Omecamtiv mecarbil | CAS#873697-71-3 | myosin activator

MedKoo Cat#: 510321 | Name: Omecamtiv mecarbil

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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

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: 401.1863

Molecular Weight: 401.44

Elemental Analysis: C, 59.84; H, 6.03; F, 4.73; N, 17.45; O, 11.96

Price and Availability

Size	Price	Availability
10mg	USD 150.00	2 Weeks
25mg	USD 250.00	2 Weeks
50mg	USD 450.00	2 Weeks
100mg	USD 750.00	2 Weeks
200mg	USD 1,250.00	2 Weeks
500mg	USD 2,050.00	2 Weeks
1g	USD 3,450.00	2 Weeks
2g	USD 5,250.00	2 Weeks
5g	USD 8,650.00	2 Weeks

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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

Product Data

Instruction

View handling instruction

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/

	Solvent	mg/mL	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

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

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.

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:

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.

1: Shoji S, Mentz RJ. Beyond quadruple therapy: the potential roles for ivabradine, vericiguat, and omecamtiv mecarbil in the therapeutic armamentarium. Heart Fail Rev. 2024 Sep;29(5):949-955. doi: 10.1007/s10741-024-10412-y. Epub 2024 Jun 29. PMID: 38951303. 2: Li Y, Ma K, Dong Z, Gao S, Zhang J, Huang S, Yang J, Fang G, Li Y, Li X, Welch C, Griffin EL, Ramaswamy P, Valivullah Z, Liu X, Dong J, Wang DW, Du J, Chung WK, Li Y. Frameshift variants in C10orf71 cause dilated cardiomyopathy in human, mouse, and organoid models. J Clin Invest. 2024 Jun 17;134(12):e177172. doi: 10.1172/JCI177172. PMID: 38950288; PMCID: PMC11178530. 3: Auguin D, Robert-Paganin J, Réty S, Kikuti C, David A, Theumer G, Schmidt AW, Knölker HJ, Houdusse A. Omecamtiv mecarbil and Mavacamten target the same myosin pocket despite opposite effects in heart contraction. Nat Commun. 2024 Jun 7;15(1):4885. doi: 10.1038/s41467-024-47587-9. PMID: 38849353; PMCID: PMC11161628. 4: McGurk KA, Bilgehan N, Ware JS. Pharmacogenetic Influences Over Mavacamten Pharmacokinetics: Considerations for the Treatment of Individuals With Hypertrophic Cardiomyopathy. Circulation. 2024 Jun 4;149(23):1786-1788. doi: 10.1161/CIRCULATIONAHA.123.066916. Epub 2024 Jun 3. PMID: 38829931; PMCID: PMC7616064. 5: Monte E, Furihata T, Wang G, Perea-Gil I, Wei E, Chaib H, Nair R, Guevara JV, Mares R, Cheng X, Zhuge Y, Black K, Serrano R, Dagan-Rosenfeld O, Maguire P, Mercola M, Karakikes I, Wu JC, Snyder MP. Personalized transcriptome signatures in a cardiomyopathy stem cell biobank. bioRxiv [Preprint]. 2024 May 14:2024.05.10.593618. doi: 10.1101/2024.05.10.593618. PMID: 38798547; PMCID: PMC11118309. 6: Lindberg F, Øigaard N, Metra M, Rosano GMC, Dahlström U, Mol P, Hage C, Lund LH, Savarese G. Eligibility for omecamtiv mecarbil in a real-world heart failure population: Data from the Swedish Heart Failure Registry. PLoS One. 2024 May 24;19(5):e0303348. doi: 10.1371/journal.pone.0303348. PMID: 38787867; PMCID: PMC11125482. 7: Awinda PO, Vander Top BJ, Turner KL, Tanner BCW. Danicamtiv affected isometric force and cross-bridge kinetics similarly in skinned myocardial strips from male and female rats. J Muscle Res Cell Motil. 2024 Sep;45(3):115-122. doi: 10.1007/s10974-024-09669-5. Epub 2024 May 8. PMID: 38717549. 8: Haryani A, Sangwan A. New Pharmacotherapeutic Classes for the Management of Heart Failure: A Narrative Review. Cureus. 2024 Mar 29;16(3):e57180. doi: 10.7759/cureus.57180. PMID: 38681432; PMCID: PMC11056082. 9: Zhu L, Shi P. Intellectual landscapes and emerging trends of non-steroidal mineralocorticoid receptor antagonists: a bibliometric and visual analysis. Int Urol Nephrol. 2024 Sep;56(9):3079-3090. doi: 10.1007/s11255-024-04059-9. Epub 2024 Apr 25. PMID: 38662266. 