mavacamten   Click here for help

GtoPdb Ligand ID: 11265

Synonyms: Camzyos® | MYK-461 | MYK461
Approved drug PDB Ligand
mavacamten is an approved drug (FDA (2022), EMA (2023))
Compound class: Synthetic organic
Comment: Mavacamten (MYK-461) is an orally active myosin allosteric modulator [1] that was developed by MyoKardia as a novel treatment for obstructive hypertrophic cardiomyopathy (HCM). In 2020 MyoKardia was bought by Bristol Myers Squibb. The compound interacts with both α and β cardiac myosins in vitro. Preclinical pharmacokinetics are reported in [2]. Mavacamten attenuates hypertrophic and profibrotic gene expression in rodent models of HCM [1].
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 1
Hydrogen bond donors 2
Rotatable bonds 4
Topological polar surface area 66.89
Molecular weight 273.15
XLogP 3.79
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 C[C@@H](c1ccccc1)Nc1cc(=O)n(c(=O)[nH]1)C(C)C
Isomeric SMILES C[C@@H](c1ccccc1)Nc1cc(=O)n(c(=O)[nH]1)C(C)C
InChI InChI=1S/C15H19N3O2/c1-10(2)18-14(19)9-13(17-15(18)20)16-11(3)12-7-5-4-6-8-12/h4-11,16H,1-3H3,(H,17,20)/t11-/m0/s1
InChI Key RLCLASQCAPXVLM-NSHDSACASA-N
No information available.
Summary of Clinical Use Click here for help
Mavacamten (MYK-461) was progressed to Phase 3 clinical evaluation for obstructive hypertrophic cardiomyopathy (HCM). Full FDA approval was granted on April 30th 2022, as a treatment to alleviate symptoms and improve functional capacity in patients with symptomatic class II-III obstructive (per New York Heart Association assessment) hypertrophic cardiomyopathy. Bristol Myers Squibb are continuing to investigate mavacamten for other types of heart disease such as non-obstructive HCM and heart failure with preserved ejection fraction (HFpEF).
Mechanism Of Action and Pharmacodynamic Effects Click here for help
MYK-461 allosterically reduces the contractility of cardiac muscle by decreasing the ATPase activity of the cardiac myosin heavy chain that is found as a major component of sarcomeres.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT02842242 A Phase 2 Open-label Pilot Study Evaluating MYK-461 in Subjects With Symptomatic Hypertrophic Cardiomyopathy and Left Ventricular Outflow Tract Obstruction Phase 2 Interventional MyoKardia, Inc. 3
NCT02480296 Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Oral Doses of MYK-461 in Healthy Volunteers Phase 1 Interventional MyoKardia, Inc. 3
NCT03723655 A Long-Term Safety Extension Study of Mavacamten in Adults Who Have Completed MAVERICK-HCM or EXPLORER-HCM Phase 2/Phase 3 Interventional MyoKardia, Inc. 3
NCT04349072 A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive HCM Who Are Eligible for Septal Reduction Therapy Phase 3 Interventional MyoKardia, Inc. 3
NCT03470545 Clinical Study to Evaluate Mavacamten (MYK-461) in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy Phase 3 Interventional MyoKardia, Inc. Analysis of data collected from this study (the EXPLORER-HCM study) showed that mavacamten suppressed disease-specific symptoms and improved exercise capacity in patients with obstructive hypertrophic cardiomyopathy. 3-4