Aficamten - CAS# 2364554-48-1

Aficamten, CAS No. 2364554-48-1, 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. Aficamten (CK-274) is a potent cardiac myosin inhibitor with an IC50 of 1.4 μM. Aficamten can be used for the research of hypertrophic cardiomyopathy (HCM).

Product information

CAS Number: 2364554-48-1

Molecular Weight: 337.38

Formula: C18H19N5O2

Chemical 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

Smiles: CCC1=NC(=NO1)C1=CC2CC[C@@H](NC(=O)C3C=NN(C)C=3)C=2C=C1

InChiKey: IOVAZWDIRCRMTM-OAHLLOKOSA-N

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

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: To be determined

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vivo:

Aficamten is a next-generation cardiac myosin inhibitor that provides a projected human half-life appropriate for once a day dosing, reaching steady state within two weeks, and demonstrates a wide therapeutic window in vivo with a clear PK/PD relationship. Aficamten exhibits moderate oral bioavailability (mouse 98%, rat 55%, rat 58%, rat 79%, dog 45%, monkey 41%) following oral administration (mouse 1 mg/kg, rat 2 mg/kg, rat 3 mg/kg, rat 8 mg/kg, dog 1 mg/kg and monkey 1 mg/kg). Aficamten exhibits terminal elimination half-lives (mouse 4.5 h, rat 3.0 h, dog 33.8 h and, monkey 8.1 h) following intravenous administration (mouse 0.5 mg/kg, rat 1 mg/kg, dog 1 mg/kg and monkey 1.0 mg/kg).

References:

1. Chuang C, Collibee S, Ashcraft L, Wang W, Vander Wal M, Wang X, Hwee DT, Wu Y, Wang J, Chin ER, Cremin P, Zamora J, Hartman J, Schaletzky J, Wehri E, Robertson LA, Malik FI, Morgan BP. Discovery of Aficamten (CK-274), a Next-Generation Cardiac Myosin Inhibitor for the Treatment of Hypertrophic Cardiomyopathy. J Med Chem. 2021 Oct 14;64(19):14142-14152. doi: 10.1021/acs.jmedchem.1c01290. Epub 2021 Oct 4. PMID: 34606259.

Products are for research use only. Not for human use.