Structure-based design of nitrogen-linked macrocyclic kinase inhibitors leading to the clinical candidate SB1317/TG02, a potent inhibitor of cyclin dependant kinases (CDKs), Janus kinase 2 (JAK2), and Fms-like tyrosine kinase-3 (FLT3)

Journal of Molecular Modeling

Volumn 19, Issue 1, 2013, Pages 119-130

  Poulsen, Anders ^a   William, Anthony ^a   Blanchard, Stéphanie ^a   Nagaraj, Harish ^a   Williams, Meredith ^a   Wang, Haishan ^a   Lee, Angeline ^a   Sun, Eric ^a   Teo, Ee Ling ^a   Tan, Evelyn ^a   Goh, Kee Chuan ^a   Dymock, Brian ^a  

^a S BIO Pte Ltd   (Singapore)

Author keywords

Bioactive conformation; CDK2; Cyclin dependent kinase; Docking; FLT3; Fms related tyrosine kinase; JAK2; Janus kinase 2; Kinase inhibitor; SB1317; Structure based design; Subtype selectivity

Indexed keywords

ANILINE; ANTINEOPLASTIC AGENT; AURORA A KINASE; CD135 ANTIGEN; CYCLIN DEPENDENT KINASE; CYCLIN DEPENDENT KINASE INHIBITOR; JANUS KINASE 2; JANUS KINASE 2 INHIBITOR; PYRIMIDINE; SB 1317; TG 02; UNCLASSIFIED DRUG;

ARTICLE; BINDING SITE; CELL PROLIFERATION; CHEMICAL INTERACTION; COMPETITIVE INHIBITION; CONFORMATION; DENSITY FUNCTIONAL THEORY; DRUG DESIGN; DRUG EFFICACY; DRUG STRUCTURE; HIGH THROUGHPUT SCREENING; HYDROGEN BOND; MOLECULAR DOCKING; MONTE CARLO METHOD; PRIORITY JOURNAL; PROTEIN STRUCTURE; PROTEIN TARGETING; RING CLOSING METATHESIS;

ADENOSINE TRIPHOSPHATE; ANIMALS; BINDING SITES; CYCLIN-DEPENDENT KINASES; DRUG DESIGN; FMS-LIKE TYROSINE KINASE 3; HETEROCYCLIC COMPOUNDS WITH 4 OR MORE RINGS; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; INHIBITORY CONCENTRATION 50; JANUS KINASE 2; MACROCYCLIC COMPOUNDS; MICE; MODELS, MOLECULAR; NITROGEN; PROTEIN KINASE INHIBITORS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84872311254     PISSN: 16102940     EISSN: 09485023     Source Type: Journal    
DOI: 10.1007/s00894-012-1528-7     Document Type: Article

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