論文 - 詳細
| RRC ID | 19340 |
|---|---|
| 著者 | Uehara Y, Mochizuki M, Matsuno K, Haino T, Asai A. |
| タイトル | Novel high-throughput screening system for identifying STAT3-SH2 antagonists. |
| ジャーナル | Biochem Biophys Res Commun |
| Abstract |
Constitutive activation of the oncogenic transcription factor STAT3 frequently occurs in various human malignancies. STAT3 activation involves dimerization via intermolecular pTyr-SH2 interaction. Thus, antagonizing this interaction is a feasible approach to inhibit STAT3 activation for cancer therapy. In order to identify selective STAT3 inhibitors, we developed a biochemical HTS system based on AlphaScreen technology, which measures the abilities of test compounds to antagonize pTyr-SH2 interactions. We screened our chemical libraries using this system and identified 5,15-diphenylporphyrin (5,15-DPP) as a selective STAT3-SH2 antagonist. Selective inhibition of STAT3 nuclear translocation and DNA biding activity was observed in cells treated with 5,15-DPP. IL-6-dependent dimerization of STAT3, c-myc promoter binding and c-myc protein expression were all suppressed by 5,15-DPP, whereas no decrement in either expression or phosphorylation level of STAT3 was observed. Thus, the HTS assay system represented herein may be useful for identifying novel STAT3-SH2 antagonists. |
| 巻・号 | 380(3) |
| ページ | 627-31 |
| 公開日 | 2009-3-13 |
| DOI | 10.1016/j.bbrc.2009.01.137 |
| PII | S0006-291X(09)00193-4 |
| PMID | 19285012 |
| MeSH | Amino Acid Sequence Antineoplastic Agents / isolation & purification* Antineoplastic Agents / pharmacology Dimerization Drug Screening Assays, Antitumor / methods Humans STAT3 Transcription Factor / antagonists & inhibitors* STAT3 Transcription Factor / metabolism src Homology Domains / drug effects* src-Family Kinases / metabolism* |
| IF | 2.985 |
| 引用数 | 45 |
| WOS 分野 | BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 5 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | 293(RCB1637) |