5,649 research outputs found
Abstract 3233: Design and synthesis of BPR1K653 and its derivatives targeting the back pocket of Aurora kinases for selective isoform inhibition
No full textAbstract
Guided by computational modeling addressing the back pocket of Aurora kinases, several novel chemical analogs of BPR1K653 were designed and synthesized in two steps with 30-66% yields. All synthesized compounds were evaluated by Aurora-A and Aurora-B enzymatic kinase activity assays, cellular phosphorylation inhibition assays and cell viability assays. Of them, compound 3a that exhibits no substitution at phenylurea showed similar inhibition activity to Aurora-A and -B. Compounds 3b and 3c which harbor tertiary amino group at meta position of phenylurea showed 10-15 fold inhibition selectivity for Aurora-A over Aurora-B in enzymatic assays. In addition, 3b and 3c were more than 200 fold superior in inhibiting T-loop autophosphorylation of Aurora-A compared to Aurora-B in HCT116 colon carcinoma cells. On the other hand, compound 3d with a 4-hydroxypiperidinyl group at ortho position preserves Aurora-B inhibition activity. Molecular docking study revealed that the various steric interaction between the compound and residues in the back pocket of Aurora kinases determines their inhibition selectivity.
Citation Format: Ya-Hui Chi, Chun-Ping Chang, Yi-Yu Ke, Wen-Hsing Lin, Hsing-Pang Hsieh. Design and synthesis of BPR1K653 and its derivatives targeting the back pocket of Aurora kinases for selective isoform inhibition [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3233. doi:10.1158/1538-7445.AM2017-3233</jats:p
Genetic studies on the Wx gene of sorghum[ Sorghum bicolor(L.) Moench] V. Examination of the activity of Wx protein in developing endosperm
No full textDirect solid-phase synthesis of octreotide conjugates: precursors for use as tumor-targeted radiopharmaceuticals
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Beyond Lesson Studies and Design Experiments: Using theoretical tools in practice and finding out how they work
Full text linkThis paper aims to illustrate how fruitful insights into the link between school teaching practice and student learning outcomes can be theoretically grounded by the variation theory from the field of phenomenography; and from this framework demonstrate how a 'pedagogy of awareness' can be implemented in the classroom. In this study, five teachers and 162 students at Primary Four level of school education in Hong Kong participated and the practice of the 'learning study' was adopted. By comparing the results of pre- and posttests, a significant gain was observed in the students learning outcomes.
Facile solid phase synthesis of octreotide analogs using p-carboxybenzaldehyde as a novel linker to anchor Fmoc-threoninol to solid phase resins
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Amorphous ZnO Transparent Thin-Film Transistors Fabricated by Fully Lithographic and Etching Processes
No full textEditorial Overview of the Special Issue “Biological Activity Evaluation Process of Natural Antioxidants”
No full textWe are glad to share the editorial summary of the Special Issue on "Biological Activity Evaluation Process of Natural Antioxidants," edited by Chang-Wei Hsieh and Jer-An Lin of National Chung Hsing University [...
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