COMBINATION THERAPY OF CDK7 INHIBITOR BS-181 AND DEATH RECEPTOR LIGAND TRAIL FOR PREVENTION OR TREATMENT OF CANCER

摘要

The present invention relates to a medical use for the prevention or treatment of cancer through a co-administration of a BS-181 compound of chemical formula I, which is a cyclin-dependent kinase 7 (CDK7) inhibitor, and a tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which is a death receptor ligand. According to the present invention, the co-treatment of BS-181 and rTRAIL for a medical use in the prevention or treatment of cancer exhibited a synergistic effect in significantly increasing the cytotoxicity of BS-181 to malignant tumor cells (Jurkat A3, U937, and HeLa) while having no impact on normal human T cells. In particular, the co-treatment of rTRAIL (1-4 ng/ml) and BS-181 was shown to be able to lower the IC_(50) value of BS-181 with respect to Jurkat A3 to a concentration that does not show cytotoxicity to normal T cells, by increasing extrinsic apoptosis induction. These results show that the combination of BS-181 and rTRAIL could be beneficially applied to the treatment of cancer, and in particular, to the treatment of T-ALL.