| Identification | Back Directory | [Name]
tiraseMtiv (CK-2017357) | [CAS]
1005491-05-3 | [Synonyms]
CS-1484
TiraseMtiv
CK 2017357
Tirasemitiv
Tirasemtiv, >=98%
tiraseMtiv (CK-2017357)
Tirasemtiv(CK-2017357), >98%
CK-2017357; CK2017357; CK 2017357
5-ethynyl-3-pentan-3-yl-1H-imidazo[4,5-b]pyrazin-2-one
6-ethynyl-1-(pentan-3-yl)-1H-iMidazo[4,5-b]pyrazin-2-ol
6-ETHYNYL-1-(PENTAN-3-YL)-1H-IMIDAZO[4,5-B]PYRAZIN-2(3H)-ONE
1-(1-Ethylpropyl)-6-ethynyl-1,3-dihydro-2H-imidazo[4,5-b]pyrazin-2-one
2H-Imidazo[4,5-b]pyrazin-2-one, 1-(1-ethylpropyl)-6-ethynyl-1,3-dihydro-
Tirasemtiv 1-(1-Ethylpropyl)-6-ethynyl-1,3-dihydro-2H-imidazo[4,5-b]pyrazin-2-one | [Molecular Formula]
C12H14N4O | [MDL Number]
MFCD27978476 | [MOL File]
1005491-05-3.mol | [Molecular Weight]
230.27 |
| Chemical Properties | Back Directory | [Melting point ]
>130°C (dec.) | [storage temp. ]
-20°C Freezer | [solubility ]
DMSO (Slightly), Methanol (Slightly) | [form ]
Solid | [color ]
Beige to Brown |
| Hazard Information | Back Directory | [Description]
Tirasemtiv is an activator of the fast skeletal troponin complex.1 It selectively binds to purified fast skeletal troponin complex (Kd = 40 nM) over slow skeletal (Kd = 3,800 nM) and cardiac troponin complexes. Tirasemtiv (20 μM) slows the rate of calcium release from the fast skeletal troponin complex. It increases the ATPase activity of isolated rabbit fast skeletal myofibrils at a fixed calcium concentration (EC50 = 390 nM) and sensitizes skinned fast skeletal muscle fibers isolated from human and rabbit to calcium in a concentration-dependent manner. Tirasemtiv increases in situ extensor digitorum longus (EDL) muscle force and forelimb grip strength in a rat model of myasthenia gravis. It also increases forelimb grip strength, grid hang test performance, and rotarod performance in a mouse model of amyotrophic lateral sclerosis (ALS) when administered at a dose of 10 mg/kg.2 | [Uses]
Tirasemtiv is a fast skeletal muscle troponin activator and is used for treating patients with amyotrophic lateral sclerosis (ALS). | [in vivo]
A single dose of Tirasemtiv significantly increases submaximal isometric force, forelimb grip strength, grid hang time, and rotarod performance in a female transgenic mouse model (B6SJL-SOD1G93A) of ALS with functional deficits. Additionally, diaphragm force and tidal volume are significantly higher in Tirasemtiv-treated female B6SJL-SOD1G93A mice. At the 25% deficit milestone, vehicle-treated B6SJL-SOD1G93A mice demonstrated forelimb grip strength of 49.6±4.6 g. Tirasemtiv increases grip strength by 38% to 68.6±8.1g (p<0.05, single tailed t-test). Tirasemtiv doses of 2, 2, 2, and 4 mg/kg given at approximately 20 min intervals to achieve a cumulative dose of 10 mg/kg. Regression analysis of the log dose vs. response relationship indicated that Tirasemtiv significantly increased muscle force in WT and mid-stage B6SJL-SOD1G93A mice (WT p<0.0001; mid-stage p=0.0028). At later stages of disease, the mice exhibited a trend for increased muscle function in response to Tirasemtivcompared to baseline (p=0.064)[1]. | [References]
[1] ALAN J RUSSELL. Activation of fast skeletal muscle troponin as a potential therapeutic approach for treating neuromuscular diseases[J]. Nature Medicine, 2012, 18 3: 452-455. DOI: 10.1038/nm.2618
[2] DARREN T HWEE. Fast skeletal muscle troponin activator tirasemtiv increases muscle function and performance in the B6SJL-SOD1G93A ALS mouse model.[J]. PLoS ONE, 2014: e96921. DOI: 10.1371/journal.pone.0096921 |
|
|