dCDK9-202

Potency assay, off target (cells): dCDK9-202 was evaluated for its target selectivity in the TC-71 cell line. Among CDKs, compound dCDK9-202 induced the degradation of CDK9 with high selectivity within 8 h. In addition, compound dCDK9-202 did not induce acute depletion of IKZF1/3, which are known off-targets of CRBN E3 ligands as molecular glues. The downregulation of CDK4/5/6/8/11 and IKZF3 was observed after 12 h treatment with dCDK9-202, suggesting a secondary effect.

Potency assay, off target (cells): dCDK9-202 was highly potent and effective in the inhibition of multiple cancer cell lines and achieved IC50 values of 40.9 nM in the T778 cell line (liposarcoma), 83.3 nM in the A-375 cell line (melanoma), 85.3 nM in the MES-SA cell line (uterine sarcoma), 79.6 nM in the MDA-MB-231 cell line (breast cancer), 75.4 nM in the A-673 cell line (Ewing sarcoma), 57.0 nM in the NCI-H226 cell line (lung cancer), 23.4 nM in the NALM6 cell line (B cell acute lymphoblastic leukemia), 174.2 nM in the SJSA-1 cell line (osteosarcoma), 33.9 nM in the U87 cell line (glioblastoma), 106.3 nM in the SKUT1 cell line (uterine leiomyosarcoma), 2.4 nM in the RH5 cell line (rhabdomyosarcoma), and 6.6 nM in the REH cell line (acute lymphocytic leukemia).