In January 2017, it was granted orphan drug status by the U.S. Food and Drug Administration for advanced cholangiocarcinoma. It is being developed by Senhwa Biosciences of Taiwan.[5]
In SARS-CoV-2 (COVID-19) infected Caco-2 cells, the phosphorylase activity of casein kinase 2 (CK2) is increased resulting in phosphorylation of several cytoskeletal proteins. These infected cells also display CK2-containing filopodia protrusions associated with budding viral particles. Hence the protrusions may assist the virus in infecting adjacent cells. In these same cells, the CK2 inhibitor silmitasertib displayed potent antiviral activity.[8] Senhwa Biosciences and the US National Institutes of Health have announced that they will evaluate the efficacy of silmitasertib in treating COVID-19 infections.[9]
History
CX-4945 was originated by now-defunct Cylene Pharmaceuticals of San Diego, California, as the culmination of a lengthy process of rational, structure-basedmolecular modification of a lead compound known to have PARP inhibitor activity.[10] Among a large series of compounds built around a benzo[c]-[2,6]naphthyridine-8-carboxylic acid scaffold, CX-4945 was chosen for its high potency and selectivity as an inhibitor of CK2.[10]
Preclinical pharmacokinetics studies conducted in mice, rats, and dogs confirmed that CX-4945 had satisfactory bioavailability when given by mouth and did not block cytochrome P450, while experiments in mice confirmed its inhibition of solid-tumor growth in a dose-dependent manner.[7][10]
^Lacey E (31 October 2022). "Owner". American Life Fund. Retrieved 19 December 2022.
^Clinical trial number NCT03904862 for "PBTC-053: A Pediatric Brain Tumor Consortium Phase I/ II and Surgical Study of CX-4945 in Patients With Recurrent SHH Medulloblastoma" at ClinicalTrials.gov
^Gowda C, Sachdev M, Muthusami S, Kapadia M, Petrovic-Dovat L, Hartman M, et al. (2017). "Casein Kinase II (CK2) as a Therapeutic Target for Hematological Malignancies". Current Pharmaceutical Design. 23 (1): 95–107. doi:10.2174/1381612822666161006154311. PMID27719640.
^ abcdPierre F, Chua PC, O'Brien SE, Siddiqui-Jain A, Bourbon P, Haddach M, et al. (January 2011). "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". Journal of Medicinal Chemistry. 54 (2): 635–654. doi:10.1021/jm101251q. PMID21174434.
