aficamten   Click here for help

GtoPdb Ligand ID: 11524

Synonyms: CK-274 | CK-3773274 | CK3773274
PDB Ligand
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 [1-3,6]. 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.

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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 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

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 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

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/)
References
1. Alsulami K, Marston S. (2020)
Small Molecules acting on Myofilaments as Treatments for Heart and Skeletal Muscle Diseases.
Int J Mol Sci, 21 (24). [PMID:33339418]
2. Argirò A, Zampieri M, Berteotti M, Marchi A, Tassetti L, Zocchi C, Iannone L, Bacchi B, Cappelli F, Stefàno P et al.. (2021)
Emerging Medical Treatment for Hypertrophic Cardiomyopathy.
J Clin Med, 10 (5). [PMID:33804412]
3. Chuang C, Collibee S, Ashcraft L, Wang W, Vander Wal M, Wang X, Hwee DT, Wu Y, Wang J, Chin ER et al.. (2021)
Discovery of Aficamten (CK-274), a Next-Generation Cardiac Myosin Inhibitor for the Treatment of Hypertrophic Cardiomyopathy.
J Med Chem, 64 (19): 14142-14152. [PMID:34606259]
4. Coats CJ, Maron MS, Abraham TP, Olivotto I, Lee MMY, Arad M, Cardim N, Ma CS, Choudhury L, Düngen HD et al.. (2024)
Exercise Capacity in Patients With Obstructive Hypertrophic Cardiomyopathy: SEQUOIA-HCM Baseline Characteristics and Study Design.
JACC Heart Fail, 12 (1): 199-215. [PMID:38032573]
5. Maron MS, Masri A, Nassif ME, Barriales-Villa R, Arad M, Cardim N, Choudhury L, Claggett B, Coats CJ, Düngen HD et al.. (2024)
Aficamten for Symptomatic Obstructive Hypertrophic Cardiomyopathy.
NEJM,. DOI: 10.1056/NEJMoa2401424
6. Mehra N, Ali AH, Desai MY. (2023)
Obstructive hypertrophic cardiomyopathy: a review of new therapies.
Future Cardiol, 19 (13): 661-670. [PMID:37933625]
7. Owens AT, Masri A, Abraham TP, Choudhury L, Rader F, Symanski JD, Turer AT, Wong TC, Tower-Rader A, Coats CJ et al.. (2023)
Aficamten for Drug-Refractory Severe Obstructive Hypertrophic Cardiomyopathy in Patients Receiving Disopyramide: REDWOOD-HCM Cohort 3.
J Card Fail, 29 (11): 1576-1582. [PMID:37473912]
8. Sebastian SA, Padda I, Lehr EJ, Johal G. (2023)
Aficamten: A Breakthrough Therapy for Symptomatic Obstructive Hypertrophic Cardiomyopathy.
Am J Cardiovasc Drugs, 23 (5): 519-532. [PMID:37526885]