| CAS |
No.1005491-05-3 |
| 英文名称 |
Tirasemtiv |
| 别名 |
;CK-2017357;第九醇; |
| 分子式 |
C12H14N4O |
| 分子量 |
230.27 |
| 溶解性 |
Soluble in DMSO |
| 纯度 |
≥98% |
| 外观(性状) |
White to off-white Solid |
| 储存条件 |
Powder:-20℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| MDL |
MFCD28023588 |
| SMILES |
CCC(CC)N1C2=NC(=CN=C2NC1=O)C#C |
| 靶点 |
Others |
| 通路 |
Others |
| 背景说明 |
是一种新型的快速骨骼肌钙蛋白小分子激活剂。 |
| 生物活性 |
Tirasemtiv is an activator of the fast skeletal muscle troponin complex.[1] |
| In Vitro |
Tirasemtiv is a fast skeletal troponin activator that sensitizes the sarcomere to calcium; this mechanism of action amplifies the response of muscle to neuromuscular input producing greater force when nerve input is reduced. Tirasemtiv selectively sensitizes fast skeletal muscle troponin to calcium(Ca2+)，and slows the rate of Ca2+ release from the regulatory troponin complex of fast skeletal muscle[1]. |
| 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]. |
| 动物实验 |
Wild-type background strain B6SJLF1/J mice and B6SJL-SOD1G93A mice over-expressing the human SOD-1 gene with mutation G93A are group-housed in a 12-hour light cycle and fed standard chow and water ad libitum. Tirasemtiv is administered in solution(50% PEG300/10% EtOH/40% Cavitron cyclodextrin formulation)as a single slow bolus over a 2 minute period via a catheter in the contralateral femoral artery placed above the aortic bifurcation. Tirasemtiv bolus injections(2，2，2，and 4 mg/kg)are given at approximately 20 min intervals to achieve a cumulative dose of 10 mg/kg in order to assess the dose response，with a maximal dosage volume of 5 mL/kg. At the end of each experiment，a single terminal blood sample is drawn via cardiac puncture for compound concentration analysis.[1] |
| 数据来源文献 |
[1]. Hwee DT， et al. Fast skeletal muscle troponin activator tirasemtiv increases muscle function and performance in the B6SJL-SOD1G93A ALS mouse model. PLoS One. 2014 May 7;9(5):e96921. |
| 规格 |
1mg 5mg 10mg |
| 单位 |
瓶 |
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