Roniciclib (formerly also known as BAY1000394; BAY-1000394) is a novel, potent and orally bioavailable pan-cyclin dependent kinase (CDK) inhibitor wwith anticancer activity. It inhibits CDK1, CDK2, CDK3, CDK4, CDK7, and CDK9 with IC50 values ranging from 5 to 25 nM. Because it specifically binds to and inhibits the activity of serine/threonine kinases involved in the regulation of cell cycle progression and cellular proliferation, namely CDK1/Cyclin B, CDK2/Cyclin E, CDK4/Cyclin D1, and CDK9/Cyclin T1, it demonstrates its antineoplastic activity. Apoptosis is induced and tumor cell proliferation is inhibited when these kinases are inhibited, which results in cell cycle arrest during the G1/S transition. Presently undergoing phase I clinical trials is BAY 1000394, a novel oral cytotoxic agent. The loss of cell-cycle checkpoint function and increased expression of antiapoptotic proteins resulting from deregulated activity of cyclin-dependent kinases (CDK) has been directly associated with the molecular pathology of cancer. With IC(50) values ranging from 5 to 25 nmol/L, BAY 1000394 suppresses the activity of transcriptional CDKs CDK7 and CDK9 as well as cell-cycle CDKs CDK1, CDK2, CDK3, and CDK4. In a variety of human cancer cell lines, cell proliferation was suppressed at low nanomolar concentrations. The suppression of phosphorylation of the CDK substrates RNA polymerase II, nucleophosmin, and retinoblastoma protein was demonstrated in assays involving cells. Cell-cycle profiles aligned with the suppression of CDK 1, 2, and 4, as demonstrated by cell-cycle block and release tests. BAY 1000394's physicochemical and pharmacokinetic characteristics enable quick absorption and a moderate oral bioavailability. After oral dosage, the substance significantly suppresses the growth of several human tumor xenografts on athymic mice, including models of chemotherapy resistance. Moreover, BAY 1000394 exhibits efficacy greater than additive when paired with etoposide and cisplatin.

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.