SR-4835 is a potent, highly selective and ATP competitive dual inhibitor of CDK12/CDK13 (CDK12: IC50=99 nM, Kd=98 nM; CDK13: Kd=4.9 nM). SR-4835 acts in synergy with DNA-damaging chemotherapy and PARP inhibitors and provokes triple-negative breast cancer (TNBC) cell death.In Vitro: SR-4835 (90 nM; 0.5-48 hours) suppresses ATM and RAD51 protein levels.
SR-4835 inhibits CDK12/CDK13 which triggers intronic polyadenylation site cleavage and suppresses the expression of core DNA damage response proteins.