Discovery of a Potent and Selective Naphthyridine-Based Chemical Probe for Casein Kinase 2.
Basic Information
ID: ALA5252659
Journal: ACS Med Chem Lett
Title: Discovery of a Potent and Selective Naphthyridine-Based Chemical Probe for Casein Kinase 2.
Authors: Davis-Gilbert ZW, Krämer A, Dunford JE, Howell S, Senbabaoglu F, Wells CI, Bashore FM, Havener TM, Smith JL, Hossain MA, Oppermann U, Drewry DH, Axtman AD.
Abstract: Naphthyridine-based inhibitors were synthesized to yield a potent and cell-active inhibitor of casein kinase 2 (CK2). Compound 2 selectively inhibits CK2α and CK2α' when profiled broadly, thereby making it an exquisitely selective chemical probe for CK2. A negative control that is structurally related but lacks a key hinge-binding nitrogen (7) was designed on the basis of structural studies. Compound 7 does not bind CK2α or CK2α' in cells and demonstrates excellent kinome-wide selectivity. Differential anticancer activity was observed when compound 2 was profiled alongside a structurally distinct CK2 chemical probe: SGC-CK2-1. This naphthyridine-based chemical probe (2) represents one of the best available small molecule tools with which to interrogate biology mediated by CK2.
CiteXplore: 37077385
DOI: 10.1021/acsmedchemlett.2c00530
Patent ID: ┄