CDDD11-8 is a potent, selective, orally bioavailable CDK9 inhibitor with Ki of 8 nM, shows >50-fold selectivity over other CDKs, also inhibits FLT3-ITD with Ki of 13 nM.
CDDD11-8 also inhibits TRKC, FLT3, NUAK1, GLK, MINK, TNIK, and MST1 with Ki of 10 to 46 nM in a panel of 369 human kinases.
CDDD11-8 exhibits potent anti-proliferative effects leukemic cells that harbored the FLT3-ITD mutation and MLL fusions, such as MV4-11 (FLT3ITD/ITD/MLL-AF4) and MOLM-13 (FLT3ITD/WT/MLL-AF9), and those driven by TRK fusions (e.g., MO91) with GI50 values of < 0.1 uM.
CDDD11-8 (1 µM) decreases the level of total RNAP II and tubulin, suppresses the expressions of c-MYC, MCL-1, and XIAP in MV4-11 and MOLM-13 cells.
CDDD11-8 (75 and 125 mg/kg, PO, QD) demonstrates tumor growth inhibition efficacy against MV4-11 tumor xenografts.
CDDD11-8 also has efficacy in TNBC without apparent toxicity to normal tissues.