微生物ライブラリーをプラットホームテクノロジーとして、ユニークな医薬品シーズを探索
メンバー： 蓮見惠司、鈴木絵里子
分野： 農芸化学、基礎医学、薬学
所属： 農学研究院
キーワード： 生理活性生化学、細胞生物学
ウェブサイト：
研究概要
微生物のつくる物質のいくつかは、医薬として利用されています。ペニシリンなどの抗生物質がその代表的な例です。地球上には10万種を超える微生物が存在し、多種多様な物質をつくっています。まさに、微生物はユニークな物質の宝庫といえるでしょう。その中には、生命の神秘を解き明かし、また、がん、脳卒中、心筋梗塞、糖尿病など、困難な病気を治す「夢の“くすり”」があるかも知れません。私達はそれを求めて研究を進めています。最近、その１つを医薬開発の軌道に乗せつつあります。
主要論文・参考事項
1) Hasumi K, Yamamichi S, Harada T (2010) Small-molecule modulators of the zymogen activation in the fibrinolytic and coagulation systems. FEBS J 277, 3675-3687.
2) Hashimoto T, Shibata K, Nobe K, Hasumi K, Honda K (2010) A novel embolic model of cerebral infarction and evaluation of SMTP-7, a novel fungal triprenyl phenol metabolite. J Pharmacol Sci 114, 41-49.
3) Shibata K, Hashimoto T, Nobe K, Hasumi K, Honda K (2010) A novel finding of a low-molecular-weight compound, SMTP-7, having thrombolytic and anti-inflammatory effects in cerebral infarction of mice. N-S Arch Pharmacol 382, 245-253.
4) Miyazaki T, Kimura Y, Ohata H, Hashimoto T, Shibata K, Hasumi K, Honda K (2011) Distinct effects of tissue-type plasminogen activator and SMTP-7 on cerebrovascular inflammation following thrombolytic reperfusion. Stroke 42, 1097-1104.
5) Sawada H, Nishimura N, Suzuki E, Zhuang J, Hasegawa K, Takamatsu H, Honda K, Hasumi K (2014) SMTP-7, a novel small-molecule thrombolytic for ischemic stroke: a study in rodents and primates. J Cereb Blood Flow Metab 34, 235-241.
6) Matsumoto N, Suzuki E, Ishikawa M,Shirafuji T, Hasumi K (2014) Soluble epoxide hydrolase as an anti-inflammatorytarget of the thrombolytic stroke drug SMTP-7. J Biol Chem 289, 35826–35838.
お問い合わせ先
東京農工大学・先端産学連携研究推進センター
urac[at]ml.tuat.ac.jp（[at]を@に変換してください）
Bioactive small molecules from microbes: isolation, biochemical characterization, pharmacology, and drug development
Research members： Dr. Keiji Hasumi, Dr. Eriko Suzuki
Research fields： Agricultural chemistry, Basic medicine, Pharmacy
Departments： Institute of Agriculture
Keywords： biological chemistry, bioactive compounds, chemical biology, drug development
Web site：
Summary
SMTPsare a family of novel small molecules derived from a fungus. SMTP enhancesproteolytic activation of plasminogen, a circulating zymogen of plasmin that isresponsible for blood clot dissolution. This activity is attributable to themodulation of plasminogen conformation—while a spiral, closed conformation ofplasminogen resists its proteolytic activation, SMTP relaxes it to anactivation-prone conformation, thus promoting physiological plasmin formationand clot clearance. SMTP is effective in treating thrombotic and embolicstrokes in animal models in rodents and primates. Notably, its action isaccompanied by a reduced hemorrhagic transformation and a wide therapeutic timewindow. The excellent efficacy is partly explained by the anti-inflammatory andantioxidative activities. Based on these properties, we are developing TMS-007,a potent SMTP congener, as a drug for treatment of stroke. TMS-007 is under arandomized, double-blinded, placebo-controlled phase I clinical study.
Reference articles and patents
1) Hasumi K, Yamamichi S, Harada T (2010) Small-molecule modulators of the zymogen activation in the fibrinolytic and coagulation systems. FEBS J 277, 3675-3687.
2) Hashimoto T, Shibata K, Nobe K, Hasumi K, Honda K (2010) A novel embolic model of cerebral infarction and evaluation of SMTP-7, a novel fungal triprenyl phenol metabolite. J Pharmacol Sci 114, 41-49.
3) Shibata K, Hashimoto T, Nobe K, Hasumi K, Honda K (2010) A novel finding of a low-molecular-weight compound, SMTP-7, having thrombolytic and anti-inflammatory effects in cerebral infarction of mice. N-S Arch Pharmacol 382, 245-253.
4) Miyazaki T, Kimura Y, Ohata H, Hashimoto T, Shibata K, Hasumi K, Honda K (2011) Distinct effects of tissue-type plasminogen activator and SMTP-7 on cerebrovascular inflammation following thrombolytic reperfusion. Stroke 42, 1097-1104.
5) Sawada H, Nishimura N, Suzuki E, Zhuang J, Hasegawa K, Takamatsu H, Honda K, Hasumi K (2014) SMTP-7, a novel small-molecule thrombolytic for ischemic stroke: a study in rodents and primates. J Cereb Blood Flow Metab 34, 235-241.
6) Matsumoto N, Suzuki E, Ishikawa M,Shirafuji T, Hasumi K (2014) Soluble epoxide hydrolase as an anti-inflammatorytarget of the thrombolytic stroke drug SMTP-7. J Biol Chem 289, 35826–35838.
Contact
University Research Administration Center(URAC),
Tokyo University of Agriculture andTechnology
urac[at]ml.tuat.ac.jp
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