Oxindole derivatives as inhibitors of TAK1 kinase

Bioorganic and Medicinal Chemistry Letters

Volumn 21, Issue 6, 2011, Pages 1724-1727

  Lockman, Jeffrey W ^a   Reeder, Matthew D ^a   Robinson, Rosann ^a   Ormonde, Patricia A ^a   Cimbora, Daniel M ^a   Williams, Brandi L ^a   Willardsen, J Adam ^a  

^a Myrexis Inc   (United States)

Author keywords

Kinase; Oxindole; TAK1

Indexed keywords

INDOLE DERIVATIVE; OXINDOLE DERIVATIVE; TRANSFORMING GROWTH FACTOR BETA ACTIVATED KINASE 1; UNCLASSIFIED DRUG;

ARTICLE; CONTROLLED STUDY; DRUG CYTOTOXICITY; DRUG POTENCY; DRUG SCREENING; DRUG SYNTHESIS; ENZYME INHIBITION; IC 50; IN VITRO STUDY; STRUCTURE ACTIVITY RELATION;

INDOLES; INHIBITORY CONCENTRATION 50; MAP KINASE KINASE KINASES; PROTEIN KINASE INHIBITORS;

EID: 79952361897     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2011.01.077     Document Type: Article

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13. 1H NMR.
14. 33P filter plate assay using 25 μM ATP and histone H1 as substrate.
15. HeLa cells overexpressing TAK1 and TAB1 were stimulated with TNFα in the absence or presence of TAK1 inhibitors and TAK1 kinase activity was measured by immunoprecipitating TAK1-TAB1 from the cell lysates and performing an in vitro kinase reaction.
16. Cells overexpressing TAK1 and TAB1 were stimulated with TNFα in the absence or presence of TAK1 inhibitors and TAK1 autophosphorylation was measured with an in-cell ELISA assay. Cells were fixed and stained with anti-phospho-TAK1 (T187) antibody followed by HRP-conjugated secondary antibody and HRP activity was measured.