3,4-Disubstituted isothiazoles: Novel potent inhibitors of VEGF receptors 1 and 2

Bioorganic and Medicinal Chemistry Letters

Volumn 19, Issue 4, 2009, Pages 1195-1198

  Kiselyov, Alexander S ^a   Semenova, Marina ^b   Semenov, Victor V ^c  

^a DeCODE Chemistry & Biostructures   (United States)

^b KOL TSOV INSTITUTE OF DEVELOPMENTAL BIOLOGY   (Russian Federation)

^c N D ZELINSKY INSTITUTE OF ORGANIC CHEMISTRY   (Russian Federation)

Author keywords

Angiogenesis; ATP competitive kinase inhibitors; Isothiazoles; Vascular endothelial growth factor receptor 2; VEGFR 2

Indexed keywords

AMIDE; BAY 579352; ISOTHIAZOLE DERIVATIVE; MOTESANIB; PHOSPHOTRANSFERASE INHIBITOR; UNCLASSIFIED DRUG; VASCULOTROPIN RECEPTOR 1; VASCULOTROPIN RECEPTOR 2; VATALANIB;

ANGIOGENESIS; ANIMAL CELL; ARTICLE; CELL MEMBRANE PERMEABILITY; CELL STRAIN CACO 2; COMPETITIVE INHIBITION; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG SYNTHESIS; ENZYME ACTIVITY; ENZYME LINKED IMMUNOSORBENT ASSAY; ENZYME SPECIFICITY; HUMAN; HUMAN CELL; IN VITRO STUDY; MONOLAYER CULTURE; NONHUMAN; PROTEIN PHOSPHORYLATION; QUALITY CONTROL; SIGNAL TRANSDUCTION;

ADENOSINE TRIPHOSPHATE; CACO-2 CELLS; COMBINATORIAL CHEMISTRY TECHNIQUES; DRUG DESIGN; HUMANS; INDOLES; MOLECULAR STRUCTURE; NIACINAMIDE; PHTHALAZINES; PYRIDINES; STRUCTURE-ACTIVITY RELATIONSHIP; THIAZOLES; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-1; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-2;

EID: 59649112339     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2008.12.078     Document Type: Article

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24. 2, 2 mM DTT, 1 mg/ml BSA) containing 0.5 mmol pGAT-biotin and 3-4 ng KDR enzyme is added to each well. After 5-10 min preincubation, 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 addition of 50 μl of KF buffer, (50 mM Hepes, pH 7.5, 0.5 M KF, 1 mg/ml BSA) containing 100 mM EDTA and 0.36 μg/ml PY20K (Eu-cryptate labeled anti-phosphotyrosine antibody, CIS bio international) is added and after an additional 2 h incubation at room temperature, the plate is read in a RUBYstar HTRF Reader.
25. 4, absorbance was measured at 450 nm.