title: A novel 2,5-diaminopyrimidine-based affinity probe for Bruton's tyrosine kinase.
abstract: As a critical regulator of the B-cell receptor signaling pathway, Bruton's tyrosine kinase (Btk) has attracted intensive drug discovery efforts for treating B-cell lineage cancers and autoimmune disorders. In particular, covalent inhibitors targeting Cys481 in Btk have demonstrated impressive clinical benefits, and their companion affinity probes have been crucial in the drug development process. Recently, we have discovered a novel series of 2,5-diaminopyrimidine-based covalent irreversible inhibitors of Btk. Here, we present the discovery of a novel affinity Btk probe based on the aforementioned scaffold and demonstrate its usage in evaluating the target engagement of Btk inhibitors in live cells.
authors.affiliation: Key Laboratory of Chemical Genomics, Key Laboratory of Structural Biology, School of Chemical Biology and Biotechnology, Shenzhen Graduate School, Peking University, Shenzhen, China 518055.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Zuo
authors.affiliation: Shenzhen Reciproca Pharmaceuticals Co., Ltd., Xili University Town, Shenzhen, China 518055.
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Key Laboratory of Chemical Genomics, Key Laboratory of Structural Biology, School of Chemical Biology and Biotechnology, Shenzhen Graduate School, Peking University, Shenzhen, China 518055.
authors.forename: Xitao
authors.initials: X
authors.lastname: Li
authors.affiliation: Shenzhen Reciproca Pharmaceuticals Co., Ltd., Xili University Town, Shenzhen, China 518055.
authors.forename: Yingqi
authors.initials: Y
authors.lastname: Teng
authors.affiliation: Key Laboratory of Chemical Genomics, Key Laboratory of Structural Biology, School of Chemical Biology and Biotechnology, Shenzhen Graduate School, Peking University, Shenzhen, China 518055.
authors.forename: Zhengying
authors.initials: Z
authors.lastname: Pan
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D001665:Binding Sites; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D062105:Molecular Docking Simulation; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification; D013329:Structure-Activity Relationship
chemical_list: D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011994:Recombinant Proteins; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; C030986:pyrimidine