MedKoo Biosciences, Inc.
Tel:   +1-919-636-5577    Fax:   +1-919-980-4831    Email:   sales@medkoo.com
Search
Login Register
Search
MedKoo Cat#: 591242 | Name: Danicamtiv
Featured New

Description:

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

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

Danicamtiv
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
5mg USD 150.00 Ready to ship
10mg USD 250.00 Ready to ship
25mg USD 550.00 Ready to ship
50mg USD 950.00 Ready to ship
Bulk Inquiry
Buy Now
Add to Cart
Related CAS #
No Data
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
More Info
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.
Solvent mg/mL mM
Solubility
DMSO 50.0 114.83
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 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.
1: Landim-Vieira M, Knollmann BC. Danicamtiv Recruits Myosin Motors to Aid the Failing Heart. Circ Res. 2023 Aug 18;133(5):444-446. doi: 10.1161/CIRCRESAHA.123.323366. Epub 2023 Aug 17. PMID: 37590375. 2: Lehman SJ, Crocini C, Leinwand LA. Targeting the sarcomere in inherited cardiomyopathies. Nat Rev Cardiol. 2022 Jun;19(6):353-363. doi: 10.1038/s41569-022-00682-0. Epub 2022 Mar 18. PMID: 35304599; PMCID: PMC9119933. 3: Kooiker KB, Mohran S, Turner KL, Ma W, Martinson A, Flint G, Qi L, Gao C, Zheng Y, McMillen TS, Mandrycky C, Mahoney-Schaefer M, Freeman JC, Costales Arenas EG, Tu AY, Irving TC, Geeves MA, Tanner BCW, Regnier M, Davis J, Moussavi-Harami F. Danicamtiv Increases Myosin Recruitment and Alters Cross- Bridge Cycling in Cardiac Muscle. Circ Res. 2023 Aug 18;133(5):430-443. doi: 10.1161/CIRCRESAHA.123.322629. Epub 2023 Jul 20. PMID: 37470183; PMCID: PMC10434831. 4: Kooiker KB, Mohran S, Turner KL, Ma W, Flint G, Qi L, Gao C, Zheng Y, McMillen TS, Mandrycky C, Martinson A, Mahoney-Schaefer M, Freeman JC, Costales Arenas EG, Tu AY, Irving TC, Geeves MA, Tanner BCW, Regnier M, Davis J, Moussavi-Harami F. Danicamtiv increases myosin recruitment and alters the chemomechanical cross bridge cycle in cardiac muscle. bioRxiv [Preprint]. 2023 Feb 3:2023.01.31.526380. doi: 10.1101/2023.01.31.526380. Update in: Circ Res. 2023 Jul 20;: PMID: 36778318; PMCID: PMC9915609. 5: 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; PMCID: PMC8477869. 6: 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. 7: Ráduly AP, Sárkány F, Kovács MB, Bernát B, Juhász B, Szilvássy Z, Porszász R, Horváth B, Szentandrássy N, Nánási P, Csanádi Z, Édes I, Tóth A, Papp Z, Priksz D, Borbély A. The Novel Cardiac Myosin Activator Danicamtiv Improves Cardiac Systolic Function at the Expense of Diastolic Dysfunction In Vitro and In Vivo: Implications for Clinical Applications. Int J Mol Sci. 2022 Dec 27;24(1):446. doi: 10.3390/ijms24010446. PMID: 36613900; PMCID: PMC9820393. 8: 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. 9: 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. 10: 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. 11: Lanfear DE, Reza N. Myosin-Related Dilated Cardiomyopathy: Another Elephant Emerges From Darkness. J Am Coll Cardiol. 2022 Oct 11;80(15):1462-1464. doi: 10.1016/j.jacc.2022.08.749. PMID: 36202535.