Aficamten
C18H19N5O2, 337.4 g/mol
FDA 2025, APPROVALS 2025, Myqorzo, 12/19/2025, To treat symptomatic obstructive hypertrophic cardiomyopathy
CK-3773274, B1I77MH6K1, BAY-3723113; CK 3773274; CK 274; MYQORZO
N-[(1R)-5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl]-1-methylpyrazole-4-carboxamide
- (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide
- N-((1R)-5-(5-Ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)- 1-methyl-1H-pyrazole-4-carboxamide
- OriginatorCytokinetics
- DeveloperBayer; Cytokinetics; Sanofi
- ClassAmides; Cardiovascular therapies; Heart failure therapies; Indenes; Oxadiazoles; Pyrazoles; Small molecules
- Mechanism of ActionCardiac myosin inhibitors
- Orphan Drug StatusYes – Hypertrophic cardiomyopathy
- RegisteredHypertrophic cardiomyopathy
- 20 Dec 2025Cytokinetics plans to launch aficamten in the USA in second half of January 2026
- 19 Dec 2025Registered for Hypertrophic cardiomyopathy in USA (PO)
- 19 Dec 2025Aficamten carries a black box warning for the risk of heart failure
Aficamten, sold under the brand name Myqorzo, is a medication used for the treatment of symptomatic obstructive hypertrophic cardiomyopathy.[1] It is a cardiac myosin inhibitor[2] developed by Cytokinetics.[3][4]
Aficamten binds directly to the motor domain of cardiac myosin and prevents it from entering the force-producing state.[5] This lowers cardiac contractility, leading to reduced left ventricular outflow tract obstruction in people with hypertrophic cardiomyopathy.[5]
Aficamten was approved for medical use in the United States in December 2025.[6]
Medical uses
Aficamten is indicated for the treatment of adults with symptomatic obstructive hypertrophic cardiomyopathy to improve functional capacity and symptoms.[1][6]
Symptomatic obstructive hypertrophic cardiomyopathy is an inherited condition where people have thickened heart muscle and reduced blood flow from the left side of the heart to the rest of the body, causing symptoms such as shortness of breath, fatigue, and potentially life-threatening cardiac events.[6]
SYN
https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2019144041&_cid=P10-MJP428-30255-1
Example 15
Synthesis of Compound 184
1. Synthesis of Intermediate 15-2:
[0262] To a solution of tert-butyl N-[(1R)-5-(N-hydroxycarbamimidoyl)-2,3-dihydro-1H-inden-1-yl] carbamate (16 g, 54.9 mmol, 1.0 equiv) in dioxane (300 mL) was added propanoyl propanoate (8.4 g, 64.5 mmol, 1.2 equiv). The mixture was stirred at 105 oC for 8 h, cooled to r.t., concentrated under reduced pressure, and purified by silica gel
chromatography (EA/PE, 1/9) to give 17.5 g (97%) of tert-butyl N-[(1R)-5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl]carbamate as a white solid.
2. Synthesis of Intermediate 15-3:
[0263] To a solution of tert-butyl N-[(1R)-5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl]carbamate (17.6 g, 53.4 mmol, 1.0 equiv) in DCM (120 mL) was added TFA (24 mL). The mixture was stirred at room temperature overnight and concentrated under reduced pressure. The mixture was then poured into ethanol (50 mL) and water (5 mL) and the pH was adjusted to 12 with sodium hydroxide solution (2 N). The mixture was then extracted with dichloromethane (200 mL) three times. The combined organic layers were dried over anhydrous sodium sulfate and concentrated under reduced pressure to give 11.2 g of (1R)-5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-amine as a brown oil. 3. Synthesis of Compound 184:
[0264] To a solution of 1-methyl-1H-pyrazole-4-carboxylic acid (6.1 g, 48.4 mmol, 1.0 equiv) in DMF (300 mL) were added DIEA (12.6 g, 97.5 mmol, 2.0 equiv), HOAt (19.8 g, 145.8 mmol, 3.0 equiv), and EDCI (28 g, 146.1 mmol, 3.0 equiv). The mixture was stirred for 15 min, and (1R)-5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-amine (11.2 g, 48.9 mmol, 1.0 equiv) was then added. The mixture was then stirred for 3 h, diluted with DCM, washed with NH4Cl solution three times, dried over sodium sulfate, concentrated under reduced pressure, and purified by silica gel chromatography (EA/PE, 74/26) to give an intermediate product. The intermediate product was triturated with a mixture of EA and PE (1/10) to afford 14.5 g (88%) of (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide (Compound 184) as a white solid. LRMS (ES) m/z 338 (M+H). 1H-NMR: (DMSO, 300MHz, ppm): į 8.41 (1H, d, J = 8.4 Hz), 8.16 (1H, s), 7.91-7.79 (3H, m), 7.34 (1H, d, J = 7.9 Hz), 5.53 (1H, q, J = 8.3 Hz), 3.84 (3H, s), 3.13-2.81 (4H, m), 2.44 (1H, dd, J = 7.9, 4.7 Hz), 1.95 (1H, m), 1.33 (3H, t, J = 7.5 Hz).
