Mavacamten-d5 (MYK461-d5; SAR439152-d5) is deuterium labeled Mavacamten . Mavacamten (MYK461) is an orally active modulator of cardiac myosin, with IC50s of 490, 711 nM for bovine cardiac and human cardiac, respectively.
Stable heavy isotopes of drogen, carbon, and other elements have been incorporated into drug molecules, largely as tracers for quantitation during the drug development process. Deuteration has gained attention because of its potential to affect the pharmacokinetic and metabolic profiles of drugs[1].
References:
[1]. Russak EM, et al. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019 Feb;53(2):211-216.
[2]. Kawas RF, et al. A small-molecule modulator of cardiac myosin acts on multiple stages of the myosin chemomechanical cycle. J Biol Chem. 2017 Oct 6;292(40):16571-16577.
[3]. Stern JA, et al. A Small Molecule Inhibitor of Sarcomere Contractility Acutely Relieves Left Ventricular Outflow Tract Obstruction in Feline pertrophic Cardiomyopat. PLoS One. 2016 Dec 14;11(12):e0168407.
[4]. Green EM, et al. A small-molecule inhibitor of sarcomere contractility suppresses pertrophic cardiomyopat in mice. Science. 2016 Feb 5;351(6273):617-21.