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Discovery of indirubin derivatives as new class of DRAK2 inhibitors from high throughput screening.
Jung, Myoung Eun; Byun, Byung Jin; Kim, Hye-Mi; Lee, Joo Yun; Park, Jin-Hee; Lee, Nari; Son, You Hwa; Choi, Sang Un; Yang, Kyung-Min; Kim, Seong-Jin; Lee, Kwangho; Kim, Yong-Chul; Choi, Gildon.
Afiliación
  • Jung ME; Drug Discovery Division, Korea Research Institute of Chemical Technology, 141 Gajeong-Ro, Yuseong-gu, Daejeon 305-600, Republic of Korea.
  • Byun BJ; Drug Discovery Division, Korea Research Institute of Chemical Technology, 141 Gajeong-Ro, Yuseong-gu, Daejeon 305-600, Republic of Korea.
  • Kim HM; Drug Discovery Division, Korea Research Institute of Chemical Technology, 141 Gajeong-Ro, Yuseong-gu, Daejeon 305-600, Republic of Korea; Medicinal Chemistry and Pharmacology, Korea University of Science and Technology (UST), 217 Gajeong-Ro, Yuseong-gu, Daejeon 305-350, Republic of Korea.
  • Lee JY; Drug Discovery Division, Korea Research Institute of Chemical Technology, 141 Gajeong-Ro, Yuseong-gu, Daejeon 305-600, Republic of Korea.
  • Park JH; School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
  • Lee N; Drug Discovery Division, Korea Research Institute of Chemical Technology, 141 Gajeong-Ro, Yuseong-gu, Daejeon 305-600, Republic of Korea; Medicinal Chemistry and Pharmacology, Korea University of Science and Technology (UST), 217 Gajeong-Ro, Yuseong-gu, Daejeon 305-350, Republic of Korea.
  • Son YH; Drug Discovery Division, Korea Research Institute of Chemical Technology, 141 Gajeong-Ro, Yuseong-gu, Daejeon 305-600, Republic of Korea.
  • Choi SU; Drug Discovery Division, Korea Research Institute of Chemical Technology, 141 Gajeong-Ro, Yuseong-gu, Daejeon 305-600, Republic of Korea.
  • Yang KM; Department of Biomedical Science, CHA University of Medicine and Science, Kyunggi-do 463-400, Republic of Korea.
  • Kim SJ; Department of Biomedical Science, CHA University of Medicine and Science, Kyunggi-do 463-400, Republic of Korea.
  • Lee K; Drug Discovery Division, Korea Research Institute of Chemical Technology, 141 Gajeong-Ro, Yuseong-gu, Daejeon 305-600, Republic of Korea; Medicinal Chemistry and Pharmacology, Korea University of Science and Technology (UST), 217 Gajeong-Ro, Yuseong-gu, Daejeon 305-350, Republic of Korea.
  • Kim YC; School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea. Electronic address: yongchul@gist.ac.kr.
  • Choi G; Drug Discovery Division, Korea Research Institute of Chemical Technology, 141 Gajeong-Ro, Yuseong-gu, Daejeon 305-600, Republic of Korea; Medicinal Chemistry and Pharmacology, Korea University of Science and Technology (UST), 217 Gajeong-Ro, Yuseong-gu, Daejeon 305-350, Republic of Korea. Electronic
Bioorg Med Chem Lett ; 26(11): 2719-23, 2016 06 01.
Article en En | MEDLINE | ID: mdl-27106709
DRAK2 is a serine/threonine kinase belonging to the death-associated protein kinase (DAPK) family and has emerged as a promising drug target for the treatment of autoimmune diseases and cancers. To identify small molecule inhibitors for DRAK2, we performed a high throughput screening campaign using in-house chemical library and identified indirubin-3'-monoximes as novel class of DRAK2 inhibitors. Among the compounds tested, compound 16 exhibited the most potent inhibitory activity against DRAK2 (IC50=0.003µM). We also propose that compound 16 may bind to the ATP-binding site of the enzyme based on enzyme kinetics and molecular docking studies.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Serina-Treonina Quinasas / Inhibidores de Proteínas Quinasas / Proteínas Reguladoras de la Apoptosis / Descubrimiento de Drogas / Ensayos Analíticos de Alto Rendimiento Tipo de estudio: Diagnostic_studies / Prognostic_studies / Screening_studies Límite: Humans Idioma: En Revista: Bioorg Med Chem Lett Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2016 Tipo del documento: Article Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Serina-Treonina Quinasas / Inhibidores de Proteínas Quinasas / Proteínas Reguladoras de la Apoptosis / Descubrimiento de Drogas / Ensayos Analíticos de Alto Rendimiento Tipo de estudio: Diagnostic_studies / Prognostic_studies / Screening_studies Límite: Humans Idioma: En Revista: Bioorg Med Chem Lett Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2016 Tipo del documento: Article Pais de publicación: Reino Unido