『徳島大学 教育・研究者情報データベース (EDB)』---[学外] /
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EID=338507EID:338507, Map:0, LastModified:2018年7月2日(月) 14:07:21, Operator:[大家 隆弘], Avail:TRUE, Censor:0, Owner:[宇都 義浩], Read:継承, Write:継承, Delete:継承.
種別 (必須): 学術論文 (審査論文) [継承]
言語 (必須): 英語 [継承]
招待 (推奨):
審査 (推奨): Peer Review [継承]
カテゴリ (推奨): 研究 [継承]
共著種別 (推奨): 国際共著 (徳島大学内研究者と国外研究機関所属研究者との共同研究) [継承]
学究種別 (推奨): 博士前期課程学生による研究報告 [継承]
組織 (推奨): 1.徳島大学.大学院社会産業理工学研究部.生物資源産業学域 (2017年4月1日〜) [継承]
著者 (必須): 1. (英) Nguyen Binh Cao Quan (日) (読)
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2. (英) Takahashi Hideaki (日) 髙橋 秀明 (読) たかはし ひであき
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学籍番号 (推奨): **** [ユーザ]
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3.宇都 義浩 ([徳島大学.大学院社会産業理工学研究部.生物資源産業学域.応用生命系.応用生物資源学分野]/[徳島大学.生物資源産業学部.生物資源産業学科.応用生命講座])
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学籍番号 (推奨):
[継承]
4. (英) Shahinozzaman MD (日) (読)
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[継承]
5. (英) Tawata Shinkichi (日) (読)
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[継承]
6. (英) Maruta Hiroshi (日) (読)
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[継承]
題名 (必須): (英) 1,2,3-Triazolyl ester of Ketorolac: A "Click Chemistry"-based highly potent PAK1-blocking cancer-killer.  (日)    [継承]
副題 (任意):
要約 (任意): (英) An old anti-inflammatory/analgesic drug called Toradol is a racemic form of Ketorolac (50% R-form and 50% S-form) that blocks the oncogenic RAC-PAK1-COX-2 (cyclooxygenase-2) signaling, through the direct inhibition of RAC by the R-form and of COX-2 by the S-form, eventually down-regulating the production of prostaglandins. However, due to its COOH moiety which is clearly repulsive to negatively-charged phospholipid-based plasma membrane, its cell-permeability is rather poor (the IC against the growth of human cancer cells such as A549 is around 13 μM). In an attempt to boost its anti-cancer activity, hopefully by increasing its cell-permeability through abolishing the negative charge, yet keeping its water-solubility, here we synthesized a 1,2,3-triazolyl ester of Toradol through "Click Chemistry". The resultant water-soluble "azo" derivative called "15K" was found to be over 500 times more potent than Toradol with the IC around 24 nM against the PAK1-dependent growth of A549 cancer cells, inactivating PAK1 in cell culture with the apparent IC around 65 nM, and inhibiting COX-2 in vitro with the IC around 6 nM. Furthermore, the Click Chemistry boosts the anti-cancer activity of Ketorolac by 5000 times against the PAK1-independent growth of B16F10 melanoma cells. Using a multi-drug-resistant (MDR) cancer cell line (EMT6), we found that the esterization of Ketorolac boosts its cell-permeability by at least 10 folds. Thus, the Click Chemistry dramatically boosts the anti-cancer activity of Ketorolac, at least in three ways: increasing its cell-permeability, the anti-PAK1 activity of R-form and anti-COX-2 activity of S-form. The resultant "15K" is so far among the most potent PAK1-blockers, and therefore would be potentially useful for the therapy of many different PAK1-dependent diseases/disorders such as cancers.  (日)    [継承]
キーワード (推奨): 1. (英) COX-2 (日) (読) [継承]
2. (cancer) [継承]
3. (英) Click chemistry (日) (読) [継承]
4. (英) Ketorolac (日) (読) [継承]
5. (英) PAK1 (日) (読) [継承]
6. (英) Triazole ring (日) (読) [継承]
発行所 (推奨):
誌名 (必須): European Journal of Medicinal Chemistry (French Sociêtê de Chimie Thêrapeutique)
(pISSN: 0223-5234, eISSN: 1768-3254)

ISSN (任意): 1768-3254
ISSN: 0223-5234 (pISSN: 0223-5234, eISSN: 1768-3254)
Title: European journal of medicinal chemistry
Title(ISO): Eur J Med Chem
Publisher: Elsevier BV
 (NLM Catalog  (Scopus  (CrossRef (Scopus information is found. [need login])
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(必須): 126 [継承]
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(必須): 270 276 [継承]
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年月日 (必須): 西暦 2017年 1月 27日 (平成 29年 1月 27日) [継承]
URL (任意):
DOI (任意): 10.1016/j.ejmech.2016.11.038    (→Scopusで検索) [継承]
PMID (任意): 27889630    (→Scopusで検索) [継承]
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Scopus (任意): 2-s2.0-84997522793 [継承]
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被引用数 (任意):
指導教員 (推奨): 1.宇都 義浩 ([徳島大学.大学院社会産業理工学研究部.生物資源産業学域.応用生命系.応用生物資源学分野]/[徳島大学.生物資源産業学部.生物資源産業学科.応用生命講座]) [継承]
備考 (任意): 1.(英) Article.ELocationID: S0223-5234(16)30976-X  (日)    [継承]
2.(英) Article.ELocationID: 10.1016/j.ejmech.2016.11.038  (日)    [継承]
3.(英) Article.PublicationTypeList.PublicationType: Journal Article  (日)    [継承]
4.(英) KeywordList.Keyword: COX-2  (日)    [継承]
5.(英) KeywordList.Keyword: Cancer  (日)    [継承]
6.(英) KeywordList.Keyword: Click chemistry  (日)    [継承]
7.(英) KeywordList.Keyword: Ketorolac  (日)    [継承]
8.(英) KeywordList.Keyword: PAK1  (日)    [継承]
9.(英) KeywordList.Keyword: Triazole ring  (日)    [継承]

標準的な表示

和文冊子 ● Quan Binh Cao Nguyen, Hideaki Takahashi, Yoshihiro Uto, MD Shahinozzaman, Shinkichi Tawata and Hiroshi Maruta : 1,2,3-Triazolyl ester of Ketorolac: A "Click Chemistry"-based highly potent PAK1-blocking cancer-killer., European Journal of Medicinal Chemistry, Vol.126, 270-276, 2017.
欧文冊子 ● Quan Binh Cao Nguyen, Hideaki Takahashi, Yoshihiro Uto, MD Shahinozzaman, Shinkichi Tawata and Hiroshi Maruta : 1,2,3-Triazolyl ester of Ketorolac: A "Click Chemistry"-based highly potent PAK1-blocking cancer-killer., European Journal of Medicinal Chemistry, Vol.126, 270-276, 2017.

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