PAT
https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2021011807&_cid=P10-MJP428-30255-1
(R)-N-(5-(5-ethyl- 1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-l-yl)-1-methyl-1H-pyrazole-4-carboxamide,
SYN
https://pubs.acs.org/doi/10.1021/acs.jmedchem.1c01290
PAT
- Cardiac sarcomere inhibitorsPublication Number: US-10836755-B2Priority Date: 2018-01-19Grant Date: 2020-11-17
- Cardiac sarcomere inhibitorsPublication Number: US-12065436-B2Priority Date: 2018-01-19Grant Date: 2024-08-20
- Cardiac sarcomere inhibitorsPublication Number: US-2023119665-A1Priority Date: 2018-01-19
- Cardiac sarcomere inhibitorsPublication Number: US-11472796-B2Priority Date: 2018-01-19Grant Date: 2022-10-18
- Cardiac sarcomere inhibitorsPublication Number: US-2025059173-A1Priority Date: 2018-01-19
- Dihydrobenzofuran and indene analogs as myocardial inhibitorsPublication Number: CN-117964573-APriority Date: 2018-01-19
- Cardiac sarcomere inhibitorsPublication Number: TW-202436291-APriority Date: 2018-01-19
- Dihydrobenzofurans and indene analogs as cardiomyome inhibitorsPublication Number: CN-111757875-BPriority Date: 2018-01-19Grant Date: 2024-01-09
- Dihydrobenzofuran and indene analogs as myocardial inhibitorsPublication Number: CN-117924208-APriority Date: 2018-01-19
- Dihydrobenzofuran and indene analogs as inotropic agentsPublication Number: CN-111757875-APriority Date: 2018-01-19
- Cardiac sarcomere inhibitorsPublication Number: TW-I835770-BPriority Date: 2018-01-19Grant Date: 2024-03-21
- Dihydrobenzofuran and inden analogs as cardiac sarcomere inhibitorsPublication Number: EP-3740481-A1Priority Date: 2018-01-19
- Dihydrobenzofuran and inden analogs as cardiac sarcomere inhibitorsPublication Number: EP-3740481-B9Priority Date: 2018-01-19Grant Date: 2024-10-23
- Cardiac sarcomere inhibitorsPublication Number: US-2021147399-A1Priority Date: 2018-01-19
- Cardiac sarcomere inhibitorsPublication Number: EP-4491622-A2Priority Date: 2018-01-19
REF
- Clinical Evaluation of the Effect of Aficamten on <scp>QT</scp>/<scp>QTc</scp> Interval in Healthy ParticipantsPublication Name: Clinical and Translational SciencePublication Date: 2025-04PMCID: PMC11979292PMID: 40200648DOI: 10.1111/cts.70218
- Effect of Hepatic Impairment or Renal Impairment on the Pharmacokinetics of AficamtenPublication Name: Clinical PharmacokineticsPublication Date: 2025-02-05PMCID: PMC11954688PMID: 39907965DOI: 10.1007/s40262-025-01481-9
- The clinical utility of cardiac myosin inhibitors for the management of hypertrophic cardiomyopathy: a scoping reviewPublication Name: Heart Failure ReviewsPublication Date: 2024-12-17PMCID: PMC11802616PMID: 39690360DOI: 10.1007/s10741-024-10476-w
- Obstructive Hypertrophic Cardiomyopathy: A Review of New TherapiesPublication Name: Future CardiologyPublication Date: 2023-10PMID: 37933625DOI: 10.2217/fca-2023-0056
- Aficamten: A Breakthrough Therapy for Symptomatic Obstructive Hypertrophic CardiomyopathyPublication Name: American journal of cardiovascular drugs : drugs, devices, and other interventionsPublication Date: 2023-08-01PMID: 37526885DOI: 10.1007/s40256-023-00599-0
- Synthesis of AficamtenPublication Name: SynfactsPublication Date: 2021-11-17DOI: 10.1055/s-0041-1737088
- Discovery of Aficamten (CK-274), a Next-Generation Cardiac Myosin Inhibitor for the Treatment of Hypertrophic CardiomyopathyPublication Name: Journal of Medicinal ChemistryPublication Date: 2021-10-04PMID: 34606259DOI: 10.1021/acs.jmedchem.1c01290
- Emerging Medical Treatment for Hypertrophic CardiomyopathyPublication Name: Journal of Clinical MedicinePublication Date: 2021-03-01PMCID: PMC7957690PMID: 33804412DOI: 10.3390/jcm10050951
- Small Molecules Acting on Myofilaments as Treatments for Heart and Skeletal Muscle DiseasesPublication Name: International Journal of Molecular SciencesPublication Date: 2020-12-16PMCID: PMC7767104PMID: 33339418DOI: 10.3390/ijms21249599
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Contraindiations
