Danicamtiv

• CAS: 1970972-74-7
• Catalog Number: ACM1970972747
• Category: Activators
• Molecular Weight: 435.42
• Molecular Formula: C16H20F3N5O4S
• Description: Danicamtiv (MYK-491), an inotropic agent, is a selective allosteric activator of cardiac myosin. Danicamtiv increases cardiac systolic function and preserves mechanical efficiency.
• Synonyms: Danicamtiv; MYK-491; MYK 491; MYK491
• IUPAC Name: 4-(1-((3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl)sulfonyl)-1-fluoroethyl)-N-(isoxazol-3-yl)piperidine-1-carboxamide
• Canonical SMILES: FC(C1CCN(C(NC2=NOC=C2)=O)CC1)(C)S(C3=CN(C)N=C3C(F)F)(=O)=O
• InChI: 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)
• InChI Key: NREKKBAMVWQRES-UHFFFAOYSA-N
• Solubility: Soluble in DMSO
• Appearance: Solid powder
• Shelf Life: >2 years if stored properly
• Storage: Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
• Biological Target: A selective allosteric activator of cardiac myosin.
• Drug Formulation: This drug may be formulated in DMSO
• Elemental Analysis: C, 44.14; H, 4.63; F, 13.09; N, 16.08; O, 14.70; S, 7.36
• Exact Mass: 435.1188
• HS Tariff Code: 2934.99.9001
• 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.
• Shipping: 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.
• Stock Solution Storage: 0-4 °C for short term (days to weeks), or -20 °C for long term (months).