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Cytokinetics Announces Preclinical Data for CK-3773274 Presented at the Biophysical Society 64th Annual Meeting
Preclinical Studies Demonstrate Distinct Binding Site for Next-Generation Cardiac Myosin Inhibitor SOUTH SAN FRANCISCO, Calif., Feb. 20, 2020 (GLOBE NEWSWIRE)
About this update from Cytokinetics, Incorporated
[{"type":"text","content":"Preclinical Studies Demonstrate Distinct Binding Site for Next-Generation Cardiac Myosin Inhibitor\nSOUTH SAN FRANCISCO, Calif., Feb. 20, 2020 (GLOBE NEWSWIRE) -- Cytokinetics, Incorporated (Nasdaq: CYTK) today announced that preclinical data related to CK-3773274 (CK-274) were presented at the Biophysical Society 64th Annual Meeting in San Diego, CA elaborating on its mechanism of action and properties to modulate cardiac contractility in vitro and in vivo. CK-274 is a next-generation cardiac myosin inhibitor discovered by company scientists, in development for the potential treatment of hypertrophic cardiomyopathy (HCM).\n “These data further characterize how CK-274 decreases cardiac contractility in vitro and in vivo, and provide evidence for a distinct and selective mechanistic binding site for CK-274 on cardiac myosin,” said Brad Morgan, Ph.D., Cytokinetics’ Senior Vice President, Research and Non-Clinical Development. “We are pleased to contribute these preclinical data supporting translation of cardiac myosin inhibition as a novel approach to the potential treatment of diseases associated with hypercontractility as we conduct REDWOOD-HCM, the Phase 2 clinical trial of CK-274 in patients with obstructive hypertrophic cardiomyopathy.” Preclinical Research Data Presented at Biophysical Society Annual Meeting Previous in vitro and in vivo studies have shown that CK-274 reduced cardiac contractility and reduced fractional shortening (a measure of cardiac function) in a dose and concentration dependent manner. New data presented at the Biophysical Society Annual Meeting demonstrate that CK-274 reduces cardiac myosin activity in vitro, and importantly it does not inhibit the actin-activated ATPase activity of smooth muscle myosin, supportive of its selectivity for cardiac myosin. Transient kinetic studies also show that CK-274 slows the rate of actin-activated phosphate release, without affecting ATP binding and hydrolysis, consistent with a mechanism that stabilizes myosin in weak actin-binding conformations. Additionally, the binding of CK-274 to cardiac myosin is shown to be mutually exclusive with the non-selective myosin inhibitor blebbistatin, thus suggesting they bind to the same or overlapping locations on cardiac myosin, but distinctly from one another given the differences in their selectivity for cardiac myosin. In co...