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].
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 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
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 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
References
1. Cleland JG, Teerlink JR, Senior R, Nifontov EM, Mc Murray JJ, Lang CC, Tsyrlin VA, Greenberg BH, Mayet J, Francis DP et al.. (2011)
The effects of the cardiac myosin activator, omecamtiv mecarbil, on cardiac function in systolic heart failure: a double-blind, placebo-controlled, crossover, dose-ranging phase 2 trial.
Lancet, 378 (9792): 676-83. [PMID:21856481]
2. Morgan BP, Muci A, Lu P-P, Kraynack EA, Tochimoto T, Morgans DJ Jr. (2009)
Compounds, compositions and methods.
Patent number: US7507735 B2. Assignee: Cytokinetics, Inc.. Priority date: 17/06/2004. Publication date: 24/03/2009.
3. Morgan BP, Muci A, Lu PP, Qian X, Tochimoto T, Smith WW, Garard M, Kraynack E, Collibee S, Suehiro I et al.. (2010)
Discovery of omecamtiv mecarbil the first, selective, small molecule activator of cardiac Myosin.
ACS Med Chem Lett, 1 (9): 472-7. [PMID:24900233]
4. Teerlink JR, Clarke CP, Saikali KG, Lee JH, Chen MM, Escandon RD, Elliott L, Bee R, Habibzadeh MR, Goldman JH et al.. (2011)
Dose-dependent augmentation of cardiac systolic function with the selective cardiac myosin activator, omecamtiv mecarbil: a first-in-man study.
Lancet, 378 (9792): 667-75. [PMID:21856480]
5. Teerlink JR, Diaz R, Felker GM, McMurray JJV, Metra M, Solomon SD, Adams KF, Anand I, Arias-Mendoza A, Biering-Sørensen T et al.. (2020)
Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction: GALACTIC-HF baseline characteristics and comparison with contemporary clinical trials.
Eur J Heart Fail, 22 (11): 2160-2171. [PMID:32985088]
6. Teerlink JR, Diaz R, Felker GM, McMurray JJV, Metra M, Solomon SD, Legg JC, Büchele G, Varin C, Kurtz CE et al.. (2020)
Omecamtiv Mecarbil in Chronic Heart Failure With Reduced Ejection Fraction: Rationale and Design of GALACTIC-HF.
JACC Heart Fail, 8 (4): 329-340. [PMID:32035892]