Omecamtiv mecarbil
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MedKoo CAT#: 510321

CAS#: 873697-71-3(free base)

Description: Omecamtiv mecarbil, also known as CK-1827452, is a cardiac specific myosin activator. It is clinically tested for its role in the treatment of left ventricular systolic heart failure. Omecamtiv Mecarbil specifically targets and activates myocardial ATPase and improves energy utilization. Omecamtiv Mecarbil improves systolic function by increasing the systolic ejection duration/stroke volume, without consuming more ATP energy, oxygen or altering intracellular calcium levels causing an overall improvement in cardiac efficiency. (source: http://en.wikipedia.org/wiki/Omecamtiv_mecarbil)


Chemical Structure

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Omecamtiv mecarbil
CAS# 873697-71-3(free base)

Theoretical Analysis

MedKoo Cat#: 510321
Name: Omecamtiv mecarbil
CAS#: 873697-71-3(free base)
Chemical Formula: C20H24FN5O3
Exact Mass: 401.19
Molecular Weight: 401.442
Elemental Analysis: C, 59.84; H, 6.03; F, 4.73; N, 17.45; O, 11.96

Price and Availability

Size Price Availability Quantity
10mg USD 150
25mg USD 250
50mg USD 450
100mg USD 750
200mg USD 1250
500mg USD 2050
1g USD 3450
2g USD 5250
5g USD 8650
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Related CAS #: 1628699-20-6 (2HCl H2O)   873697-71-3(free base)  

Synonym: Omecamtiv mecarbil; CK1827452; CK 1827452; CK1827452.

IUPAC/Chemical Name: methyl 4-(2-fluoro-3-(3-(6-methylpyridin-3-yl)ureido)benzyl)piperazine-1-carboxylate

InChi Key: RFUBTTPMWSKEIW-UHFFFAOYSA-N

InChi Code: 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)

SMILES Code: O=C(N1CCN(CC2=CC=CC(NC(NC3=CC=C(C)N=C3)=O)=C2F)CC1)OC

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:         

Product Data:
Biological target: Omecamtiv mecarbil (CK-1827452) is a selective cardiac myosin activator.
In vitro activity: OM (omecamtiv mecarbil) can reduce the actin sliding velocity more than 100-fold in the in vitro motility assay. The ionic strength dependence of in vitro motility suggests the inhibition may be at least partially due to drag forces from weakly attached myosin heads. OM causes an increase in duty ratio examined in the motility assay. Experiments with permeabilized human myocardium demonstrate that OM increases calcium sensitivity and slows force development (ktr) in a concentration-dependent manner, whereas the maximally activated force is unchanged. Reference: J Biol Chem. 2017 Mar 3;292(9):3768-3778. https://pubmed.ncbi.nlm.nih.gov/28082673/
In vivo activity: Omecamtiv mecarbil increased systolic function in sHF dogs, chronically instrumented to measure LV pressure, wall thickness, and cardiac output. Omecamtiv mecarbil, infused for 24 hours, induced a sustained increase without desensitization (P<0.05) in wall thickening (25+/-6.2%), stroke volume (44+/-6.5%) and cardiac output (22+/-2.8%), and decreased heart rate (15+/-3.0%). Reference: Circ Heart Fail. 2010 Jul;3(4):522-7. https://pubmed.ncbi.nlm.nih.gov/20498236/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMF 30.0 74.73
DMF:PBS (pH 7.2) (1:2) 0.3 0.82
DMSO 36.7 91.34
Ethanol 5.5 13.70

