Aficamten

Aficamten
Clinical data
Other names	CK-274
Identifiers
	IUPAC name N-[(1R)-5-(5-Ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl]-1-methylpyrazole-4-carboxamide;
CAS Number	2364554-48-1;
PubChem CID	139331495;
ChemSpider	114935503;
UNII	B1I77MH6K1;
ChEMBL	ChEMBL4847050;
Chemical and physical data
Formula	C18H19N5O2
Molar mass	337.383 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CCC1=NC(=NO1)C2=CC3=C(C=C2)[C@@H](CC3)NC(=O)C4=CN(N=C4)C;
	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; Key:IOVAZWDIRCRMTM-OAHLLOKOSA-N;

Aficamten (CK-274) is a cardiac myosin inhibitor^[1] developed by Cytokinetics for the treatment of obstructive hypertrophic cardiomyopathy.^[2]^[3]^[4]

References

^ Chuang, Chihyuan; Collibee, Scott; Ashcraft, Luke; Wang, Wenyue; Vander Wal, Mark; Wang, Xiaolin; Hwee, Darren T.; Wu, Yangsong; Wang, Jingying; Chin, Eva R.; Cremin, Peadar; Zamora, Jeanelle; Hartman, James; Schaletzky, Julia; Wehri, Eddie; Robertson, Laura A.; Malik, Fady I.; Morgan, Bradley P. (14 October 2021). "Discovery of Aficamten (CK-274), a Next-Generation Cardiac Myosin Inhibitor for the Treatment of Hypertrophic Cardiomyopathy". Journal of Medicinal Chemistry. 64 (19): 14142–14152. doi:10.1021/acs.jmedchem.1c01290. ISSN 0022-2623. PMID 34606259. S2CID 238355647.
^ Zhao, Xue; Liu, Hongzhong; Tian, Wei; Fang, Ligang; Yu, Mengyang; Wu, Xiaofei; Liu, Aijing; Wan, Ruijie; Li, Li; Luo, Jinghui; Li, Yuqiong; Liu, Bo; He, Yu; Chen, Xiaowen; Li, Yuan; Xu, Donghong; Wang, Hongyun; Han, Xiaohong (2023). "Safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple doses of aficamten in healthy Chinese participants: a randomized, double-blind, placebo-controlled, phase 1 study". Frontiers in Pharmacology. 14. doi:10.3389/fphar.2023.1227470. PMC 10482267. PMID 37680714.
^ Sebastian, Sneha Annie; Padda, Inderbir; Lehr, Eric J.; Johal, Gurpreet (September 2023). "Aficamten: A Breakthrough Therapy for Symptomatic Obstructive Hypertrophic Cardiomyopathy". American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions. 23 (5): 519–532. doi:10.1007/s40256-023-00599-0. ISSN 1179-187X. PMID 37526885. S2CID 260348901.
^ Maron, Martin S.; Masri, Ahmad; Choudhury, Lubna; Olivotto, Iacopo; Saberi, Sara; Wang, Andrew; Garcia-Pavia, Pablo; Lakdawala, Neal K.; Nagueh, Sherif F.; Rader, Florian; Tower-Rader, Albree; Turer, Aslan T.; Coats, Caroline; Fifer, Michael A.; Owens, Anjali; Solomon, Scott D.; Watkins, Hugh; Barriales-Villa, Roberto; Kramer, Christopher M.; Wong, Timothy C.; Paige, Sharon L.; Heitner, Stephen B.; Kupfer, Stuart; Malik, Fady I.; Meng, Lisa; Wohltman, Amy; Abraham, Theodore (January 2023). "Phase 2 Study of Aficamten in Patients With Obstructive Hypertrophic Cardiomyopathy". Journal of the American College of Cardiology. 81 (1): 34–45. doi:10.1016/j.jacc.2022.10.020. hdl:2158/1295661. PMID 36599608. S2CID 255472935.

[1] Chuang, Chihyuan; Collibee, Scott; Ashcraft, Luke; Wang, Wenyue; Vander Wal, Mark; Wang, Xiaolin; Hwee, Darren T.; Wu, Yangsong; Wang, Jingying; Chin, Eva R.; Cremin, Peadar; Zamora, Jeanelle; Hartman, James; Schaletzky, Julia; Wehri, Eddie; Robertson, Laura A.; Malik, Fady I.; Morgan, Bradley P. (14 October 2021). "Discovery of Aficamten (CK-274), a Next-Generation Cardiac Myosin Inhibitor for the Treatment of Hypertrophic Cardiomyopathy". Journal of Medicinal Chemistry. 64 (19): 14142–14152. doi:10.1021/acs.jmedchem.1c01290. ISSN 0022-2623. PMID 34606259. S2CID 238355647.

[2] Zhao, Xue; Liu, Hongzhong; Tian, Wei; Fang, Ligang; Yu, Mengyang; Wu, Xiaofei; Liu, Aijing; Wan, Ruijie; Li, Li; Luo, Jinghui; Li, Yuqiong; Liu, Bo; He, Yu; Chen, Xiaowen; Li, Yuan; Xu, Donghong; Wang, Hongyun; Han, Xiaohong (2023). "Safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple doses of aficamten in healthy Chinese participants: a randomized, double-blind, placebo-controlled, phase 1 study". Frontiers in Pharmacology. 14. doi:10.3389/fphar.2023.1227470. PMC 10482267. PMID 37680714.

[3] Sebastian, Sneha Annie; Padda, Inderbir; Lehr, Eric J.; Johal, Gurpreet (September 2023). "Aficamten: A Breakthrough Therapy for Symptomatic Obstructive Hypertrophic Cardiomyopathy". American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions. 23 (5): 519–532. doi:10.1007/s40256-023-00599-0. ISSN 1179-187X. PMID 37526885. S2CID 260348901.

[4] Maron, Martin S.; Masri, Ahmad; Choudhury, Lubna; Olivotto, Iacopo; Saberi, Sara; Wang, Andrew; Garcia-Pavia, Pablo; Lakdawala, Neal K.; Nagueh, Sherif F.; Rader, Florian; Tower-Rader, Albree; Turer, Aslan T.; Coats, Caroline; Fifer, Michael A.; Owens, Anjali; Solomon, Scott D.; Watkins, Hugh; Barriales-Villa, Roberto; Kramer, Christopher M.; Wong, Timothy C.; Paige, Sharon L.; Heitner, Stephen B.; Kupfer, Stuart; Malik, Fady I.; Meng, Lisa; Wohltman, Amy; Abraham, Theodore (January 2023). "Phase 2 Study of Aficamten in Patients With Obstructive Hypertrophic Cardiomyopathy". Journal of the American College of Cardiology. 81 (1): 34–45. doi:10.1016/j.jacc.2022.10.020. hdl:2158/1295661. PMID 36599608. S2CID 255472935.

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