Ziftomenib
CAS 2134675-36-6
4MOD1F4ENC, KO 539
717.9 g/mol, C33H42F3N9O2S2
APPROVALS 2025, FDA 2025, 11/13/2025, Komzifti
4-methyl-5-[[4-[[2-(methylamino)-6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4-yl]amino]piperidin-1-yl]methyl]-1-[(2S)-2-(4-methylsulfonylpiperazin-1-yl)propyl]indole-2-carbonitrile
To treat adults with relapsed or refractory acute myeloid leukemia with a susceptible nucleophosmin 1 mutation who have no satisfactory alternative treatment options
Ziftomenib, sold under the brand name Komzifti, is an anti-cancer medication used for the treatment of acute myeloid leukemia.[1] Ziftomenib is a menin inhibitor.[1] It is taken by mouth.[1]
Ziftomenib blocks the interaction between two proteins, menin (MEN1) and KMT2A (also known as mixed lineage leukemia protein, MLL).[2][3]
Ziftomenib was approved for medical use in the United States in November 2025.[4][5]
Ziftomenib, also known as KO539, is an orally bioavailable inhibitor of the menin-mixed lineage leukemia (MLL; myeloid/lymphoid leukemia; KMT2A) fusion protein, with potential antineoplastic activity. Upon oral administration, ziftomenib prevents the interaction between the two proteins menin and MLL, and thus the formation of the menin-MLL complex. This reduces the expression of downstream target genes and results in an inhibition of the proliferation of MLL-rearranged leukemic cells. The menin-MLL complex plays a key role in the survival, growth and proliferation of certain kinds of leukemia cells
SYN
syn
WO2022086986
https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2022086986&_cid=P11-MI9OM2-05631-1
above similar not same
pat
WO2020069027
WO2018175746
WO2017161028
WO2018106820
SYN
https://patentscope.wipo.int/search/en/detail.jsf?docId=US239825810&_cid=P20-MI88RV-91969-1
PAT
- Inhibitors of the myst family of lysine acetyl transferasesPublication Number: US-2025051343-A1
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- RNAi agents for inhibiting expression of HIF-2 alpha (EPAS1), compositions thereof, and methods of usePublication Number: US-12221610-B2Grant Date: 2025-02-11
- N-(3-hydroxy-4-piperidinyl)benzamide derivatives and pharmaceutical compositionsPublication Number: NZ-201856-APriority Date: 1981-10-01
- Novel n-(3-hydroxy-4-piperidinyl)benzamide derivativesPublication Number: EP-0076530-B1Priority Date: 1981-10-01Grant Date: 1985-12-11
- Novel N-(3-hydroxy-4-piperidinyl)benzamide derivativesPublication Number: EP-0076530-A2Priority Date: 1981-10-01
- Boron-containing polyphosphonates for the treatment of calcogenic tumorsPublication Number: JP-S5817120-APriority Date: 1981-06-30
- Novel n-aryl-piperazinealkanamidesPublication Number: IE-53465-B1Priority Date: 1981-06-23
- Novel((bis(aryl)methylene)-1-piperidinyl)-alkyl-pyrimidinonesPublication Number: IE-56180-B1Priority Date: 1982-11-01
- Novel ((bis(aryl)methylene)-1-piperidinyl)alkyl-pyrimidinonesPublication Number: EP-0110435-B1Priority Date: 1982-11-01Grant Date: 1989-01-04
- Novel ((bis(aryl)methylene)-1-piperidinyl)alkyl-pyrimidinonesPublication Number: EP-0110435-A1Priority Date: 1982-11-01
- NEW // BIS (ARYL) METHYLENE / -1-PIPERIDINYL / -ALKYL-PyrimidinonesPublication Number: BG-60538-B2Priority Date: 1982-11-01
- Process for preparing n-(3-hydroxy-4-piperidinyl)benzamide derivativesPublication Number: KR-860001584-B1Priority Date: 1982-07-30Grant Date: 1986-10-10
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Medical uses
Ziftomenib is indicated for the treatment of adults with relapsed or refractory acute myeloid leukemia with a susceptible nucleophosmin 1 mutation who have no satisfactory alternative treatment options.[1]
Adverse effects
The US prescribing information includes warnings and precautions for differentiation syndrome, QTc interval prolongation, and embryo-fetal toxicity.[4]
History
Efficacy was evaluated in KO-MEN-001 (NCT04067336), an open-label, single, arm, multi-center trial in 112 adults with relapsed or refractory acute myeloid leukemia with an nucleophosmin 1 mutation identified using next-generation sequencing or polymerase chain reaction.[4] Participants with nucleophosmin 1 mutations, including type A, B, and D mutations and other nucleophosmin 1 mutations likely to result in cytoplasmic localization of the nucleophosmin 1 protein, were enrolled.[4]
The US Food and Drug Administration granted the application for ziftomenib priority review, breakthrough therapy, and orphan drug designations.[4]
Society and culture
Legal status
Ziftomenib was approved for medical use in the United States in November 2025.[6]
Names
Ziftomenib is the international nonproprietary name.[7][8]
Ziftomenib is sold under the brand name Komzifti.[6]
References
- https://kuraoncology.com/wp-content/uploads/prescribinginformation.pdf
- “Ziftomenib”. NCI Cancer Dictionary. National Cancer Institute.
