Cytokinetics Announces First Publication on Smooth Muscle Myosin Inhibitors in The Journal of Pharmacology and Experimental Therapeutics
Findings Demonstrate the Potential Therapeutic Application of Inhibitors of Smooth Muscle Myosin for the Treatment of Hypertension
Press Release Source: Cytokinetics, Inc. On Tuesday September 27, 2011, 7:30 am EDT
SOUTH SAN FRANCISCO, CA--(Marketwire -09/27/11)- Cytokinetics, Incorporated (NASDAQ: CYTK - News) announced the publication of preclinical research relating to its program directed to the inhibition of smooth muscle myosin as a novel therapeutic approach for the potential treatment of hypertension in the October 2011 issue of The Journal of Pharmacology and Experimental Therapeutics. This publication reveals, for the first time in a peer-reviewed journal, the role of inhibitors of smooth muscle myosin in preclinical models of hypertension.
"We are excited to have Cytokinetics' novel scientific research relating to inhibitors of smooth muscle myosin published in this prestigious journal," stated Fady I. Malik, MD, PhD, FACC, Cytokinetics' Vice President of Biology and Therapeutics. "This publication summarizes pioneering work performed by our research team to leverage our expertise in the biology of muscle function and establishes this novel mechanism as a potential approach to treating patients with hypertension."
The publication titled "Inhibition of Smooth Muscle Myosin as a Novel Therapeutic Target for Hypertension" discusses the potential application for therapies that directly inhibit smooth muscle myosin based on work in preclinical models of hypertension. In this publication, the authors compared the efficacy in conscious dogs with renal-induced hypertension of CK-2018488, a small molecule direct inhibitor of smooth muscle myosin, to that of a calcium channel blocker, amlodipine. Dogs were instrumented chronically for the measurement of arterial pressure, cardiac output and regional blood flow and hypertension induced. In the hypertensive state, mean arterial pressure increased from 101±3.8 to 142±1.9 mmHg. At the doses selected, CK-2018448 and amlodipine similarly increased cardiac output (30±11% vs. 33±6.4%) and similarly reduced mean arterial pressure (-22±3.6% vs. -16±3.4%) and total peripheral resistance (-36±5.9% vs. -37±5.8%). However, CK-2018448 had the greatest vasodilator effect in the renal bed, where renal blood flow increased by 46±9.0%, versus 11±3.4% for amlodipine (p < 0.01). CK-2018488 produced significantly less vasodilation in the limb, where iliac blood flow did not change; in contrast, it rose by 48±12% with amlodipine (p < 0.01). The authors noted that the minimal effects of CK-2018488 on limb blood flow could limit the development of peripheral edema, an adverse side effect of calcium channel blockers. Additionally, in a rodent model of hypertension, oral administration of this smooth muscle myosin inhibitor resulted in a sustained antihypertensive effect. Thus, the authors concluded that the preferential effect of smooth muscle myosin inhibition on renal blood flow may make this drug mechanism particularly appealing, since many patients with hypertension have renal insufficiency, and patients with heart failure could benefit from afterload reduction coupled with enhanced renal blood flow.
Background on Cytokinetics' Smooth Muscle Contractility Program
Cytokinetics' smooth muscle contractility research program is directed to smooth muscle myosin, the motor protein responsible for the contraction of the smooth muscle cells that surround airways in the lungs and the blood vessels that control blood pressure. By inhibiting the function of the myosin motor central to the contraction of smooth muscle, potent small molecules arising from this program may directly contribute to the relaxation of contracted smooth muscle. Cytokinetics' smooth muscle myosin inhibitors have demonstrated encouraging pharmacological activity in preclinical models that may relate to uses for the potential treatment of diseases such as asthma, chronic obstructive pulmonary disease (COPD) and systemic hypertension. Cytokinetics continues to conduct research and non-clinical development of its smooth muscle myosin inhibitors.