10: Hattori Y, Hattori K, Ishii K, Kobayashi M. Challenging and target-based shifting strategies for heart failure treatment: An update from the last decades. Biochem Pharmacol. 2024 Jun;224:116232. doi: 10.1016/j.bcp.2024.116232. Epub 2024 Apr 20. PMID: 38648905. 11: Karimi E, Gohlke J, van der Borgh M, Lindqvist J, Hourani Z, Kolb J, Cossette S, Lawlor MW, Ottenheijm C, Granzier H. Characterization of NEB pathogenic variants in patients reveals novel nemaline myopathy disease mechanisms and omecamtiv mecarbil force effects. Acta Neuropathol. 2024 Apr 18;147(1):72. doi: 10.1007/s00401-024-02726-w. PMID: 38634969; PMCID: PMC11026289. 12: Zhou S, Liu Y, Huang X, Wu C, Pórszász R. Omecamtiv Mecarbil in the treatment of heart failure: the past, the present, and the future. Front Cardiovasc Med. 2024 Mar 19;11:1337154. doi: 10.3389/fcvm.2024.1337154. PMID: 38566963; PMCID: PMC10985333. 13: Kourek C, Briasoulis A, Papamichail A, Xanthopoulos A, Tsougos E, Farmakis D, Paraskevaidis I. Beyond Quadruple Therapy and Current Therapeutic Strategies in Heart Failure with Reduced Ejection Fraction: Medical Therapies with Potential to Become Part of the Therapeutic Armamentarium. Int J Mol Sci. 2024 Mar 7;25(6):3113. doi: 10.3390/ijms25063113. PMID: 38542088; PMCID: PMC10969833. 14: Sergeeva KV, Tyganov SA, Zaripova KA, Bokov RO, Nikitina LV, Konstantinova TS, Kalamkarov GR, Shenkman BS. Mechanical and signaling responses of unloaded rat soleus muscle to chronically elevated β-myosin activity. Arch Biochem Biophys. 2024 Apr;754:109961. doi: 10.1016/j.abb.2024.109961. Epub 2024 Mar 14. PMID: 38492659. 15: D'Amato A, Prosperi S, Severino P, Myftari V, Labbro Francia A, Cestiè C, Pierucci N, Marek-Iannucci S, Mariani MV, Germanò R, Fanisio F, Lavalle C, Maestrini V, Badagliacca R, Mancone M, Fedele F, Vizza CD. Current Approaches to Worsening Heart Failure: Pathophysiological and Molecular Insights. Int J Mol Sci. 2024 Jan 26;25(3):1574. doi: 10.3390/ijms25031574. PMID: 38338853; PMCID: PMC10855688. 16: Jani VP, Song T, Gao C, Gong H, Sadayappan S, Kass DA, Irving TC, Ma W. The structural OFF and ON states of myosin can be decoupled from the biochemical super- and disordered-relaxed states. PNAS Nexus. 2024 Jan 30;3(2):pgae039. doi: 10.1093/pnasnexus/pgae039. PMID: 38328779; PMCID: PMC10849796. 17: Adamo M, Metra M, Claggett BL, Miao ZM, Diaz R, Felker GM, McMurray JJV, Solomon SD, Biering-Sørensen T, Divanji PH, Heitner SB, Kupfer S, Malik FI, Teerlink JR; GALACTIC-HF Investigators and Patients. Tricuspid Regurgitation and Clinical Outcomes in Heart Failure With Reduced Ejection Fraction. JACC Heart Fail. 2024 Mar;12(3):552-563. doi: 10.1016/j.jchf.2023.11.018. Epub 2024 Jan 31. PMID: 38300212. 18: Chan JCH, Siddiqui A. Pharmacological Treatment of Heart Failure: Recent Advances. Curr Cardiol Rev. 2024;20(2):29-38. doi: 10.2174/011573403X270178231228061314. PMID: 38284706; PMCID: PMC11107472. 19: Felker GM, Solomon SD, Metra M, Mcmurray JJV, Diaz R, Claggett B, Lanfear DE, Vandekerckhove H, Biering-Sørensen T, Lopes RD, Arias-Mendoza A, Momomura SI, Corbalan R, Ramires FJA, Zannad F, Heitner SB, Divanji PH, Kupfer S, Malik FI, Teerlink JR. Cardiac Troponin and Treatment Effects of Omecamtiv Mecarbil: Results From the GALACTIC-HF Study. J Card Fail. 2024 Jun;30(6):755-763. doi: 10.1016/j.cardfail.2023.11.021. Epub 2024 Jan 11. PMID: 38215932. 20: Karimi E, van der Borgh M, Lindqvist J, Gohlke J, Hourani Z, Kolb J, Cossette S, Lawlor MW, Ottenheijm C, Granzier H. Characterization of NEB mutations in patients reveals novel nemaline myopathy disease mechanisms and omecamtiv mecarbil force effects. bioRxiv [Preprint]. 2023 Dec 21:2023.12.20.572678. doi: 10.1101/2023.12.20.572678. Update in: Acta Neuropathol. 2024 Apr 18;147(1):72. doi: 10.1007/s00401-024-02726-w. PMID: 38187705; PMCID: PMC10769406.