SR-4835

SR-4835 (CAS No.: 2387704-62-1) is a potent, highly selective, ATP-competitive small-molecule inhibitor of cyclin-dependent kinases CDK12 and CDK13, key regulators of transcriptional elongation and DNA damage response pathways. By directly binding to CDK12 and CDK13 with high affinity in the nanomolar range, SR-4835 suppresses kinase-mediated phosphorylation of RNA polymerase II, thereby disrupting transcriptional programs essential for homologous recombination and genomic stability. This mechanism leads to impaired DNA repair capacity and sensitizes cancer cells to genotoxic stress, providing a strong rationale for its use in combination with DNA-damaging chemotherapeutics and PARP inhibitors. In vitro, SR-4835 exhibits robust antiproliferative activity across multiple triple-negative breast cancer cell lines at low nanomolar concentrations and induces DNA damage signaling and apoptosis in susceptible models. In vivo studies further demonstrate its ability to reduce tumor growth in xenograft systems, supporting its relevance in preclinical oncology research. As a targeted transcriptional regulator inhibitor, SR-4835 is widely utilized in studies of transcription-associated kinases, DNA repair dependencies, and combination therapy strategies, with experimental concentrations or dosing regimens typically optimized according to specific cellular or animal model requirements.