title: 1H-Pyrazolo[3,4-b]pyridine inhibitors of cyclin-dependent kinases.
abstract: 1H-Pyrazolo[3,4-b]pyridine 3 (SQ-67563) has been shown to be a potent, selective inhibitor of CDK1/CDK2 in vitro. In cells 3 acts as a cytotoxic agent with the ability to block cell cycle progression and/or induce apoptosis. The solid state structure of 3 bound to CDK2 shows 3 resides coincident with the ATP purine binding site and forms important H-bonding interactions with Leu83 on the protein backbone.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, PO 4000, Princeton, NJ 08543-4000, USA.
authors.forename: Raj N
authors.initials: RN
authors.lastname: Misra
authors.forename: David B
authors.initials: DB
authors.lastname: Rawlins
authors.forename: Hai-yun
authors.initials: HY
authors.lastname: Xiao
authors.forename: Weifang
authors.initials: W
authors.lastname: Shan
authors.forename: Isia
authors.initials: I
authors.lastname: Bursuker
authors.forename: Kristin A
authors.initials: KA
authors.lastname: Kellar
authors.forename: Janet G
authors.initials: JG
authors.lastname: Mulheron
authors.forename: John S
authors.initials: JS
authors.lastname: Sack
authors.forename: John S
authors.initials: JS
authors.lastname: Tokarski
authors.forename: S David
authors.initials: SD
authors.lastname: Kimball
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Webster
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001681:Biological Assay; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle / Q000187:drug effects; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008968:Molecular Conformation; D010051:Ovarian Neoplasms / Q000188:drug therapy; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: C478081:1H-pyrazolo(3,4-b)pyridine; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases