1228561-27-0Relevant articles and documents
Discovery of Aficamten (CK-274), a Next-Generation Cardiac Myosin Inhibitor for the Treatment of Hypertrophic Cardiomyopathy
Ashcraft, Luke,Chin, Eva R.,Chuang, Chihyuan,Collibee, Scott,Cremin, Peadar,Hartman, James,Hwee, Darren T.,Malik, Fady I.,Morgan, Bradley P.,Robertson, Laura A.,Schaletzky, Julia,Vander Wal, Mark,Wang, Jingying,Wang, Wenyue,Wang, Xiaolin,Wehri, Eddie,Wu, Yangsong,Zamora, Jeanelle
supporting information, p. 14142 - 14152 (2021/10/20)
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 1. The important advancement of the optimization was discovery of an Indane analogue (12) with a less restrictive structure-activity relationship that allowed for the rapid improvement of drug-like properties. Aficamten was designed to provide a predicted human half-life (t1/2) appropriate for once a day (qd) dosing, to reach steady state within two weeks, to have no substantial cytochrome P450 induction or inhibition, and to have a wide therapeutic window in vivo with a clear pharmacokinetic/pharmacodynamic relationship. In a phase I clinical trial, aficamten demonstrated a human t1/2 similar to predictions and was able to reach steady state concentration within the desired two-week window.
USE OF GHRELIN RECEPTOR INVERSE AGONISTS OR ANTAGONISTS FOR TREATING SLEEP DISORDERS
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Page/Page column 17, (2014/01/08)
The present invention relates to methods of treating sleep disorders in patients comprising administration of a ghrelin receptor inverse agonist or antagonist. The invention also includes methods of treating sleep disorders comprising the administration of a pharmaceutical composition comprising a ghrelin receptor inverse agonist or antagonist and at least one pharmaceutically acceptable carrier, diluent, or excipient.