Pierre, Fabrice; Chua, Peter C.; O’Brien, Sean E.; Siddiqui-Jain, Adam; Bourbon, Pauline; Haddach, Mustapha; Michaux, Jerome; Nagasawa, Johnny; Schwaebe, Michael K.; Stefan, Eric; Vialettes, Anne; Whitten, Jeffrey P.; Chen, Ta Kung; Darjania, Levan; Stansfield, Ryan; Anderes, Kenna; Bliesath, Josh; Drygin, Denis; Ho, Caroline; Omori, May; Proffitt, Chris; Streiner, Nicole; Trent, Katy; Rice, William G.; Ryckman, David M. published the artcile< 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>, Reference of 53636-56-9, the main research area is naphthyridinecarboxylic acid derivative CX4945 preparation antitumor structure activity; protein kinase CK2 target antitumor CX 4945 preparation.
Herein we chronicle the discovery of CX-4945 (I), a first-in-class, orally bioavailable ATP-competitive inhibitor of protein kinase CK2 in clin. trials for cancer. CK2 has long been considered a prime cancer drug target because of the roles of deregulated and overexpressed CK2 in cancer-promoting pro-survival and antiapoptotic pathways. These biol. properties as well as the suitability of CK2’s small ATP binding site for the design of selective inhibitors, led us to fashion novel therapeutic agents for cancer. The optimization leading to I (Ki = 0.38 nM) was guided by mol. modeling, suggesting a strong binding of I resulting from a combination of hydrophobic interactions, an ionic bridge with Lys68, and hydrogen bonding with the hinge region. I was highly selective, orally bioavailable across species (20-51%) and efficacious in xenograft models. The discovery of I will allow the therapeutic targeting of CK2 in humans for the first time.
Journal of Medicinal Chemistry published new progress about Antitumor agents. 53636-56-9 belongs to class pyridine-derivatives, and the molecular formula is C7H6BrNO2, Reference of 53636-56-9.