GRA Ex-25 is a potent glucagon receptor inhibitor with IC50 of 56 and 55 nM for rat and human glucagon receptors, respectively. GRA Ex-25 binds to the human glucagon receptor (h-GlucRbind) with a Ki of 63 nM and moderates glucagon-induced adenylate cyclase inhibition (h-GlucRcyclase) with a Ki of 254 nM[2]. GRA Ex-25 has similar affinity for rat and human glucagon receptors (IC50 of 56 and 55 nM, respectively). GRA Ex-25 (3 mg/kg, iv) reduces blood glucose levels induced by exogenous glucagon in a rat model, possibly due to direct inhibition of glucagon-stimulated hepatic glucose output[2].
References:
[1]. Li L, Dai S, et,al . Antagonistic Effect and In Vitro Activity of Dauricine on Glucagon Receptor. J Nat Prod. 2022 Aug 26;85(8):2035-2043. doi: 10.1021/acs.jnatprod.2c00446. Epub 2022 Jul 14. PMID: 35834753.
[2].Lau J, Behrens C, et,al . New beta-alanine derivatives are orally available glucagon receptor antagonists. J Med Chem. 2007 Jan 11;50(1):113-28. doi: 10.1021/jm058026u. PMID: 17201415.
GRA Ex-25 是一种有效的胰高血糖素受体抑制剂，对大鼠和人类胰高血糖素受体的 IC50 分别为 56 和 55 nM。GRA Ex-25 与人类胰高血糖素受体 (h-GlucRbind) 结合，Ki 为 63 nM，并缓和胰高血糖素诱导的腺苷酸环化酶抑制 (h-GlucRcyclase)，Ki 为 254 nM[2]。GRA Ex-25 对大鼠和人类胰高血糖素受体具有相似的亲和力（IC50 分别为 56 和 55 nM）。GRA Ex-25（3 mg/kg，iv）降低大鼠模型中外源性胰高血糖素诱导的血糖水平，可能是由于直接抑制胰高血糖素刺激的肝葡萄糖输出[2]。