dCDK9-202 is a highly potent, selective PROTAC CDK9 degrader with DC50 of 3.5 nM and CDK9 decline (94.4%) at 25 nM in TC-71 cell line, inhibits cell growth with IC50 of 8.5 nM in TC-71 cells.
dCDK9-202 is highly selective in the degradation of CDK9 among the CDK protein family, as well as IKZF.
dCDK9-202 depletes significantly endogenous CDK9 within 25 nM in U87 glioblastoma cells, SKUT1 uterine leiomyosarcoma cells, and RH5 rhabdomyosarcoma cells with DC50 values lower than 10 nM.
dCDK9-202 is capable of inhibiting cell proliferation and inducing apoptosis.
dCDK9-202 exhibits antiproliferative inhibition against multiple cancer cell lines (IC50=40.9 nM for T778 cell line, 79.6 nM for MDA-MB-231 cell line.
dCDK9-202 selectively proteolyzes CDK9 to impair Pol2 function and cancer-addicted transcriptome.
dCDK9-202 (10 mg/kg over a 12 day treatment) significantly inhibited xenograft growth in TC-71 xenograft model in immunocompromised mice.