In vitro and in vivo preclinical pharmacokinetic characterization of aficamten, a small molecule cardiac myosin inhibitor.

Aficamten, a small molecule selective inhibitor of cardiac myosin, was characterised in preclinical and studies.Protein binding in human plasma was 10.4% unbound and ranged from 1.

Discovery of Aficamten (CK-274), a Next-Generation Cardiac Myosin Inhibitor for the Treatment of Hypertrophic Cardiomyopathy.

Hypercontractility of the cardiac sarcomere may be essential for the underlying pathological hypertrophy and fibrosis in genetic hypertrophic cardiomyopathies. Aficamten (CK-274) is a novel cardiac myosin inhibitor that was discovered from the optimization of indoline compound . The important advancement of the optimization was discovery of an Indane analogue () with a less restrictive structure-activity relationship that allowed for the rapid improvement of drug-like properties.

Arbaclofen placarbil, a novel R-baclofen prodrug: improved absorption, distribution, metabolism, and elimination properties compared with R-baclofen.

Baclofen is a racemic GABA(B) receptor agonist that has a number of significant pharmacokinetic limitations, including a narrow window of absorption in the upper small intestine and rapid clearance from the blood. Arbaclofen placarbil is a novel transported prodrug of the pharmacologically active R-isomer of baclofen designed to be absorbed throughout the intestine by both passive and active mechanisms via the monocarboxylate type 1 transporter. Arbaclofen placarbil is rapidly converted to R-baclofen in human and animal tissues in vitro.