Rezubio Pharmaceuticals (宁康瑞珠) has filed the IND application for novel small-molecule gut-restricted GPR40 agonist RZ-629 in China. Rezubio Pharmaceuticals Co., Ltd is a biotech company founded by Yusheng Xiong and Hong-Ping Guan in Zhuhai, China.
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| Rezubio |
RZ-629
According to the ACS Meeting Spring 2024, RZ-629 is a novel gut-restricted membrane-anchored drug GPR40 agonist discovered by Rezubio. RZ-629 showed outstanding efficacy in both glucose and body weight reductions, with shallow blood exposure. The gut-restricted compound design effectively avoided liver and potential pancreas toxicities as nearly 100% of the parent drug was excreted in feces, with bile and urine accounting for less than 0.01% of the dose.
In 2020 and 2022, Rezubio filed patents (WO2023134712/WO2022028317) covering GPR40 agonists, which can be used for treating various disorders, conditions, or diseases such as Type 2 diabetes. In some examples, compounds covalently linked to the hydrophilic group T A have a similar EC50 or lower EC50 value. Below are some example compounds:
| Examples in patent |
In 2022, Yusheng Xiong and Hong-Ping Guan, the founders of Rezubio, authored a review in Front Pharmacol, discussing the recent progress., the possible mechanisms of the side effects in different organs, the possibility of developing novel strategies that retain the robust efficacy while avoiding toxicities caused by off-target and on-target mechanisms. E.g. by optimizing the compound's metabolic stability, we can preserve the compound's biological activity in the gut while significantly reducing systemic exposure due to its weak metabolic stability.
GPR40 Agonists in China
Chinese biotechs are being cautious about entering the area due to the increased risk of GPR40 development. Tasly obtained a license for Lilly's GPR40 agonist in 2018, but development was discontinued early in 2023.
Fuglifam
Fulglifam is a GPR40 agonist discovered by Hengrui as a fast-follow product of TAK-875. Progress has been stagnant, with three phase 1 trials being initiated in 2015-2016.
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