Aficamten | CAS# 2364554-48-1 | Next-Generation Cardiac Myosin Inhibitor

MedKoo Cat#: 575791 | Name: Aficamten

Description:

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

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.

Chemical Structure

Aficamten

CAS#2364554-48-1

Theoretical Analysis

MedKoo Cat#: 575791

Name: Aficamten

CAS#: 2364554-48-1

Chemical Formula: C18H19N5O2

Exact Mass: 337.1539

Molecular Weight: 337.38

Elemental Analysis: C, 64.08; H, 5.68; N, 20.76; O, 9.48

Price and Availability

Size	Price	Availability
1mg	USD 90.00	Ready to ship
5mg	USD 210.00	Ready to ship
10mg	USD 350.00	Ready to ship
25mg	USD 750.00	Ready to ship
50mg	USD 1,350.00	Ready to ship
100mg	USD 2,350.00	Ready to ship

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Related CAS #

No Data

Synonym

Aficamten; CK-3773274; CK3773274; CK 3773274; CK-274; CK274; CK 274;

IUPAC/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

InChi Key

IOVAZWDIRCRMTM-OAHLLOKOSA-N

InChi Code

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

SMILES Code

O=C(C1=CN(C)N=C1)N[C@@H]2CCC3=C2C=CC(C4=NOC(CC)=N4)=C3

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

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#A21T11K08

QC Data

View QC data: current batch, Lot#A21T11K08

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Aficamten (CK-274) is a potent cardiac myosin inhibitor with an IC50 of 1.4 μM.

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/

	Solvent	mg/mL	mM
Solubility
	DMSO	91.0	269.73

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 337.38 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.

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:

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.

In vitro protocol:

TBD

In vivo protocol:

