CK-2127107 增强了人类神经激活引起的骨骼肌反应。
CK-2127107 amplifies skeletal muscle response to nerve activation in humans.
机构信息
Cytokinetics, Inc., 280 East Grand Avenue, South San Francisco, California, 94080, USA.
Covance, Inc., Evansville, Indiana, USA.
出版信息
Muscle Nerve. 2018 May;57(5):729-734. doi: 10.1002/mus.26017. Epub 2017 Dec 11.
INTRODUCTION
Three studies evaluated safety, tolerability, pharmacokinetics, and pharmacodynamics of CK-2127107 (CK-107), a next-generation fast skeletal muscle troponin activator (FSTA), in healthy participants. We tested the hypothesis that CK-107 would amplify the force-frequency response of muscle in humans.
METHODS
To assess the force-frequency response, participants received single doses of CK-107 and placebo in a randomized, double-blind, 4-period, crossover study. The force-frequency response of foot dorsiflexion following stimulation of the deep fibular nerve to activate the tibialis anterior muscle was assessed.
RESULTS
CK-107 significantly increased tibialis anterior muscle response with increasing dose and plasma concentration in a frequency-dependent manner; the largest increase in peak force was ∼60% at 10 Hz.
DISCUSSION
CK-107 appears more potent and produced larger increases in force than tirasemtiv-a first-generation FSTA-in a similar pharmacodynamic study, thereby supporting its development for improvement of muscle function of patients. Muscle Nerve 57: 729-734, 2018.
简介
三项研究评估了新一代快速骨骼肌肌钙蛋白激活剂（FSTA）CK-2127107（CK-107）在健康参与者中的安全性、耐受性、药代动力学和药效学。我们检验了如下假说，即 CK-107 将增强人类肌肉的力频率反应。
方法
为了评估力频率反应，参与者在一项随机、双盲、4 期交叉研究中接受了 CK-107 和安慰剂的单次剂量。通过刺激腓深神经来激活胫骨前肌，评估足背屈的力频率反应。
结果
CK-107 以频率依赖性的方式显著增加了胫骨前肌的反应，随着剂量和血浆浓度的增加而增加；在 10 Hz 时，最大峰值力增加约 60%。
讨论
在一项类似的药效学研究中，CK-107 比第一代 FSTA 替瑞斯美汀显示出更强的效力，并产生更大的力增加，从而支持其开发用于改善患者的肌肉功能。肌肉神经 57：729-734，2018 年。
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