| Stereochemistry | ACHIRAL |
| Molecular Formula | C12H14N4O |
| Molecular Weight | 230.2658 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CCC(CC)N1C(=O)NC2=NC=C(N=C12)C#C
InChI
InChIKey=RSQGZEAXODVTOL-UHFFFAOYSA-N
InChI=1S/C12H14N4O/c1-4-8-7-13-10-11(14-8)16(12(17)15-10)9(5-2)6-3/h1,7,9H,5-6H2,2-3H3,(H,13,15,17)
Tirasemtiv is a fast skeletal troponin activator and is a candidate amyotrophic lateral sclerosis (AML) therapeutic. It is a small molecule that enhances the signals between motor neurons and neuromuscular junctions. Tirasemtiv increases muscle strength by amplifying the response of muscle when neuromuscular input is diminished secondary to a neuromuscular disease. Tirasemtiv selectively binds to the fast skeletal troponin complex, thus slowing down the rate of calcium release from troponin C and sensitizing muscle to calcium. As a consequence, the force-calcium relationship of muscle fibers shifts leftwards as does the force-frequency relationship of a nerve-muscle pair.
Originator
Approval Year
Doses
AEs
Sourcing
Sample Use Guides
Day 1 through week 48 - 125 mg of tirasemtiv twice a day (Experimental Group 2); day 1 through week 2 - 125 mg of tirasemtiv twice a day, weeks 3 through 48 - 125 mg in AM and 250 mg in PM (Experimental Group 3) and weeks 3 and 4 - 125 mg in AM and 250 mg in PM. weeks 5 through 48 - 500 mg in AM and 500 mg in PM.
Route of Administration:
Oral
Addition of 5.0 uM CK-2017357 (tirasemtiv) to fast skeletal myofibrils resulted in a leftward shift in the calcium-dependent myosin adenosine triphosphatase (ATPase) relationship with the pCa50 shifting from 5.61 ± 0.01 (control) to 6.52 ± 0.02 (CK-2017357, 5.0 uM). An increase in the ATPase rate at a fixed calcium concentration resulted in CK-2017357 EC50 of 390 ± 17 nM for fast skeletal muscle, with little or no effect in myofibrils from slow skeletal and cardiac muscle demonstrating that CK-2017357 is a selective calcium sensitizer of the fast skeletal troponin complex.
ACTIVE MOIETY
