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An Investigation Of The Ck2-Dependent Phosphoproteome Using Inhibitor Refractory Ck2-Alpha, Edward Cruise
An Investigation Of The Ck2-Dependent Phosphoproteome Using Inhibitor Refractory Ck2-Alpha, Edward Cruise
Electronic Thesis and Dissertation Repository
Protein kinase CK2 is a constitutively active serine/threonine kinase that is overexpressed in several human cancers, and by virtue of the vast number of putative substrates in the phosphoproteome, is implicated in the regulation of numerous cellular processes. Consequently, CK2 is an emerging therapeutic target with many CK2 inhibitors having been developed. An example of one such inhibitor is the clinical stage compound CX-4945. Although highly selective for CK2, the ATP competitive CX-4945 has demonstrated affinity for other kinases. Unique features of the catalytic pocket of CK2 have allowed for the development of inhibitor refractory mutants, which have since been …
Quantitative Proteomic Characterization Of Cx-4945, A Clinical Stage Inhibitor Of Protein Kinase Ck2, Adam J. Rabalski
Quantitative Proteomic Characterization Of Cx-4945, A Clinical Stage Inhibitor Of Protein Kinase Ck2, Adam J. Rabalski
Electronic Thesis and Dissertation Repository
Protein phosphorylation is controlled by protein kinases, and represents a critical signaling mechanism involved in the regulation of fundamental biological processes. Furthermore, the aberrant regulation of kinase activity is implicated in diseases such as cancer and has resulted in efforts to target kinases therapeutically. Protein kinase CK2, although frequently considered constitutively active, has emerged as a clinical target on the basis of its altered expression in different types of human cancers and its regulatory participation in multiple biological processes. In fact, CX-4945, a small molecule ATP-competitive inhibitor of CK2 has advanced to clinical trial and has been widely used to …
The Rational Design And Evaluation Of Ck2alpha Mutants Bearing Inhibitor-Refractory Amino Acid Substitutions, Sam Reid Fess
The Rational Design And Evaluation Of Ck2alpha Mutants Bearing Inhibitor-Refractory Amino Acid Substitutions, Sam Reid Fess
Electronic Thesis and Dissertation Repository
CK2 is a ubiquitously expressed and constitutively active serine/threonine protein kinase that is implicated in many cellular functions. Previous studies have indicated that the generation of mutants that are less sensitive to inhibition can be advantageous when studying protein kinases. Importantly, studies have demonstrated that mutants of CK2 rendered less sensitive to inhibition are attainable. To extend these observations, mutants of CK2α were designed and evaluated to test their effect on the inhibition of CK2 by CX-4945 using in vitro enzymatic assays followed by the development of inducible cell lines. CX-4945 is a CK2 inhibitor that has demonstrated anti-tumor activity …