Ziftomenib

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

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 4-Methyl-5-{{#parsoidfragment:6}}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
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 CC1=C(C=CC2=C1C=C(N2C[C@H](C)N3CCN(CC3)S(=O)(=O)C)C#N)CN4CCC(CC4)NC5=C6C=C(SC6=NC(=N5)NC)CC(F)(F)F
InChI InChI=1S/C33H42F3N9O2S2/c1-21(43-11-13-44(14-12-43)49(4,46)47)19-45-25(18-37)15-27-22(2)23(5-6-29(27)45)20-42-9-7-24(8-10-42)39-30-28-16-26(17-33(34,35)36)48-31(28)41-32(38-3)40-30/h5-6,15-16,21,24H,7-14,17,19-20H2,1-4H3,(H2,38,39,40,41)/t21-/m0/s1 Key:BGGALFIXXQOTPY-NRFANRHFSA-N

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]

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]