Danicamtiv
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MedKoo CAT#: 591242

CAS#: 1970972-74-7

Description: Danicamtiv (MYK-491), an inotropic agent, is a selective allosteric activator of cardiac myosin. Danicamtiv increases cardiac systolic function and preserves mechanical efficiency.


Chemical Structure

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Danicamtiv
CAS# 1970972-74-7

Theoretical Analysis

MedKoo Cat#: 591242
Name: Danicamtiv
CAS#: 1970972-74-7
Chemical Formula: C16H20F3N5O4S
Exact Mass: 435.1188
Molecular Weight: 435.42
Elemental Analysis: C, 44.14; H, 4.63; F, 13.09; N, 16.08; O, 14.70; S, 7.36

Price and Availability

Size Price Availability Quantity
1.0mg USD 90.0 Ready to ship
5.0mg USD 210.0 Ready to ship
10.0mg USD 350.0 Ready to ship
25.0mg USD 550.0 Ready to ship
50.0mg USD 950.0 Ready to ship
100.0mg USD 1650.0 Ready to ship
200.0mg USD 2250.0 Ready to ship
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Synonym: Danicamtiv; MYK-491; MYK 491; MYK491;

IUPAC/Chemical Name: 4-(1-((3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl)sulfonyl)-1-fluoroethyl)-N-(isoxazol-3-yl)piperidine-1-carboxamide

InChi Key: NREKKBAMVWQRES-UHFFFAOYSA-N

InChi Code: InChI=1S/C16H20F3N5O4S/c1-16(19,29(26,27)11-9-23(2)21-13(11)14(17)18)10-3-6-24(7-4-10)15(25)20-12-5-8-28-22-12/h5,8-10,14H,3-4,6-7H2,1-2H3,(H,20,22,25)

SMILES Code: FC(C1CCN(C(NC2=NOC=C2)=O)CC1)(C)S(C3=CN(C)N=C3C(F)F)(=O)=O

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

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

Biological target: A selective allosteric activator of cardiac myosin.
In vitro activity: Danicamtiv metabolism pathways in vitro included CYP-mediated amide-cleavage, N-demethylation, as well as isoxazole- and piperidine-ring-opening. Danicamtiv clearance in vivo was low across species with 15.5, 15.3, 1.6, and 5.7 mL/min/kg in mouse, rat, dog, and monkey, respectively. Volume of distribution ranged from 0.24 L/kg in mouse to 1.7 L/kg in rat. Oral bioavailability ranged from 26% in mouse to 108% in dog. Simple allometric scaling prediction of human plasma clearance, volume of distribution, and half-life was 0.64 mL/min/kg, 0.98 L/kg, and 17.7 h, respectively. Danicamtiv preclinical attributes and predicted human pharmacokinetics supported advancement toward clinical development. Reference: Grillo MP, Markova S, Evanchik M, Trellu M, Moliner P, Brun P, Perreard-Dumaine A, Vicat P, Driscoll JP, Carlson TJ. Preclinical in vitro and in vivo pharmacokinetic properties of danicamtiv, a new targeted myosin activator for the treatment of dilated cardiomyopathy. Xenobiotica. 2021 Feb;51(2):222-238. doi: 10.1080/00498254.2020.1839982. Epub 2020 Nov 16. PMID: 33078965.
In vivo activity: Danicamtiv increased ATPase activity and calcium sensitivity in LV and LA myofibrils/muscle fibres. In dogs with heart failure, danicamtiv improved LV stroke volume (+10.6 mL, P < 0.05) and LA emptying fraction (+10.7%, P < 0.05). In patients with HFrEF (mean age 60 years, 25% women, ischaemic heart disease 48%, mean LV ejection fraction 32%), treatment-emergent adverse events, mostly mild, were reported in 17 patients (57%) receiving danicamtiv and 4 patients (40%) receiving placebo. Danicamtiv (at plasma concentrations ≥2000 ng/mL) increased stroke volume (up to +7.8 mL, P < 0.01), improved global longitudinal (up to -1.0%, P < 0.05) and circumferential strain (up to -3.3%, P < 0.01), decreased LA minimal volume index (up to -2.4 mL/m2 , P < 0.01) and increased LA function index (up to 6.1, P < 0.01), when compared with placebo. Danicamtiv was well tolerated and improved LV systolic function in patients with HFrEF. A marked improvement in LA volume and function was also observed in patients with HFrEF, consistent with pre-clinical findings of direct activation of LA contractility. Reference: Voors AA, Tamby JF, Cleland JG, Koren M, Forgosh LB, Gupta D, Lund LH, Camacho A, Karra R, Swart HP, Pellicori P, Wagner F, Hershberger RE, Prasad N, Anderson R, Anto A, Bell K, Edelberg JM, Fang L, Henze M, Kelly C, Kurio G, Li W, Wells K, Yang C, Teichman SL, Del Rio CL, Solomon SD. Effects of danicamtiv, a novel cardiac myosin activator, in heart failure with reduced ejection fraction: experimental data and clinical results from a phase 2a trial. Eur J Heart Fail. 2020 Sep;22(9):1649-1658. doi: 10.1002/ejhf.1933. Epub 2020 Jul 10. PMID: 32558989; PMCID: PMC7689751.

