GCGR antagonist 2

Names

[ CAS No. ]:
280134-25-0

[ Name ]:
GCGR antagonist 2

Biological Activity

[Description]:

GCGR antagonist 2, a Furan-2-carbohydrazide, is an orally active glucagon receptor antagonist. GCGR antagonist 2 binds to hGluR with an Kd value of 2.3 nM, and inhibits rat receptor with an IC50 value of 0.43 nM. GCGR antagonist 2 inhibits glucagon-stimulated glycogenolysis[1][2].

[Related Catalog]:

Research Areas >> Metabolic Disease

[In Vitro]

GCGR antagonist 2 (化合物 74) (25 nM, 250 nM 和 2500 nM；70 min) 抑制 5 nM 胰高血糖素诱导的原代大鼠肝细胞糖原分解，IC50 为 160 nM[1]。 GCGR antagonist 2 (25 nM, 250 nM 和 2500 nM；60 min) 在 BHK 细胞中，抑制重组人胰高血糖素受体抑制胰高血糖素刺激的 cAMP 水平[1]。 GCGR antagonist 2 (1 nM, 10 nM 和100 nM；60 min) 抑制分离的大鼠肝脏胰高血糖素受体抑制 BHK 细胞中胰高血糖素刺激的 cAMP 水平[1]。

[In Vivo]

GCGR antagonist 2 (0.5 mg/kg 静脉注射，或 2 mg/kg 口服；单次剂量) 的平均半衰期分别为 1.11 h 和 1.40 h[1]。 GCGR antagonist 2 (0 mg/kg, 3 mg/kg 和 10 mg/kg；口服) 在受胰高血糖素刺激的 Sprague-Dawley 大鼠中，至少部分地抑制了内源性胰高血糖素，并维持正糖状态[1]。

[References]

[1]. Madsen P, et al. Optimization of alkylidene hydrazide based human glucagon receptor antagonists. Discovery of the highly potent and orally available 3-cyano-4-hydroxybenzoic acid [1-(2,3,5,6-tetramethylbenzyl)-1H-indol-4-ylmethylene]hydrazide. J Med Chem. 2002 Dec 19;45(26):5755-75.  

[2]. Hasegawa F, et al. Discovery of furan-2-carbohydrazides as orally active glucagon receptor antagonists. Bioorg Med Chem Lett. 2014 Sep 1;24(17):4266-70.  

Chemical & Physical Properties

[ Molecular Formula ]:
C28H26N4O2

[ Molecular Weight ]:
450.53200

[ Exact Mass ]:
450.20600

[ PSA ]:
93.90000

[ LogP ]:
5.83918

Related Compounds