Omecamtiv mecarbil

Omecamtiv mecarbil
Clinical data
Other names	CK-1827452
ATC code	C01CX10 (WHO) ;
Identifiers
	IUPAC name Methyl 4-[(2-fluoro-3-{[N-(6-methylpyridin-3-yl)carbamoyl]amino}phenyl)methyl]piperazine-1-carboxylate;
CAS Number	873697-71-3;
PubChem CID	11689883;
DrugBank	DB11816;
ChemSpider	9864610;
UNII	2M19539ERK;
KEGG	D09648;
ChEMBL	ChEMBL1800955;
PDB ligand	2OW (PDBe, RCSB PDB);
CompTox Dashboard (EPA)	DTXSID901025949 ;
Chemical and physical data
Formula	C20H24FN5O3
Molar mass	401.442 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES O=C(Nc1ccc(nc1)C)Nc2c(F)c(ccc2)CN3CCN(C(=O)OC)CC3;
	InChI InChI=1S/C20H24FN5O3/c1-14-6-7-16(12-22-14)23-19(27)24-17-5-3-4-15(18(17)21)13-25-8-10-26(11-9-25)20(28)29-2/h3-7,12H,8-11,13H2,1-2H3,(H2,23,24,27); Key:RFUBTTPMWSKEIW-UHFFFAOYSA-N;

Omecamtiv mecarbil (INN^[1]), previously referred to as CK-1827452, is a cardiac-specific myosin activator. It is an experimental drug being studied for a potential role in the treatment of left ventricular systolic heart failure.^[2]

Systolic heart failure involves a loss of effective actin-myosin cross bridges in the myocytes (heart muscle cells) of the left ventricle, which leads to a decreased ability of the heart to move blood through the body. This causes peripheral edema (blood pooling), which the sympathetic nervous system tries to correct^[3] by overstimulating the cardiac myocytes, leading to left ventricular hypertrophy, another characteristic of chronic heart failure.

inotropic therapies work by increasing the force of cardiac contraction, such as through calcium conduction or modulating adrenoreceptors. But these are limited by adverse events, including arrhythmias related to increased myocardial oxygen consumption, desensitization of adrenergic receptors, and altering intracellular calcium levels.^[4] Inotropes are also thought to be associated with worse prognosis.^[5]

^ World Health Organization (2010). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 64". WHO Drug Information. 24 (3). hdl:10665/74577.
^ Teerlink JR (December 2009). "A novel approach to improve cardiac performance: cardiac myosin activators". Heart Failure Reviews. 14 (4): 289–298. doi:10.1007/s10741-009-9135-0. PMC 2772957. PMID 19234787.
^ Dyke D, Koelling T (2008). "Heart failure due to left ventricular systolic dysfunction". In Eagle KA, Baliga RR (eds.). Practical Cardiology. Philadelphia: Lippincott Williams & Wilkins. pp. 246–285. ISBN 978-0-7817-7294-5.
^ Shen YT, Malik FI, Zhao X, Depre C, Dhar SK, Abarzúa P, et al. (July 2010). "Improvement of cardiac function by a cardiac Myosin activator in conscious dogs with systolic heart failure". Circulation: Heart Failure. 3 (4): 522–527. doi:10.1161/CIRCHEARTFAILURE.109.930321. PMID 20498236.
^ Nieminen M (March 2005). "Pharmacological options for acute heart failure syndromes: current treatments and unmet needs". Eur Heart J. 7: B20-4. doi:10.1093/eurheartj/sui009.

[1] World Health Organization (2010). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 64". WHO Drug Information. 24 (3). hdl:10665/74577.

[Teerlink2009-2] Teerlink JR (December 2009). "A novel approach to improve cardiac performance: cardiac myosin activators". Heart Failure Reviews. 14 (4): 289–298. doi:10.1007/s10741-009-9135-0. PMC 2772957. PMID 19234787.

[DykeKoelling-3] Dyke D, Koelling T (2008). "Heart failure due to left ventricular systolic dysfunction". In Eagle KA, Baliga RR (eds.). Practical Cardiology. Philadelphia: Lippincott Williams & Wilkins. pp. 246–285. ISBN 978-0-7817-7294-5.

[Shen2010-4] Shen YT, Malik FI, Zhao X, Depre C, Dhar SK, Abarzúa P, et al. (July 2010). "Improvement of cardiac function by a cardiac Myosin activator in conscious dogs with systolic heart failure". Circulation: Heart Failure. 3 (4): 522–527. doi:10.1161/CIRCHEARTFAILURE.109.930321. PMID 20498236.

[Nieminen-5] Nieminen M (March 2005). "Pharmacological options for acute heart failure syndromes: current treatments and unmet needs". Eur Heart J. 7: B20-4. doi:10.1093/eurheartj/sui009.

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