Simurosertib

Simurosertib (CAS No.: 1330782-76-7) is a synthetic small-molecule, selective, and ATP-competitive cell division cycle 7 (CDC7) kinase antagonist, specifically used to elucidate key mechanisms of DNA replication initiation and cell-cycle regulation in the context of biomedical research and drug discovery; by inhibiting CDC7-mediated phosphorylation of the replication licensing factor MCM2, it weakens activation of the MCM2-7 helicase, induces replication stress, delays S-phase progression, and triggers G2/S checkpoint arrest, centrosome dysregulation, and chromosome missegregation in susceptible cell lines, thereby producing a research phenotype characterized by inhibited cell proliferation. Enzymatic and cellular evidence indicates that this compound has sub-nanomolar potency against CDC7 and shows significant selectivity over non-homologous kinases; intracellular inhibition of MCM2 phosphorylation is commonly observed at low nanomolar levels, while its antiproliferative activity across multiple tumor-related models spans the nanomolar to high micromolar range, reflecting context-dependent sensitivity associated with genetic background and pathway dependency. As a tool compound, Simurosertib is widely used in in vitro models to validate CDC7 pathway dependency, conduct mechanism-oriented screening and pharmacodynamic readouts, and evaluate target pathway modulation and related biomarker changes in animal xenograft models, supporting basic and pre-translational research on the replication stress and cell-cycle axis; the concentrations or doses used in experiments generally depend on the specific experimental design, model characteristics, and research objectives, and should be optimized accordingly to ensure robust target occupancy and interpretable biomarker responses in the research setting.