tirasemtiv   Click here for help

GtoPdb Ligand ID: 8280

Synonyms: CK-2017357
PDB Ligand
Compound class: Synthetic organic
Comment: Tirasemtiv acts as an activator of the fast skeletal muscle (type II) troponin complex [4]. The compound is being investigated as a potential treatment for diseases and conditions associated with aging, muscle weakness and wasting or neuromuscular dysfunction [4] (e.g. amyotrophic lateral sclerosis [5], myasthenia gravis and claudication [2]). In clinical trial tirasemtiv was not well tolerated, and this was likely a contributory factor to its lack of significant efficacy.
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 3
Hydrogen bond donors 1
Rotatable bonds 3
Topological polar surface area 63.57
Molecular weight 230.12
XLogP 1.74
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES CCC(n1c(=O)[nH]c2c1nc(C#C)cn2)CC
Isomeric SMILES CCC(n1c(=O)[nH]c2c1nc(C#C)cn2)CC
InChI 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)
InChI Key RSQGZEAXODVTOL-UHFFFAOYSA-N
References
1. Andrews JA, Cudkowicz ME, Hardiman O, Meng L, Bian A, Lee J, Wolff AA, Malik FI, Shefner JM. (2018)
VITALITY-ALS, a phase III trial of tirasemtiv, a selective fast skeletal muscle troponin activator, as a potential treatment for patients with amyotrophic lateral sclerosis: study design and baseline characteristics.
Amyotroph Lateral Scler Frontotemporal Degener, 19 (3-4): 259-266. [PMID:29402141]
2. Bauer TA, Wolff AA, Hirsch AT, Meng LL, Rogers K, Malik FI, Hiatt WR. (2014)
Effect of tirasemtiv, a selective activator of the fast skeletal muscle troponin complex, in patients with peripheral artery disease.
Vasc Med, 19 (4): 297-306. [PMID:24872402]
3. Hansen R, Saikali KG, Chou W, Russell AJ, Chen MM, Vijayakumar V, Stoltz RR, Baudry S, Enoka RM, Morgans DJ et al.. (2014)
Tirasemtiv amplifies skeletal muscle response to nerve activation in humans.
Muscle Nerve, 50 (6): 925-31. [PMID:24634285]
4. Russell AJ, Hartman JJ, Hinken AC, Muci AR, Kawas R, Driscoll L, Godinez G, Lee KH, Marquez D, Browne 4th WF et al.. (2012)
Activation of fast skeletal muscle troponin as a potential therapeutic approach for treating neuromuscular diseases.
Nat Med, 18 (3): 452-5. [PMID:22344294]
5. Scott A. (2017)
Drug therapy: On the treatment trail for ALS.
Nature, 550 (7676): S120-S121. [PMID:29045376]
6. Shefner JM, Cudkowicz ME, Hardiman O, Cockcroft BM, Lee JH, Malik FI, Meng L, Rudnicki SA, Wolff AA, Andrews JA et al.. (2019)
A phase III trial of tirasemtiv as a potential treatment for amyotrophic lateral sclerosis.
Amyotroph Lateral Scler Frontotemporal Degener, 0 (0): 1-11. [PMID:31081694]
7. Shefner JM, Watson ML, Meng L, Wolff AA, Neals/Cytokinetics STUDY Team. (2013)
A study to evaluate safety and tolerability of repeated doses of tirasemtiv in patients with amyotrophic lateral sclerosis.
Amyotroph Lateral Scler Frontotemporal Degener, 14 (7-8): 574-81. [PMID:23952636]