CX-4945 . hydrochloride (CAS: 1009820-21-6 (parent))

C₁₉H₁₂ClN₃O₂ . HCl . xH₂O

• Orally active, potent and selective ATP-competitive inhibitor of the protein kinase CK2 (IC₅₀=1nM).
• Anticancer compound. Inhibits proliferation in a panel of cancer cell lines that overexpress CK2. Inhibited migration, blocks survival and induces apoptosis in cancer stem cells, glioblastomas and leukemia cells.
• Shown to decrease the glucose metabolism in cancer cells.
• Potent inhibitor of Cdc2-like kinases (Clks) in vitro, consequently interfering with alternative splicing.
• Potent ATP-competitive inhibitor of DYRK1A (IC₅₀=6.8nM), DYRK1B (IC₅₀=6.4nM) and DYRK3 (IC₅₀=18nM), involved in neurodegeneration-associated diseases.
• CK2α deletion selectively increased M3 muscarinic receptors (M3Rs)-mediated insulin secretion from pancreatic islets.
• Promoted cAMP-induced thermogenesis in white adipocytes.
• CK2 inhibition ameliorates diet-induced obesity and insulin resistance in mice in vivo by promoting UCP1-dependent thermogenesis.

1. CX-4945, an orally bioavailable selective inhibitor of protein kinase CK2, inhibits prosurvival and angiogenic signaling and exhibits antitumor efficacy: A. Siddiqui-Jain, et al.; Cancer Res. 70, 10288 (2010)
2. Structural basis of CX-4945 binding to human protein kinase CK2: A.D. Ferguson, et al.; FEBS Lett. 585, 104 (2011)
3. Discovery and SAR of 5-(3-chlorophenylamino)benzo[c][2,6]naphthyridine-8-carboxylic acid (CX-4945), the first clinical stage inhibitor of protein kinase CK2 for the treatment of cancer: F. Pierre, et al.; J. Med. Chem. 54, 635 (2011)
4. Pre-clinical characterization of CX-4945, a potent and selective small molecule inhibitor of CK2 for the treatment of cancer: F. Pierre, et al.; Mol. Cell Biochem. 356, 37 (2011)
5. CX-4945, a selective inhibitor of casein kinase-2 (CK2), exhibits anti-tumor activity in hematologic malignancies including enhanced activity in chronic lymphocytic leukemia when combined with fludarabine and inhibitors of the B-cell receptor pathway: R.C. Prins, et al.; Leukemia 27, 2094 (2013)
6. CK2 inhibitor CX4945 induces sequential inactivation of proteins in the signaling pathways related with cell migration and suppresses metastasis of A549 human lung cancer cells: M.J. Ku, et al.; Bioorg. Med. Chem. Lett. 23, 5609 (2013)
7. Identification of a novel function of CX-4945 as a splicing regulator: H. Kim, et al.; PLos One 9, e94978 (2014)
8. Activity of the clinical-stage CK2-specific inhibitor CX-4945 against chronic lymphocytic leukemia: L.R. Martins, et al.; Leukemia 28, 179 (2014)
9. Phosphoproteomics identifies CK2 as a negative regulator of beige adipocyte thermogenesis and energy expenditure: K. Shinoda, et al.; Cell Metab. 22, 997 (2015)
10. CK2 acts as a potent negative regulator of receptor-mediated insulin release in vitro and in vivo: M. Rossi, et al.; PNAS 112, E6818 (2015)
11. The casein kinase 2 inhibitor, CX-4945, as an anti-cancer drug in treatment of human hematological malignancies: H.J. Chon, et al.; Front. Pharmacol. 6, 70 (2015)
12. A chemical with proven clinical safety rescues Down-syndrome-related phenotypes in through DYRK1A inhibition: H. Kim, et al.; Dis. Model Mech. 9, 839 (2016)
13. Targeting protein kinase CK2 suppresses bladder cancer cell survival via the glucose metabolic pathway: X. Zhang, et al.; Oncotarget 7, 87361 (2016)