omecamtiv mecarbil   Click here for help

GtoPdb Ligand ID: 8740

Synonyms: AMG 423 | AMG-423 | CK-1827452
PDB Ligand
Compound class: Synthetic organic
Comment: Omecamtiv mecarbil is an investigational small molecule which is a direct activator of cardiac myosin [3]. This compound is being investigated as a novel therapy for patients with chronic heart failure due to systolic dysfunction. Results from the first-in-man study are reported by Teerlink et al. (2011) [4].
Omecamtiv mecarbil is claimed in patent US7507735 B2 [2].

omecamtiv mecarbil 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 8
Hydrogen bond donors 2
Rotatable bonds 8
Topological polar surface area 86.8
Molecular weight 401.19
XLogP 1.06
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 COC(=O)N1CCN(CC1)Cc1cccc(c1F)NC(=O)Nc1ccc(nc1)C
Isomeric SMILES COC(=O)N1CCN(CC1)Cc1cccc(c1F)NC(=O)Nc1ccc(nc1)C
InChI InChI=1S/C20H24FN5O3/c1-14-6-7-16(12-22-14)23-19(27)24-17-5-3-4-15(18(17)21)13-25-8-10-26(11-9-25)20(28)29-2/h3-7,12H,8-11,13H2,1-2H3,(H2,23,24,27)
InChI Key RFUBTTPMWSKEIW-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
Omecamtiv mecarbil is being evaluated in clinical trials as a therapy for heart failure [1,6].
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Direct activation of cardiac myosin improves cardiac contractility without changing the calcium transient, as occurs with current inotropic therapies used improve cardiac function in congestive heart failure. The myosin present in the heart is a type II myosin and is a major component of sarcomeres, the basic units of cardiac muscle contraction. The MYH6 and MYH7 genes encode myosin heavy chain proteins which are expressed in the heart.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT02929329 Registrational Study With Omecamtiv Mecarbil/AMG 423 to Treat Chronic Heart Failure With Reduced Ejection Fraction Phase 3 Interventional Amgen Galactic-HF trial: Despite being better than placebo in preventing hospitalisations and other interventions in patients with heart failure with reduced ejection fraction (HFrEF), omecamtiv mecarbil did not extend patients' lives. 5