1005491-05-3
1005491-05-3 structure
- Name: Tirasemtiv
- Chemical Name: 5-ethynyl-3-pentan-3-yl-1H-imidazo[4,5-b]pyrazin-2-one
- CAS Number: 1005491-05-3
- Molecular Formula: C12H14N4O
- Molecular Weight: 230.266
- Catalog: Research Areas Neurological Disease
- Create Date: 2017-06-26 13:24:11
- Modify Date: 2024-01-02 18:50:03
-
Tirasemtiv is an activator of the fast skeletal muscle troponin complex.
| Name | 5-ethynyl-3-pentan-3-yl-1H-imidazo[4,5-b]pyrazin-2-one |
|---|---|
| Synonyms |
Tirasemtiv (USAN/INN)
6-Ethynyl-1-(3-pentanyl)-1,3-dihydro-2H-imidazo[4,5-b]pyrazin-2-one Tirasemtiv Tirasemtiv [INN] UNII-G8WSM7R635 1H-Imidazo[4,5-b]pyrazin-2-ol, 1-(1-ethylpropyl)-6-ethynyl- |
| Description | Tirasemtiv is an activator of the fast skeletal muscle troponin complex. |
|---|---|
| Related Catalog | |
| Target |
Troponin[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]. |
| Animal Admin | Mice[1] 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. |
| References |
| Density | 1.2±0.1 g/cm3 |
|---|---|
| Boiling Point | 422.3±55.0 °C at 760 mmHg |
| Molecular Formula | C12H14N4O |
| Molecular Weight | 230.266 |
| Flash Point | 209.2±31.5 °C |
| Exact Mass | 230.116760 |
| PSA | 63.57000 |
| LogP | 1.54 |
| Appearance | white solid |
| Vapour Pressure | 0.0±1.0 mmHg at 25°C |
| Index of Refraction | 1.620 |
| Storage condition | -20℃ |