Pyrimido-oxazepine as a versatile template for the development of inhibitors of specific kinases

Bioorganic and Medicinal Chemistry Letters

Volumn 15, Issue 24, 2005, Pages 5474-5477

  Pan, Weitao ^a   Liu, Hu ^a   Xu, Yong Jiang ^a   Chen, Xin ^a   Kim, Ki Hwan ^a   Milligan, Daniel L ^a   Columbus, John ^a   Hadari, Yaron R ^a   Kussie, Paul ^a   Wong, Wai C ^a   Labelle, Marc ^a  

^a ELI LILLY AND COMPANY   (United States)

Author keywords

Aurora; FLT 3; Kinase inhibitor; Oxazepine

Indexed keywords

FLT3 LIGAND; OXAZEPINE DERIVATIVE; PHOSPHOTRANSFERASE INHIBITOR; PYRIMIDINONE DERIVATIVE;

ARTICLE; DRUG ACTIVITY; DRUG DESIGN; DRUG SYNTHESIS;

ENZYME INHIBITORS; FMS-LIKE TYROSINE KINASE 3; HUMANS; KINETICS; MODELS, MOLECULAR; OXAZEPINES; PHOSPHOTRANSFERASES; PROTEIN-SERINE-THREONINE KINASES; PYRIMIDINES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 27644549570     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2005.08.098     Document Type: Article

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23. 2, 0.1 mg/ml BSA, and 2 mM DTT) containing 2 nmol pGT-biotin and 5 ng FLT-3 enzyme is added to each well. After 5-10 min pre-incubation, the kinase reaction is initiated by the addition of 10 μl of 10 μM ATP in reaction buffer, after which the plate is incubated at room temperature for 45 min. The reaction is stopped by the addition of 50 μl KF EDTA buffer (50 mM Hepes, pH 7.5, 0.5 M KF, 1 mg/ml BSA, and 100 mM EDTA) containing 0.23 μg/ml PY20K (Eu-cryptate labeled anti-phosphotyrosine antibody, CIS Bio International). After 30 min, 100 μl of 10 nM SV-XL (modified-APC-labeled Streptavidin, CIS Bio International) in KF buffer is added, and after an additional 2-h incubation at room temperature, the plate is read in a RUBYstar HTRF Reader.
24. Unpublished results.