aficamten   Click here for help

GtoPdb Ligand ID: 11524

Synonyms: CK-274 | CK-3773274 | CK3773274
Compound class: Synthetic organic
Comment: Aficamten (CK-3773274) is an orally administered cardiac myosin inhibitor that was developed by Cytokinetics as a potential treatment for hypertrophic cardiomyopathies [1-3]. It was designed to reduce the hypercontractility of cardiac sarcomeres that is thought to drive hypertrophy and fibrosis in heart muscle, by binding directly to a distinct and selective allosteric binding site on cardiac myosin.
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 4
Hydrogen bond donors 1
Rotatable bonds 5
Topological polar surface area 85.84
Molecular weight 337.15
XLogP 2.56
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 CCc1onc(n1)c1ccc2c(c1)CC[C@H]2NC(=O)c1cnn(c1)C
Isomeric SMILES CCc1onc(n1)c1ccc2c(c1)CC[C@H]2NC(=O)c1cnn(c1)C
InChI InChI=1S/C18H19N5O2/c1-3-16-21-17(22-25-16)12-4-6-14-11(8-12)5-7-15(14)20-18(24)13-9-19-23(2)10-13/h4,6,8-10,15H,3,5,7H2,1-2H3,(H,20,24)/t15-/m1/s1
InChI Key IOVAZWDIRCRMTM-OAHLLOKOSA-N
No information available.
Summary of Clinical Use Click here for help
CK-3773274 has been advanced to clinical evaluation in patients with obstructive hypertrophic cardiomyopathy (HCM). The compound was granted FDA orphan drug status in early 2021 for the treatment of symptomatic HCM.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT04848506 CY 6022 is an Open Label Study to Collect Long-term Safety and Tolerability Data for CK-3773274 Phase 2 Interventional Cytokinetics
NCT04219826 REDWOOD-HCM: Randomized Evaluation of Dosing With CK-3773274 in Obstructive Outflow Disease in HCM Phase 2 Interventional Cytokinetics
NCT03767855 A Single and Multiple Ascending Dose Study of CK-3773274 in Healthy Adult Subjects Phase 1 Interventional Cytokinetics