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.

tirasemtiv is commercially available from our sponsors

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 Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). 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

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
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.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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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

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
No information available.
Summary of Clinical Use Click here for help
Tirasemtiv has completed Phase 2 clinical trials for amyotrophic lateral sclerosis (ALS) [7] and intermittent claudication. A Phase 2 study in patients with myasthenia gravis was terminated. Tirasemtiv progressed to Phase 3 evaluation in ALS in the VITALITY-ALS study [6].
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Tirasemtiv sensitizes the sarcomere to calcium thus acting as a selective fast skeletal muscle troponin activator. Tirasemtiv slows the rate of calcium release from troponin C, thus prolonging muscular force production [4]. This action is reported to amplify the response of muscle to neuromuscular input [3], evidence that this type action could provide clinical benefit in diseases caused by diminished neuromuscular input.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT02496767 Ventilatory Investigation of Tirasemtiv and Assessment of Longitudinal Indices After Treatment for a Year Phase 3 Interventional Cytokinetics 1,6