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# Cardiac myosin inhibitors

Oral drugs that calm an overactive heart muscle by limiting myosin-actin cross-bridges. Used in obstructive hypertrophic cardiomyopathy.

Updated Nov 1, 2026

## What they are

A new class aimed at the cause of hypertrophic cardiomyopathy (HCM): too many myosin heads working at once. Mavacamten was first; aficamten followed.

## Mechanism of action

Cardiac (β) myosin is the motor protein that pulls on actin to make the heart contract. In HCM, sarcomere mutations leave too many myosin heads 'on' and too few in an energy-saving, super-relaxed state. Cardiac myosin inhibitors bind myosin allosterically and reversibly, reduce the number of heads that can bind actin and shift myosin towards the super-relaxed state: contractility falls, the outflow-tract obstruction eases and relaxation improves.

Target: Cardiac β-myosin heavy chain (MYH7), motor domain

## Key points

- Treat the mechanism of HCM (hypercontractility) rather than just the symptoms.
- Main risk: too much negative inotropy, i.e. systolic heart failure; ejection fraction is followed by echocardiography.
- Available only through restricted (REMS-type) programmes because of the heart failure risk.
- Many drug interactions through CYP enzymes (mavacamten: CYP2C19 and CYP3A4).
- May harm the fetus; mavacamten also makes hormonal contraceptives less reliable.

## Drugs in this class

- [**Mavacamten** The first cardiac myosin inhibitor: an oral drug that reduces excess heart contraction in symptomatic obstructive… Cardiac β-myosin (MYH7), motor domain ATPase](https://durgical.com/en/pharmacology/mavacamten/)

## Others in the class

- aficamten

## Test yourself

Think of the answer, then tap the question to see it.

## What is the molecular problem in HCM that cardiac myosin inhibitors correct?

Too many myosin heads are active (hypercontractility) and too few are in the super-relaxed state; the drugs reduce active cross-bridges.

## Why is echocardiography repeated during treatment?

To detect a fall in ejection fraction, because the drugs can cause systolic heart failure.

## Which type of HCM are these drugs approved for?

Symptomatic obstructive HCM.

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: [Mavacamten: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a622047.html) (MedlinePlus (U.S. National Library of Medicine), 2022); [Aficamten: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a626021.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [Cryo-EM structure of human beta-cardiac myosin bound to mavacamten in the interacting-heads motif and S2-FH docked state](https://www.rcsb.org/structure/9YP9) (RCSB Protein Data Bank, 2026).

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/classes/cardiac-myosin-inhibitors/