Preparing Stock Solutions

The following data is based on the product molecular weight 401.44 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Swenson AM, Tang W, Blair CA, Fetrow CM, Unrath WC, Previs MJ, Campbell KS, Yengo CM. Omecamtiv Mecarbil Enhances the Duty Ratio of Human β-Cardiac Myosin Resulting in Increased Calcium Sensitivity and Slowed Force Development in Cardiac Muscle. J Biol Chem. 2017 Mar 3;292(9):3768-3778. doi: 10.1074/jbc.M116.748780. Epub 2017 Jan 12. PMID: 28082673; PMCID: PMC5339759. 2. Morgan BP, Muci A, Lu PP, Qian X, Tochimoto T, Smith WW, Garard M, Kraynack E, Collibee S, Suehiro I, Tomasi A, Valdez SC, Wang W, Jiang H, Hartman J, Rodriguez HM, Kawas R, Sylvester S, Elias KA, Godinez G, Lee K, Anderson R, Sueoka S, Xu D, Wang Z, Djordjevic N, Malik FI, Morgans DJ Jr. Discovery of omecamtiv mecarbil the first, selective, small molecule activator of cardiac Myosin. ACS Med Chem Lett. 2010 Aug 20;1(9):472-7. doi: 10.1021/ml100138q. PMID: 24900233; PMCID: PMC4007828. 3. Mamidi R, Gresham KS, Li A, dos Remedios CG, Stelzer JE. Molecular effects of the myosin activator omecamtiv mecarbil on contractile properties of skinned myocardium lacking cardiac myosin binding protein-C. J Mol Cell Cardiol. 2015 Aug;85:262-72. doi: 10.1016/j.yjmcc.2015.06.011. Epub 2015 Jun 20. PMID: 26100051; PMCID: PMC4667802. 4. Shen YT, Malik FI, Zhao X, Depre C, Dhar SK, Abarzúa P, Morgans DJ, Vatner SF. Improvement of cardiac function by a cardiac Myosin activator in conscious dogs with systolic heart failure. Circ Heart Fail. 2010 Jul;3(4):522-7. doi: 10.1161/CIRCHEARTFAILURE.109.930321. Epub 2010 May 24. PMID: 20498236.
In vitro protocol: 1. Swenson AM, Tang W, Blair CA, Fetrow CM, Unrath WC, Previs MJ, Campbell KS, Yengo CM. Omecamtiv Mecarbil Enhances the Duty Ratio of Human β-Cardiac Myosin Resulting in Increased Calcium Sensitivity and Slowed Force Development in Cardiac Muscle. J Biol Chem. 2017 Mar 3;292(9):3768-3778. doi: 10.1074/jbc.M116.748780. Epub 2017 Jan 12. PMID: 28082673; PMCID: PMC5339759. 2. Morgan BP, Muci A, Lu PP, Qian X, Tochimoto T, Smith WW, Garard M, Kraynack E, Collibee S, Suehiro I, Tomasi A, Valdez SC, Wang W, Jiang H, Hartman J, Rodriguez HM, Kawas R, Sylvester S, Elias KA, Godinez G, Lee K, Anderson R, Sueoka S, Xu D, Wang Z, Djordjevic N, Malik FI, Morgans DJ Jr. Discovery of omecamtiv mecarbil the first, selective, small molecule activator of cardiac Myosin. ACS Med Chem Lett. 2010 Aug 20;1(9):472-7. doi: 10.1021/ml100138q. PMID: 24900233; PMCID: PMC4007828.
In vivo protocol: 1. Mamidi R, Gresham KS, Li A, dos Remedios CG, Stelzer JE. Molecular effects of the myosin activator omecamtiv mecarbil on contractile properties of skinned myocardium lacking cardiac myosin binding protein-C. J Mol Cell Cardiol. 2015 Aug;85:262-72. doi: 10.1016/j.yjmcc.2015.06.011. Epub 2015 Jun 20. PMID: 26100051; PMCID: PMC4667802. 2. Shen YT, Malik FI, Zhao X, Depre C, Dhar SK, Abarzúa P, Morgans DJ, Vatner SF. Improvement of cardiac function by a cardiac Myosin activator in conscious dogs with systolic heart failure. Circ Heart Fail. 2010 Jul;3(4):522-7. doi: 10.1161/CIRCHEARTFAILURE.109.930321. Epub 2010 May 24. PMID: 20498236.

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 1: Spinarova L, Spinar J. Pharmacotherapy of dilated cardiomyopathy. Curr Pharm Des. 2014;21(4):449-58. PubMed PMID: 25483945.