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 50.0 114.83

Preparing Stock Solutions

The following data is based on the product molecular weight 435.42 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: Grillo MP, Markova S, Evanchik M, Trellu M, Moliner P, Brun P, Perreard-Dumaine A, Vicat P, Driscoll JP, Carlson TJ. Preclinical in vitro and in vivo pharmacokinetic properties of danicamtiv, a new targeted myosin activator for the treatment of dilated cardiomyopathy. Xenobiotica. 2021 Feb;51(2):222-238. doi: 10.1080/00498254.2020.1839982. Epub 2020 Nov 16. PMID: 33078965.
In vitro protocol: Grillo MP, Markova S, Evanchik M, Trellu M, Moliner P, Brun P, Perreard-Dumaine A, Vicat P, Driscoll JP, Carlson TJ. Preclinical in vitro and in vivo pharmacokinetic properties of danicamtiv, a new targeted myosin activator for the treatment of dilated cardiomyopathy. Xenobiotica. 2021 Feb;51(2):222-238. doi: 10.1080/00498254.2020.1839982. Epub 2020 Nov 16. PMID: 33078965.
In vivo protocol: Voors AA, Tamby JF, Cleland JG, Koren M, Forgosh LB, Gupta D, Lund LH, Camacho A, Karra R, Swart HP, Pellicori P, Wagner F, Hershberger RE, Prasad N, Anderson R, Anto A, Bell K, Edelberg JM, Fang L, Henze M, Kelly C, Kurio G, Li W, Wells K, Yang C, Teichman SL, Del Rio CL, Solomon SD. Effects of danicamtiv, a novel cardiac myosin activator, in heart failure with reduced ejection fraction: experimental data and clinical results from a phase 2a trial. Eur J Heart Fail. 2020 Sep;22(9):1649-1658. doi: 10.1002/ejhf.1933. Epub 2020 Jul 10. PMID: 32558989; PMCID: PMC7689751.

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1: Voors AA, Tamby JF, Cleland JG, Koren M, Forgosh LB, Gupta D, Lund LH, Camacho A, Karra R, Swart HP, Pellicori P, Wagner F, Hershberger RE, Prasad N, Anderson R, Anto A, Bell K, Edelberg JM, Fang L, Henze M, Kelly C, Kurio G, Li W, Wells K, Yang C, Teichman SL, Del Rio CL, Solomon SD. Effects of danicamtiv, a novel cardiac myosin activator, in heart failure with reduced ejection fraction: experimental data and clinical results from a phase 2a trial. Eur J Heart Fail. 2020 Sep;22(9):1649-1658. doi: 10.1002/ejhf.1933. Epub 2020 Jul 10. PMID: 32558989; PMCID: PMC7689751.

2: Grillo MP, Markova S, Evanchik M, Trellu M, Moliner P, Brun P, Perreard- Dumaine A, Vicat P, Driscoll JP, Carlson TJ. Preclinical in vitro and in vivo pharmacokinetic properties of danicamtiv, a new targeted myosin activator for the treatment of dilated cardiomyopathy. Xenobiotica. 2021 Feb;51(2):222-238. doi: 10.1080/00498254.2020.1839982. Epub 2020 Nov 16. PMID: 33078965.

3: Shen S, Sewanan LR, Jacoby DL, Campbell SG. Danicamtiv Enhances Systolic Function and Frank-Starling Behavior at Minimal Diastolic Cost in Engineered Human Myocardium. J Am Heart Assoc. 2021 Jun 15;10(12):e020860. doi: 10.1161/JAHA.121.020860. Epub 2021 Jun 7. PMID: 34096321.

4: Alsulami K, Marston S. Small Molecules acting on Myofilaments as Treatments for Heart and Skeletal Muscle Diseases. Int J Mol Sci. 2020 Dec 16;21(24):9599. doi: 10.3390/ijms21249599. PMID: 33339418; PMCID: PMC7767104.

5: Bernier TD, Buckley LF. Cardiac Myosin Activation for the Treatment of Systolic Heart Failure. J Cardiovasc Pharmacol. 2021 Jan 1;77(1):4-10. doi: 10.1097/FJC.0000000000000929. PMID: 33165138; PMCID: PMC7779665.