Crotedumab

Crotedumab (REGN1193) is a fully human IgG4 monoclonal antibody that binds and inhibits glucagon receptor (GCGR), with a KD of 0.1 nM. Crotedumab can be used for the research of diabetes[1][2].

Research Areas >> Metabolic Disease

KD: 0.1 nM[2]

Crotedumab 以高亲和力 (KD=0.03 nM-0.39 nM) 结合来自多个物种 (小鼠、大鼠、猴子和人类) 的 GCGR[2]。 Crotedumab 通过 GCGR 抑制转染人、猴、小鼠和大鼠 GCGR 的 HEK293 细胞中胰高血糖素诱导的信号传导，IC50 值分别为 0.65，3.2，0.94 和 1.0 nM[2 ]。

Crotedumab (3-30 mg/kg; 皮下注射，每周一次，持续 4 周) 可降低饮食引起的肥胖小鼠的血糖和体重，并诱导可逆性高胰高血糖素血症和 α 细胞增生[2]。 Crotedumab (10 mg/kg; 单次皮下注射) 持续 18 天显着降低糖尿病 ob/ob 小鼠的血糖[2]。 REGN1193 (20 mg/kg; 单次静脉注射) 可显着降低糖尿病食蟹猴意识和麻醉状态下的夜间空腹血糖以及进食后 1 小时测量的血糖[2]。 Animal Model: Diet-induced obese (DIO) male C57BL/6NTac mice were maintained on high-fat diet[2] Dosage: 3, 10, 30 mg/kg Administration: S.c. injection once weekly for 4 weeks Result: Markedly reduced blood glucose throughout the dosing period. Reversibly decreased body weight during the dosing period. Dose- and time-dependently increased glucagon and GLP-1. Reversibly increased α-cell area.

[1]. Kostic A, et, al. A first-in-human pharmacodynamic and pharmacokinetic study of a fully human anti-glucagon receptor monoclonal antibody in normal healthy volunteers. Diabetes Obes Metab. 2018 Feb;20(2):283-291.  

[2]. Okamot H, et, al. Glucagon Receptor Blockade With a Human Antibody Normalizes Blood Glucose in Diabetic Mice and Monkeys. Endocrinology. 2015 Aug;156(8):2781-94.