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Danicamtiv (MYK-491)

Synonyms: SAR 440181

Catalog No.S9948 Purity: 99.13%

Danicamtiv (MYK-491, SAR 440181) is a novel cardiac myosin activator that enhances cardiomyocyte contraction.

Danicamtiv (MYK-491) Chemical Structure

CAS: 1970972-74-7

Selleck's Danicamtiv (MYK-491) has been cited by 1 publication

Purity & Quality Control

Batch: S994801 DMSO] 87 mg/mL] false] Water] Insoluble] false] Ethanol] Insoluble] false Purity: 99.13%

99.13

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Choose Selective Cardiac Myosin Inhibitors

Biological Activity

Description

Danicamtiv (MYK-491, SAR 440181) is a novel cardiac myosin activator that enhances cardiomyocyte contraction.

Targets

cardiac myosin ^[1]

In vitro
In vitro	Danicamtiv metabolism pathways in vitro included CYP-mediated amide-cleavage, N-demethylation, as well as isoxazole- and piperidine-ring-opening.Danicamtiv show high permeability and no efflux in a Caco-2 cell line.<sup><a class="sref" href="#s_ref">[2]</a></sup>
Cell Research	Cell lines	Caco-2/TC7 cell lines, male human hepatocytes
	Concentrations	1 µM, 10 µM
	Incubation Time	0, 2, 4, 6, 8, and 24 h
	Method	Incubations of plated human hepatocytes (1.4 million viable cells/mL, 0.2 mL, n = 2) with danicamtiv (1 µM) are performed in a cell culture incubator (37 °C, 5% CO<sub>2</sub>, 95% humidity). Incubations are quenched with 200 µL of ACN containing 50 nM CBZ internal standard at incubation times 0, 2, 4, 6, 8, and 24 h. Supernatants are analysed by LC-MS/MS for the analysis of danicamtiv from preclinical pharmacokinetic studies. Caco-2 cells are seeded on 96-well cell culture plates with PCF membrane filters and maintained for 21/25 days post-seeding with culture medium exchanged every 4th day. The bidirectional permeability (efflux) experiments are conducted on a TECAN automated liquid handling platform. Danicamtiv is examined at 1 and 10 μM, permeability controls are tested at 10 μM, and efflux controls are tested either at 2 μM or 1 μM in duplicate wells.

In Vivo
In vivo	Danicamtiv selectively enhances cardiac actomyosin activity, the molecular force‐generating unit of the sarcomere, prolonging contraction while preserving actin-myosin detachment, allowing relaxation, and without impacting Ca2+ homeostasis.<sup><a class="sref" href="#s_ref">[1]</a></sup>
Animal Research	Animal Models	male beagle dogs
	Dosages	2–3 mg/kg
	Administration	p.o. , i. pl.

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2024-01-11)
NCT03447990	Completed	Heart Failure With Reduced Ejection Fraction\|Dilated Cardiomyopathy	Bristol-Myers Squibb	February 6 2018	Phase 1\|Phase 2

References
[1] Adriaan A Voors, et al. Eur J Heart Fail. 2020 Sep;22(9):1649-1658. [2] Grillo MP, et al. Xenobiotica. 2021 Feb;51(2):222-238.

References

Chemical lnformation & Solubility

Molecular Weight	435.42	Formula	C₁₆H₂₀F₃N₅O₄S
CAS No.	1970972-74-7	SDF	--
Smiles	C[N]1C=C(C(=N1)C(F)F)[S](=O)(=O)C(C)(F)C2CCN(CC2)C(=O)NC3=NOC=C3
Storage (From the date of receipt)	3 years -20°C powder	Storage of Stock Solutions Aliquot the stock solutions to avoid repeated freeze-thaw cycles	1 year-80°Cin solvent
Storage (From the date of receipt)	3 years -20°C powder		1 month-20°Cin solvent

In vitro
Batch:

DMSO : 87 mg/mL ( (199.8 mM)； Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble

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In vivo
Batch:

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In vivo Formulation Calculator

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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