 688166.SH) is an innovative pharmaceutical company focused on developing best-in-class pharmaceuticals. The company integrates APIs and formulations, combining generic and innovative drugs to meet global clinical needs. BGM0504 is a dual GIP/GLP-1 receptor agonist for treating type 2 diabetes, obesity, and NASH, currently in the late stages of Phase II clinical trials.

Reference

Yuan, J., Liu, W., Jiang, X. et al. Molecular dynamics-guided optimization of BGM0504 enhances dual-target agonism for combating diabetes and obesity. Sci Rep 14, 16680 (2024). https://doi.org/10.1038/s41598-024-66998-8

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