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| Other names | CK-274 |
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| Formula | C18H19N5O2 |
| Molar mass | 337.383 g·mol−1 |
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Aficamten (CK-274) is a cardiac myosin inhibitor [1] developed by Cytokinetics for the treatment of obstructive hypertrophic cardiomyopathy. [2] [3] [4]
Hypertrophic cardiomyopathy is a condition in which muscle tissues of the heart become thickened without an obvious cause. The parts of the heart most commonly affected are the interventricular septum and the ventricles. This results in the heart being less able to pump blood effectively and also may cause electrical conduction problems.
MYH7 is a gene encoding a myosin heavy chain beta (MHC-β) isoform expressed primarily in the heart, but also in skeletal muscles. This isoform is distinct from the fast isoform of cardiac myosin heavy chain, MYH6, referred to as MHC-α. MHC-β is the major protein comprising the thick filament in cardiac muscle and plays a major role in cardiac muscle contraction.
Cardiomegaly is a medical condition in which the heart becomes enlarged. It is more commonly referred to simply as "having an enlarged heart". It is usually the result of underlying conditions that make the heart work harder, such as obesity, heart valve disease, high blood pressure (hypertension), and coronary artery disease. Cardiomyopathy is also associated with cardiomegaly.
Disopyramide is an antiarrhythmic medication used in the treatment of ventricular tachycardia. It is a sodium channel blocker and is classified as a Class 1a anti-arrhythmic agent. Disopyramide has a negative inotropic effect on the ventricular myocardium, significantly decreasing the contractility. Disopyramide also has an anticholinergic effect on the heart which accounts for many adverse side effects. Disopyramide is available in both oral and intravenous forms, and has a low degree of toxicity.
Septal myectomy is a cardiac surgery treatment for hypertrophic cardiomyopathy (HCM). The open-heart surgery entails removing a portion of the septum that is obstructing the flow of blood from the left ventricle to the aorta.
Cardiac muscle troponin T (cTnT) is a protein that in humans is encoded by the TNNT2 gene. Cardiac TnT is the tropomyosin-binding subunit of the troponin complex, which is located on the thin filament of striated muscles and regulates muscle contraction in response to alterations in intracellular calcium ion concentration.
Tropomyosin alpha-1 chain is a protein that in humans is encoded by the TPM1 gene. This gene is a member of the tropomyosin (Tm) family of highly conserved, widely distributed actin-binding proteins involved in the contractile system of striated and smooth muscles and the cytoskeleton of non-muscle cells.
A myosin light chain is a light chain of myosin. Myosin light chains were discovered by Chinese biochemist Cao Tianqin when he was a graduate student at the University of Cambridge in England.
The myosin-binding protein C, cardiac-type is a protein that in humans is encoded by the MYBPC3 gene. This isoform is expressed exclusively in heart muscle during human and mouse development, and is distinct from those expressed in slow skeletal muscle (MYBPC1) and fast skeletal muscle (MYBPC2).
Troponin C, also known as TN-C or TnC, is a protein that resides in the troponin complex on actin thin filaments of striated muscle and is responsible for binding calcium to activate muscle contraction. Troponin C is encoded by the TNNC1 gene in humans for both cardiac and slow skeletal muscle.
Myosin-10 also known as myosin heavy chain 10 or non-muscle myosin IIB (NM-IIB) is a protein that in humans is encoded by the MYH10 gene. Non-muscle myosins are expressed in a wide variety of tissues, but NM-IIB is the only non-muscle myosin II isoform expressed in cardiac muscle, where it localizes to adherens junctions within intercalated discs. NM-IIB is essential for normal development of cardiac muscle and for integrity of intercalated discs. Mutations in MYH10 have been identified in patients with left atrial enlargement.
Myosin regulatory light chain 2, ventricular/cardiac muscle isoform (MLC-2) also known as the regulatory light chain of myosin (RLC) is a protein that in humans is encoded by the MYL2 gene. This cardiac ventricular RLC isoform is distinct from that expressed in skeletal muscle (MYLPF), smooth muscle (MYL12B) and cardiac atrial muscle (MYL7).
Myosin heavy chain, α isoform (MHC-α) is a protein that in humans is encoded by the MYH6 gene. This isoform is distinct from the ventricular/slow myosin heavy chain isoform, MYH7, referred to as MHC-β. MHC-α isoform is expressed predominantly in human cardiac atria, exhibiting only minor expression in human cardiac ventricles. It is the major protein comprising the cardiac muscle thick filament, and functions in cardiac muscle contraction. Mutations in MYH6 have been associated with late-onset hypertrophic cardiomyopathy, atrial septal defects and sick sinus syndrome.
Myosin essential light chain (ELC), ventricular/cardiac isoform is a protein that in humans is encoded by the MYL3 gene. This cardiac ventricular/slow skeletal ELC isoform is distinct from that expressed in fast skeletal muscle (MYL1) and cardiac atrial muscle (MYL4). Ventricular ELC is part of the myosin molecule and is important in modulating cardiac muscle contraction.
Atrial Light Chain-1 (ALC-1), also known as Essential Light Chain, Atrial is a protein that in humans is encoded by the MYL4 gene. ALC-1 is expressed in fetal cardiac ventricular and fetal skeletal muscle, as well as fetal and adult cardiac atrial tissue. ALC-1 expression is reactivated in human ventricular myocardium in various cardiac muscle diseases, including hypertrophic cardiomyopathy, dilated cardiomyopathy, ischemic cardiomyopathy and congenital heart diseases.
Atrial Light Chain-2 (ALC-2) also known as Myosin regulatory light chain 2, atrial isoform (MLC2a) is a protein that in humans is encoded by the MYL7 gene. ALC-2 expression is restricted to cardiac muscle atria in healthy individuals, where it functions to modulate cardiac development and contractility. In human diseases, including hypertrophic cardiomyopathy, dilated cardiomyopathy, ischemic cardiomyopathy and others, ALC-2 expression is altered.
Omecamtiv mecarbil (INN), previously referred to as CK-1827452, is a cardiac-specific myosin activator. It is being studied for a potential role in the treatment of left ventricular systolic heart failure.
Myosin binding protein C, fast type is a protein that in humans is encoded by the MYBPC2 gene.
Cytokinetics, Inc. is a publicly traded biopharmaceutical company based in South San Francisco, California, that develops muscle activatorsand muscle inhibitors as potential treatments for people with diseases characterized by impaired or declining muscle function.
Mavacamten, sold under the brand name Camzyos, is a medication used to treat obstructive hypertrophic cardiomyopathy.