- Rausch J, Dzama MM, Dolgikh N, Stiller HL, Bohl SR, Lahrmann C, et al. (October 2023). “Menin inhibitor ziftomenib (KO-539) synergizes with drugs targeting chromatin regulation or apoptosis and sensitizes acute myeloid leukemia with MLL rearrangement or NPM1 mutation to venetoclax”. Haematologica. 108 (10): 2837–2843. doi:10.3324/haematol.2022.282160. PMC 10543165. PMID 37102614.
- “FDA approves ziftomenib for relapsed or refractory acute myeloid leukemia with a NPM1 mutation”. U.S. Food and Drug Administration (FDA). 13 November 2025. Retrieved 14 November 2025.
This article incorporates text from this source, which is in the public domain. - “Novel Drug Approvals for 2025”. U.S. Food and Drug Administration (FDA). 13 November 2025. Retrieved 14 November 2025.
- “Kura Oncology and Kyowa Kirin Announce FDA Approval of Komzifti (ziftomenib), the First and Only Once-Daily Targeted Therapy for Adults with Relapsed or Refractory NPM1-Mutated Acute Myeloid Leukemia” (Press release). Kura Oncology. 13 November 2025. Retrieved 14 November 2025 – via GlobeNewswire News Room.
- World Health Organization (2022). “International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 87”. WHO Drug Information. 36 (1). hdl:10665/352794.
- World Health Organization (2022). “International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 88”. WHO Drug Information. 36 (3). hdl:10665/363551.
Further reading
- Wang ES, Issa GC, Erba HP, Altman JK, Montesinos P, DeBotton S, et al. (October 2024). “Ziftomenib in relapsed or refractory acute myeloid leukaemia (KOMET-001): a multicentre, open-label, multi-cohort, phase 1 trial”. The Lancet. Oncology. 25 (10): 1310–1324. doi:10.1016/S1470-2045(24)00386-3. PMID 39362248.
External links
- Clinical trial number NCT04067336 for “First in Human Study of Ziftomenib in Relapsed or Refractory Acute Myeloid Leukemia” at ClinicalTrials.gov
| Clinical data | |
|---|---|
| Trade names | Komzifti |
| Other names | KO-539; KO539 |
| AHFS/Drugs.com | Komzifti |
| License data | US DailyMed: Ziftomenib |
| Routes of administration | By mouth |
| Drug class | Antineoplastic |
| ATC code | None |
| Legal status | |
| Legal status | US: ℞-only[1] |
| Identifiers | |
| IUPAC name | |
| CAS Number | 2134675-36-6 |
| PubChem CID | 138497449 |
| IUPHAR/BPS | 11680 |
| DrugBank | DB17171 |
| ChemSpider | 115009296 |
| UNII | 4MOD1F4ENC |
| KEGG | D12419 |
| ChEMBL | ChEMBL5095038 |
| PDB ligand | K5O (PDBe, RCSB PDB) |
| Chemical and physical data | |
| Formula | C33H42F3N9O2S2 |
| Molar mass | 717.88 g·mol−1 |
| 3D model (JSmol) | Interactive image |
| SMILES | |
| InChI | |
////////Ziftomenib, APPROVALS 2025, FDA 2025, 4MOD1F4ENC, Komzifti