HDM2-P53 INHIBITOR AND BCL2 INHIBITOR INTERACTION COMBINATIONS AND THEIR USE FOR CANCER TREATMENT Russian patent published in 2023 - IPC A61K31/506 A61K31/635 A61K39/395 A61K45/06 A61P35/00 

FIELD: pharmaceutical chemistry.

SUBSTANCE: use of co-crystal succinic acid: (S)-5-(5-chloro-1-methyl-2-oxo-1,2-dihydro-pyridin-3-yl)-6-(4-chloro-phenyl)-2-(2,4-dimethoxy-pyrimidin-5-yl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-d]imidazol-4-one [HDM201] with a ratio of 1:1 (molar ratio), in the treatment of wild-type acute myeloid leukemia (AML) TP53, wherein the treatment further comprises administering a BCL2 inhibitor, which is 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-[(3-nitro-4-{[(oxan-4-yl)methyl]amino}phenyl)sulfonyl]-2-[(1H-pyrrolo[2,3-b]pyridin-5-yl)oxy]benzamide [venetoclax], where a co-crystal with a succinic acid:HDM201 ratio of 1:1 (molar ratio) is administered on days 1-5 of a 28-day treatment cycle and where a co-crystal with a ratio of succinic acid:HDM201 of 1:1 (molar ratio) is administered at a dose of 20, 30 or 40 mg (expressed as HDM201 free base) on the days of administration, and where venetoclax is administered per daily dose from 300 mg to 600 mg.

EFFECT: treatment of wild-type acute myeloid leukemia (AML) TP53.

15 cl, 9 dwg, 3 tbl, 3 ex