MBX-2982

"目录号: HY-15291

GPCR/G Protein-

MBX-2982 是一种口服选择性的 G 蛋白偶联受体 119 (GPR119) 激动剂。

GPR119

相关产品

AR 231453-PSN632408-APD597-GSK1292263-APD668-

生物活性

Description

MBX-2982 is a selective, orally-available G protein-coupled receptor 119 (GPR119) agonist.

IC50& Target

GPR119[1]

In Vitro

In cells pre-treated with MBX-2982 (1 μM) in “chronic incubation/washout” experiments, cAMP accumulation captured by IBMX inclusion is significantly increased compared to control cells (P<0.01; ANOVA; n=3-6) despite extensive washing to remove excess agonist. AR-231,453 produces sustained responses in a similar concentration range to those observed with acute stimulation (a small 1.82 fold shift), with pEC50s of 8.67±0.11 and 8.93±0.17, respectively. Likewise, a large but less severe shift in concentration responses (57.54 fold) is observed for MBX-2982 with respective sustained and acute pEC50s of 7.03±0.13 and 8.79±0.12[1].

In Vivo

To examine whether the observations in GLUTag and the primary intestinal cells has physiological relevance, C57BL/6 mice are treated with the GPR119 agonist MBX-2982 at a dose of 10 mg/kg. Note that in order to examine a direct GPR119 effect, no DPP-IV inhibitor is co-administered in this experiment, but a DPP-IV inhibitor is used to preserve active GLP-1 in the blood samples. The plasma GLP-1 levels from the mice dosed with MBX-2982 are increased without a glucose load, indicating that GPR119-mediated GLP-1 secretion is not dependent on glucose[2].

Clinical Trial

NCT01035879

CymaBay Therapeutics, Inc.

Diabetes

December 2009

Phase 2

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References

[1].Hothersall JD, et al. Sustained wash-resistant receptor activation responses of GPR119 agonists. Eur J Pharmacol. 2015 Sep 5;762:430-42.

[2].Lan H, et al. Agonists at GPR119 mediate secretion of GLP-1 from mouse enteroendocrine cells through glucose-independent pathways. Br J Pharmacol. 2012 Apr;165(8):2799-807.

[3].Yang JW, et al. GPR119: a promising target for nonalcoholic fatty liver disease. FASEB J. 2016 Jan;30(1):324-35.