梅�一夫教授学术报告会

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报告人：梅�一夫教授    Prof. Umezawa Kazuo

单  位：日本庆应义塾大学  Keio University，Japan

时  间：2008年9月8日，星期一上午9：00

地  点：生命学院二楼会议室

题  目：Screening and anti-inflammatory activities of novel NF-kB inhibitors

新型NF-kB抑制剂的筛选及其抗炎活性

简介:

    梅�一夫（Kazuo Umezawa）教授1969年毕业于东京大学理工学部，1973年获得麻省理工化学系博士学位。Umezawa专攻基础理工和生物化学，研究方向主要涉及癌症、糖尿病、生物活性代谢物、分子组装等。先后在东京大学，东京农工大学，庆应大学等做科学研究工作。1976年获得牛津大学授予的医疗生理学博士学位。1995年庆应大学理工学研究科生体专攻科专攻主任。现任日本庆应大学应用化学研究科化学生物学研究室主任，同时还是美国著名大学布朗大学的访问教授。研究室发表论文200多篇。

摘要：

Many antibiotics, anticancer agents and enzyme inhibitors have been isolated from microorganisms and plants. Therefore, microbial and plant-derived secondary metabolites are a treasury of organic compounds having various structures and biological activities. We have been screening cellular signal transduction inhibitors since 1990. More recently, we are also screening transcription factor inhibitors, chemicals for the regeneration therapy, drugs for SNP, and ligand suppressors.

NF-B is the transcription factor that promotes transcription of inflammatory cytokines, cell adhesion molecules, and inhibitor of apoptosis proteins. Therefore, inhibitors of NF-B functions should be useful as anti-inflammatory and anticancer agents. We have designed dehydroxymethylepoxyquinomicin (DHMEQ) based on the structure of an antibiotic, epoxyquinomicin. DHMEQ inhibited the constitutively activated NF-B in various human neoplastic cells. DHMEQ inhibited the secretion of inflammatory cytokines from cancer cells and macrophages. DHMEQ inhibited the growth of carcinoma and leukemia cells in vivo in which NF-B is constitutively activated. It effectively suppressed prostate carcinoma, thyroid carcinoma, breast carcinoma, pancreatic carcinoma, multiple myeloma, and adult T-cell leukemia in nude or SCID mice without any side effect. It is likely that the anticancer activities are due to the suppression of inflammatory reactions in tumor tissues, since its cytotoxicity is comparatively weak. Recently, we found that DHMEQ directly binds to p65 to inhibit the NF-B functions by SPR and MALDI-TOF-Mass analyses.

We have also discovered novel heptadepsin, 9-methylstreptimidone, and penicillic acid from microorganisms as possible anti-inflammatory agents. Recently we designed and synthesized a novel anti-inflammatory agent derived from the structure of 9-methylstreptimidone. Thus, both chemistry and biology are essential for these screening studies. These bioactive metabolites of low molecular weight can be used for the mechanistic study of diseases without inducing mutation. It is also possible that they may be developed as new chemotherapeutic agents.