Aficamten (CK-274) is a potent cardiac myosin inhibitor with an IC50 of 1.4 μM, suitable for researching hypertrophic cardiomyopathy (HCM) [1].
体内研究
Aficamten is a next-generation cardiac myosin inhibitor designed for once-daily dosing with a suitable projected human half-life. It reaches a steady state within two weeks and offers a broad therapeutic window in vivo, along with a well-defined pharmacokinetic/pharmacodynamic (PK/PD) relationship [1].
Aficamten shows moderate oral bioavailability following administration, with rates of 98% in mice, 55% to 79% in rats, 45% in dogs, and 41% in monkeys. These figures are based on doses of 1 mg/kg in mice, 2 mg/kg to 8 mg/kg in rats, 1 mg/kg in dogs, and 1 mg/kg in monkeys [1].
Aficamten demonstrates terminal elimination half-lives of 4.5 hours in mice, 3.0 hours in rats, 33.8 hours in dogs, and 8.1 hours in monkeys following intravenous administration at doses of 0.5 mg/kg in mice, 1 mg/kg in rats and dogs, and 1.0 mg/kg in monkeys [1].
Aficamten 细胞实验
Cell Line
Concentration
Treated Time
Description
References
chicken gizzard SMM S1
1 µM
Did not significantly inhibit smooth muscle S1 ATPase activity.
Dose-dependent reduction in cardiac contractility, returned to baseline within 24 hours.
Nat Cardiovasc Res. 2024 Aug;3(8):1003-1016
Cats
A31P MYBPC3 mutation hypertrophic cardiomyopathy cat model
Oral
2 mg/kg
Single dose, 48-hour observation
To evaluate the effects of Aficamten on cardiac function in cats with hypertrophic cardiomyopathy. Results showed that high-dose Aficamten (2 mg/kg) reduced left ventricular fractional shortening (LVFS%) by increasing the LV systolic internal dimension (LVIDs) and reduced isovolumic relaxation time (IVRT) compared with baseline without significant adverse effects.
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