Use with rifampin is contraindicated.[1]
Adverse effects
The US prescription label for aficamten contains a boxed warning that it reduces left ventricular ejection fraction and can cause heart failure due to systolic dysfunction.[1]
History
The effectiveness and safety of aficamten were studied in 282 adults with symptomatic obstructive hypertrophic cardiomyopathy randomly assigned to receive aficamten or placebo for 24 weeks.[6] At the end of the study, participants receiving aficamten had an increase in exercise capacity measured by peak oxygen uptake compared to no change in exercise capacity among those receiving placebo.[6] Also, 59 percent of participants receiving aficamten experienced an improvement in physical activity limitations (measured using the New York Heart Association Classification system) compared to 24 percent of individuals receiving placebo.[6]
Society and culture
Legal status
Aficamten was approved for medical use in the United States in December 2025.[6][7] The US Food and Drug Administration granted the application for aficamten orphan drug and breakthrough therapy designations.[6]
In December 2025, the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Myqorzo, intended for the treatment of adults with obstructive hypertrophic cardiomyopathy.[5] The applicant for this medicinal product is Cytokinetics (Ireland) Limited.[5]
Names
Aficamten is the international nonproprietary name.[8]
Aficamten is sold under the brand name Myqorzo.[6]
References
- https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/219083s000lbl.pdf [bare URL PDF]
- Chuang, Chihyuan; Collibee, Scott; Ashcraft, Luke; Wang, Wenyue; Vander Wal, Mark; Wang, Xiaolin; et al. (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; et al. (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 1227470. 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.
- “Myqorzo EPAR”. European Medicines Agency (EMA). 12 December 2025. Retrieved 22 December 2025. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
- “FDA approves drug to improve functional capacity and symptoms in adults with rare inherited heart condition”. U.S. Food and Drug Administration (FDA) (Press release). 22 December 2025. Retrieved 22 December 2025.
This article incorporates text from this source, which is in the public domain. - “Cytokinetics Announces FDA Approval of Myqorzo (aficamten) for the Treatment of Adults with Symptomatic Obstructive Hypertrophic Cardiomyopathy to Improve Functional Capacity and Symptoms” (Press release). Cytokinetics. 19 December 2025. Retrieved 22 December 2025 – via GlobeNewswire News Room.
- World Health Organization (2021). “International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 86”. WHO Drug Information. 35 (3). hdl:10665/346562.
Further reading
- Maron, Martin S.; Masri, Ahmad; Choudhury, Lubna; Olivotto, Iacopo; Saberi, Sara; Wang, Andrew; et al. (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.
External links
- Clinical trial number NCT05186818 for “Aficamten vs Placebo in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy (SEQUOIA-HCM) (SEQUOIA-HCM)” at ClinicalTrials.gov
| Clinical data | |
|---|---|
| Trade names | Myqorzo |
| Other names | CK-3773274 |
| License data | US DailyMed: Aficamten |
| Routes of administration | By mouth |
| Drug class | Cardiac myosin inhibitor |
| ATC code | None |
| Legal status | |
| Legal status | US: ℞-only[1] |
| Identifiers | |
| IUPAC name | |
| CAS Number | 2364554-48-1 |
| PubChem CID | 139331495 |
| DrugBank | DB18490 |
| ChemSpider | 114935503 |
| UNII | B1I77MH6K1 |
| KEGG | D12253 |
| ChEMBL | ChEMBL4847050 |
| PDB ligand | 6I6 (PDBe, RCSB PDB) |
| Chemical and physical data | |
| Formula | C18H19N5O2 |
| Molar mass | 337.383 g·mol−1 |
| 3D model (JSmol) | Interactive image |
| SMILES | |
| InChI | |
//////////Aficamten, FDA 2025, APPROVALS 2025, Myqorzo, CK-3773274, CK 3773274, B1I77MH6K1, BAY 3723113; CK 3773274; CK 274, MYQORZO