Details
| 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=C1N=C(C=N2)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)
DescriptionCurator's Comment: Description was created using several sources including:
http://www.als.net/news/pivotal-study-for-tirasemtiv-opens-for-enrollment/
Curator's Comment: Description was created using several sources including:
http://www.als.net/news/pivotal-study-for-tirasemtiv-opens-for-enrollment/
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.
Approval Year
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
11.271 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22591195 |
500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered: |
TIRASEMTIV plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
18.3 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24872402 |
750 mg single, oral dose: 750 mg route of administration: Oral experiment type: SINGLE co-administered: |
TIRASEMTIV plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
175.881 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22591195 |
500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered: |
TIRASEMTIV plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
238.2 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24872402 |
750 mg single, oral dose: 750 mg route of administration: Oral experiment type: SINGLE co-administered: |
TIRASEMTIV plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Doses
| Dose | Population | Adverse events |
|---|---|---|
750 mg single, oral Highest studied dose |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
Disc. AE: Dizziness... AEs leading to discontinuation/dose reduction: Dizziness (grade 3, 6%) Sources: |
250 mg 2 times / day multiple, oral Studied dose Dose: 250 mg, 2 times / day Route: oral Route: multiple Dose: 250 mg, 2 times / day Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
Disc. AE: Ataxia, Confusion... AEs leading to discontinuation/dose reduction: Ataxia (6.25%) Sources: Confusion (6.25%) |
250 mg 2 times / day multiple, oral Studied dose Dose: 250 mg, 2 times / day Route: oral Route: multiple Dose: 250 mg, 2 times / day Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
Disc. AE: Dizziness, Fatigue... AEs leading to discontinuation/dose reduction: Dizziness (10.3%) Sources: Fatigue (7.4%) Nausea (4.2%) |
375 mg 1 times / day multiple, oral Studied dose Dose: 375 mg, 1 times / day Route: oral Route: multiple Dose: 375 mg, 1 times / day Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
Disc. AE: Dizziness, Mental status changes... AEs leading to discontinuation/dose reduction: Dizziness (5.6%) Sources: Mental status changes (5.6%) |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Dizziness | grade 3, 6% Disc. AE |
750 mg single, oral Highest studied dose |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Ataxia | 6.25% Disc. AE |
250 mg 2 times / day multiple, oral Studied dose Dose: 250 mg, 2 times / day Route: oral Route: multiple Dose: 250 mg, 2 times / day Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Confusion | 6.25% Disc. AE |
250 mg 2 times / day multiple, oral Studied dose Dose: 250 mg, 2 times / day Route: oral Route: multiple Dose: 250 mg, 2 times / day Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Dizziness | 10.3% Disc. AE |
250 mg 2 times / day multiple, oral Studied dose Dose: 250 mg, 2 times / day Route: oral Route: multiple Dose: 250 mg, 2 times / day Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Nausea | 4.2% Disc. AE |
250 mg 2 times / day multiple, oral Studied dose Dose: 250 mg, 2 times / day Route: oral Route: multiple Dose: 250 mg, 2 times / day Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Fatigue | 7.4% Disc. AE |
250 mg 2 times / day multiple, oral Studied dose Dose: 250 mg, 2 times / day Route: oral Route: multiple Dose: 250 mg, 2 times / day Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Dizziness | 5.6% Disc. AE |
375 mg 1 times / day multiple, oral Studied dose Dose: 375 mg, 1 times / day Route: oral Route: multiple Dose: 375 mg, 1 times / day Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Mental status changes | 5.6% Disc. AE |
375 mg 1 times / day multiple, oral Studied dose Dose: 375 mg, 1 times / day Route: oral Route: multiple Dose: 375 mg, 1 times / day Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Tirasemtiv amplifies skeletal muscle response to nerve activation in humans. | 2014-12 |
|
| Effect of tirasemtiv, a selective activator of the fast skeletal muscle troponin complex, in patients with peripheral artery disease. | 2014-08 |
|
| A study to evaluate safety and tolerability of repeated doses of tirasemtiv in patients with amyotrophic lateral sclerosis. | 2013-12 |
|
| Activation of fast skeletal muscle troponin as a potential therapeutic approach for treating neuromuscular diseases. | 2012-02-19 |
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.
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| Classification Tree | Code System | Code | ||
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FDA ORPHAN DRUG |
301710
Created by
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EU-Orphan Drug |
EU/3/12/970
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NCI_THESAURUS |
C78272
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CHEMBL3039529
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23729157
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G8WSM7R635
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C152657
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DTXSID90143379
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DB12209
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1005491-05-3
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ACTIVE MOIETY
