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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]. | [in vivo]
Crotedumab (3-30 mg/kg; s.c. once weekly for 4 weeks) reduces blood glucose and body weight and induces reversible hyperglucagonemia and α-cell hyperplasia in DIO C57BL/6 mice[2].
Crotedumab (10 mg/kg; a single s.c.) markedly decreases blood glucose for 18 days in diabetic ob/ob mice[2].
REGN1193 (20 mg/kg; a single i.v.) produces a robust reduction in overnight-fasted blood glucose in both the conscious and anesthetized state of diabetic cynomolgus monkeys as well as in blood glucose measured 1 hour after feeding[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.
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| [References]
[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. DOI:10.1111/dom.13075
[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. DOI:10.1210/en.2015-1011 |
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