Bone-targeted 2,6,9-trisubstituted purines: Novel inhibitors of Src tyrosine kinase for the treatment of bone diseases

Bioorganic and Medicinal Chemistry Letters

Volumn 13, Issue 18, 2003, Pages 3067-3070

  Wang, Yihan ^a   Metcalf III, Chester A ^a   Shakespeare, William C ^a   Sundaramoorthi, Raji ^a   Keenan, Terence P ^a   Bohacek, Regine S ^a   Van Schravendijk, Marie Rose ^a   Violette, Shiela M ^a   Narula, Surinder S ^a   Dalgarno, David C ^a   Haraldson, Chad ^a   Keats, Jeffrey ^a   Liou, Shuenn ^a   Mani, Ukti ^a   Pradeepan, Selvi ^a   Ram, Mary ^a   Adams, Susan ^a   Weigele, Manfred ^a   Sawyer, Tomi K ^a  

^a ARIAD PHARMACEUTICALS INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PROTEIN TYROSINE KINASE INHIBITOR; PURINE DERIVATIVE;

ANIMAL CELL; ARTICLE; BONE DISEASE; CONTROLLED STUDY; DRUG DESIGN; DRUG POTENTIATION; DRUG SELECTIVITY; DRUG SYNTHESIS; ENZYME LINKED IMMUNOSORBENT ASSAY; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; NONHUMAN; OSTEOCLAST; RABBIT;

EID: 12444268973     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(03)00648-6     Document Type: Article

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27. 2, 0. 41 mM DTT, pH 7.4) for 1.5 h for complete Y419 phosphorylation/activation. ARIAD Src kinase inhibitors were serially diluted in duplicate in CKB and added to a BSA blocked polystyrene assay plate (Costar). After activation, biotinylated cdc2 substrate peptide (Pierce) was added to the Src, this solution was immediately added to the diluted ARIAD compounds, and the plate was sealed and incubated for 2 h at 37°C. Detection of phosphorylated substrate was accomplished by binding of the biotin labeled substrate to a neutravidin ELISA plate (PIERCE), probing with a mouse anti-phosphospecific HRP labeled antibody (Zymed), HRP development with ABTS solution (Roche), and reading absorbance at 405 nm on a plate reader.
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