2: Greenberg BH, Chou W, Saikali KG, Escandón R, Lee JH, Chen MM, Treshkur T, Megreladze I, Wasserman SM, Eisenberg P, Malik FI, Wolff AA, Shaburishvili T. Safety and Tolerability of Omecamtiv Mecarbil During Exercise in Patients With Ischemic Cardiomyopathy and Angina. JACC Heart Fail. 2014 Nov 11. pii: S2213-1779(14)00379-5. doi: 10.1016/j.jchf.2014.07.009. [Epub ahead of print] PubMed PMID: 25453536.

3: McNeice AH, McAleavey NM, Menown IB. Advances in clinical cardiology. Adv Ther. 2014 Aug;31(8):837-60. doi: 10.1007/s12325-014-0141-9. Epub 2014 Jul 30. PubMed PMID: 25074280.

4: Wang Y, Ajtai K, Burghardt TP. Analytical comparison of natural and pharmaceutical ventricular myosin activators. Biochemistry. 2014 Aug 19;53(32):5298-306. doi: 10.1021/bi500730t. Epub 2014 Aug 7. PubMed PMID: 25068717; PubMed Central PMCID: PMC4139156.

5: Tarone G, Balligand JL, Bauersachs J, Clerk A, De Windt L, Heymans S, Hilfiker-Kleiner D, Hirsch E, Iaccarino G, Knöll R, Leite-Moreira AF, Lourenço AP, Mayr M, Thum T, Tocchetti CG. Targeting myocardial remodelling to develop novel therapies for heart failure: a position paper from the Working Group on Myocardial Function of the European Society of Cardiology. Eur J Heart Fail. 2014 May;16(5):494-508. doi: 10.1002/ejhf.62. Epub 2014 Mar 17. PubMed PMID: 24639064.

6: Shintani SA, Oyama K, Kobirumaki-Shimozawa F, Ohki T, Ishiwata S, Fukuda N. Sarcomere length nanometry in rat neonatal cardiomyocytes expressed with α-actinin-AcGFP in Z discs. J Gen Physiol. 2014 Apr;143(4):513-24. doi: 10.1085/jgp.201311118. Epub 2014 Mar 17. PubMed PMID: 24638993; PubMed Central PMCID: PMC3971663.

7: Valentova M, von Haehling S. An overview of recent developments in the treatment of heart failure: update from the ESC Congress 2013. Expert Opin Investig Drugs. 2014 Apr;23(4):573-8. doi: 10.1517/13543784.2014.881799. Epub 2014 Feb 4. Review. PubMed PMID: 24490905.

8: Pollesello P. Drug discovery and development for acute heart failure drugs: are expectations too high? Int J Cardiol. 2014 Mar 1;172(1):11-3. doi: 10.1016/j.ijcard.2013.12.136. Epub 2014 Jan 4. PubMed PMID: 24472177.

9: Givertz MM, Teerlink JR, Albert NM, Westlake Canary CA, Collins SP, Colvin-Adams M, Ezekowitz JA, Fang JC, Hernandez AF, Katz SD, Krishnamani R, Stough WG, Walsh MN, Butler J, Carson PE, Dimarco JP, Hershberger RE, Rogers JG, Spertus JA, Stevenson WG, Sweitzer NK, Tang WH, Starling RC. Acute decompensated heart failure: update on new and emerging evidence and directions for future research. J Card Fail. 2013 Jun;19(6):371-89. doi: 10.1016/j.cardfail.2013.04.002. Review. PubMed PMID: 23743486.

10: Zhang M, Mou T, Zhao Z, Peng C, Ma Y, Fang W, Zhang X. Synthesis and 18F-labeling of the analogues of Omecamtiv Mecarbil as a potential cardiac myosin imaging agent with PET. Nucl Med Biol. 2013 Jul;40(5):689-96. doi: 10.1016/j.nucmedbio.2013.02.013. Epub 2013 Apr 6. PubMed PMID: 23566883.