Aficamten

• CAS: 2364554-48-1
• Catalog Number: ACM2364554481
• Category: Inhibitors
• Molecular Weight: 337.38
• Molecular Formula: C18H19N5O2
• Description: Aficamten, also known as CK-3773274 and CK-274, is a Next-Generation Cardiac Myosin Inhibitor for the Treatment of Hypertrophic Cardiomyopathy. Aficamten was designed to provide a predicted human half-life (t1/2) appropriate for once a day (qd) dosing, to reach steady state within two weeks, to have no substantial cytochrome P450 induction or inhibition, and to have a wide therapeutic window in vivo with a clear pharmacokinetic/pharmacodynamic relationship. In a phase I clinical trial, aficamten demonstrated a human t1/2 similar to predictions and was able to reach steady state concentration within the desired two-week window.
• Synonyms: CK-3773274; CK3773274; CK 3773274; CK-274; CK274; CK 274
• IUPAC Name: N-[(1R)-5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl]-1-methyl-1H-pyrazole-4-carboxamide
• Canonical SMILES: O=C(C1=CN(C)N=C1)N[C@@H]2CCC3=C2C=CC(C4=NOC(CC)=N4)=C3
• InChI: InChI=1S/C18H19N5O2/c1-3-16-21-17(22-25-16)12-4-6-14-11(8-12)5-7-15(14)20-18(24)13-9-19-23(2)10-13/h4,6,8-10,15H,3,5,7H2,1-2H3,(H,20,24)/t15-/m1/s1
• InChI Key: IOVAZWDIRCRMTM-OAHLLOKOSA-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: Aficamten (CK-274) is a potent cardiac myosin inhibitor with an IC50 of 1.4 μM.
• Drug Formulation: This drug may be formulated in DMSO
• Elemental Analysis: C, 64.08; H, 5.68; N, 20.76; O, 9.48
• Exact Mass: 337.1539
• HS Tariff Code: 2934.99.9001
• In Vitro Activity: TBD
• In Vivo Activity: To assess the therapeutic window and PK/PD relationship relative to a clinical stage compound, the pharmacodynamic dose and exposure response of aficamten and mavacamten were measured by echocardiography in normal, Sprague-Dawley rats. Aficamten reduced FS (fractional shortening) in a dose-related manner, with a maximal reduction in FS between 70 and 80% relative to vehicle treatment observed 1 h after the highest dose of 4 mg/kg. To strengthen this hypothesis, the therapeutic window and the PK/PD relationship of aficamten was measured in dogs under a similar paradigm as described above for rats. Aficamten produced similar results in rats and dogs, with a free IC10 (IC10-free) of 0.0144 and 0.0178 μM and an IC50-free/IC10-free ratio of 9.9× and 13.0×, respectively.; Reference: J Med Chem. 2021 Oct 14;64(19):14142-14152. https://pubmed.ncbi.nlm.nih.gov/34606259/
• 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).