Tirasemtiv (CK-2017357)(CK 2017357) is a small-molecule fast-skeletal-troponin activator, with a potential treatment for muscle weakness and neuromuscular dysfunction.

Tirasemtiv acts as a fast skeletal troponin activator, enhancing the sarcomere's sensitivity to calcium, thereby magnifying muscle force production in response to diminished neuromuscular input. It specifically increases fast skeletal muscle troponin's responsiveness to calcium (Ca2+), and decelerates the Ca2+ dissociation from the fast skeletal muscle's regulatory troponin complex[1].

A single administration of Tirasemtiv significantly enhances muscle strength and endurance—as evidenced by improvements in submaximal isometric force, forelimb grip strength, grid hang time, and rotarod performance—in a female B6SJL-SOD1 g93A transgenic mouse model of ALS exhibiting functional deficits. This treatment also notably increases diaphragm force and tidal volume in these mice. Specifically, Tirasemtiv-treated mice showed a 38% increase in grip strength, rising from 49.6±4.6 g in vehicle-treated mice to 68.6±8.1 g, a statistically significant enhancement (p<0.05, single tailed t-test). The administered dosage regimen of Tirasemtiv was 2 mg/kg at approximately 20-minute intervals, totaling a cumulative dose of 10 mg/kg. Regression analysis further confirmed the efficacy of Tirasemtiv, showing a significant increase in muscle force not only in normal (WT) mice but also in B6SJL-SOD1 g93A mice at mid-stage ALS (WT p<0.0001; mid-stage p=0.0028), with a noted trend towards improved muscle function even at later disease stages (p=0.064)[1].

DMSO: 60 mg/mL (260.56 mM), Sonication is recommended.

10% DMSO+40% PEG300+5% Tween 80+45% Saline: 1 mg/mL (4.34 mM), Sonication is recommended.