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. 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: Maron MS, Masri A, Choudhury L, Olivotto I, Saberi S, Wang A, Garcia-Pavia P, Lakdawala NK, Nagueh SF, Rader F, Tower-Rader A, Turer AT, Coats C, Fifer MA, Owens A, Solomon SD, Watkins H, Barriales-Villa R, Kramer CM, Wong TC, Paige SL, Heitner SB, Kupfer S, Malik FI, Meng L, Wohltman A, Abraham T; REDWOOD-HCM Steering Committee and Investigators. Phase 2 Study of Aficamten in Patients With Obstructive Hypertrophic Cardiomyopathy. J Am Coll Cardiol. 2023 Jan 3;81(1):34-45. doi: 10.1016/j.jacc.2022.10.020. PMID: 36599608. 4: Kawana M, Spudich JA, Ruppel KM. Hypertrophic cardiomyopathy: Mutations to mechanisms to therapies. Front Physiol. 2022 Sep 26;13:975076. doi: 10.3389/fphys.2022.975076. Erratum in: Front Physiol. 2022 Dec 12;13:1111059. PMID: 36225299; PMCID: PMC9548533. 5: Morelli C, Ingrasciotta G, Jacoby D, Masri A, Olivotto I. Sarcomere protein modulation: The new frontier in cardiovascular medicine and beyond. Eur J Intern Med. 2022 Aug;102:1-7. doi: 10.1016/j.ejim.2022.04.020. Epub 2022 May 6. PMID: 35534374. 6: Masri A, Olivotto I. Cardiac Myosin Inhibitors as a Novel Treatment Option for Obstructive Hypertrophic Cardiomyopathy: Addressing the Core of the Matter. J Am Heart Assoc. 2022 May 3;11(9):e024656. doi: 10.1161/JAHA.121.024656. Epub 2022 May 3. PMID: 35502770; PMCID: PMC9238628. 7: Malik FI, Robertson LA, Armas DR, Robbie EP, Osmukhina A, Xu D, Li H, Solomon SD. A Phase 1 Dose-Escalation Study of the Cardiac Myosin Inhibitor Aficamten in Healthy Participants. JACC Basic Transl Sci. 2022 Aug 10;7(8):763-775. doi: 10.1016/j.jacbts.2022.04.008. PMID: 36061336; PMCID: PMC9436819. 8: Sharpe AN, Oldach MS, Rivas VN, Kaplan JL, Walker AL, Kovacs SL, Hwee DT, Cremin P, Morgan BP, Malik FI, Harris SP, Stern JA. Effects of Aficamten on cardiac contractility in a feline translational model of hypertrophic cardiomyopathy. Sci Rep. 2023 Jan 2;13(1):32. doi: 10.1038/s41598-022-26630-z. PMID: 36593243; PMCID: PMC9807554. 9: Mozzini C, Pagani M. THE HEART FAILURE KNIGHTS. Curr Probl Cardiol. 2023 May 25:101834. doi: 10.1016/j.cpcardiol.2023.101834. Epub ahead of print. PMID: 37244515. 10: Nair A, Xie L, Silva Enciso JE. Myosin Inhibitors: The Next Generation. J Am Coll Cardiol. 2023 Jan 3;81(1):46-48. doi: 10.1016/j.jacc.2022.10.018. PMID: 36599609. 11: Papp Z. Moderating the Myosin Motor to Treat Hypertrophic Cardiomyopathy. JACC Basic Transl Sci. 2022 Aug 22;7(8):776-778. doi: 10.1016/j.jacbts.2022.06.006. PMID: 36061334; PMCID: PMC9436807. 12: Sharpe AN, Oldach MS, Kaplan JL, Rivas V, Kovacs SL, Hwee DT, Morgan BP, Malik FI, Harris SP, Stern JA. Pharmacokinetics of a single dose of Aficamten (CK-274) on cardiac contractility in a A31P MYBPC3 hypertrophic cardiomyopathy cat model. J Vet Pharmacol Ther. 2023 Jan;46(1):52-61. doi: 10.1111/jvp.13103. Epub 2022 Nov 16. PMID: 36382714; PMCID: PMC10099566. 13: Mathai S, Williams L. Left ventricular outflow tract obstruction in hypertrophic cardiomyopathy and the impact of mavacamten. Ther Adv Chronic Dis. 2022 Nov 15;13:20406223221136074. doi: 10.1177/20406223221136074. PMID: 36407022; PMCID: PMC9666864. 14: Autore C, Bariani R, Bauce B, Biagini E, Canepa M, Castelletti S, Crotti L, Limongelli G, Merlo M, Monda E, Pio Loco Detto Gava C, Parisi V, Tini G, Imazio M. From the phenotype to precision medicine: an update on the cardiomyopathies diagnostic workflow. J Cardiovasc Med (Hagerstown). 2023 May 1;24(Suppl 2):e178-e186. doi: 10.2459/JCM.0000000000001424. PMID: 37186568. 15: Packard E, de Feria A, Peshin S, Reza N, Owens AT. Contemporary Therapies and Future Directions in the Management of Hypertrophic Cardiomyopathy. Cardiol Ther. 2022 Dec;11(4):491-507. doi: 10.1007/s40119-022-00283-5. Epub 2022 Oct 15. PMID: 36243823; PMCID: PMC9652179. 16: Altibi A, Alani A, Zhao Y, Masri A. Baseline and Longitudinal Imaging of Hypertrophic Cardiomyopathy in the Era of Emerging Therapeutics. Curr Cardiol Rep. 2023 Jun;25(6):583-595. doi: 10.1007/s11886-023-01883-w. Epub 2023 Apr 27. PMID: 37103749. 17: Rosenzveig A, Garg N, Rao SJ, Kanwal AK, Kanwal A, Aronow WS, Martinez MW. Current and emerging pharmacotherapy for the management of hypertrophic cardiomyopathy. Expert Opin Pharmacother. 2023 Jun 4:1-12. doi: 10.1080/14656566.2023.2219840. Epub ahead of print. PMID: 37272195.