Potential new chemotherapy for breast cancer therapy with a novel KSP inhibitor

• Project/Area Number: 15K10074
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: Ohta Yuki 聖マリアンナ医科大学, 医学部, 講師 (60387066)
• Co-Investigator(Kenkyū-buntansha): 武永 美津子 聖マリアンナ医科大学, 医学(系)研究科(研究院), 教授 (10236490) ; 大滝 正訓 聖マリアンナ医科大学, 医学部, 助教 (20612683)
• Co-Investigator(Renkei-kenkyūsha): FUJII Nobutaka 京都大学, 薬学部, 教授 (60109014) ; OISHI Shinya 京都大学, 薬学部, 准教授 (80381739)
• Research Collaborator: TSUCHIYA Seiko ; NIIMI Jun
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: kinesin spindle protein / 乳癌 / 微小管阻害薬 / 末梢神経障害 / KSP

Outline of Final Research Achievements

Among the novel synthetic KSP inhibitors, KPYB 10602 has the highest inhibitory effect on cell proliferation against human breast cancer cell lines, and its effect was highest in MDA-MB-231 cells. The KPYB10602 treatment was shown to result in induction of mitotic arrest with distinct monopolar spindle formation and then apoptotic cell death. KPYB10602 also effectively suppressed tumor growth in a subcutaneous xenograft model. In conclusion, KSP is a good target for breast cancer chemotherapy, and KPYB10602 has a potential as a novel anti-cancer agent for breast cancer.

Research Products

• [Journal Article] A Novel KSP Inhibitor, KPYB10602, Induces Mitotic Arrest and Cell Death in Breast Cancer Cells (2016)
  • Author(s): Kojima-Tsuchiya Seiko, Ohta Yuki, Takenaga Mitsuko, Niimi Jun, Watanabe Daiki, Tsunoda Satoshi, Ootaki Masanori, Oishi Shinya, Fujii Nobutaka, Matsumoto Naoki, Tsugawa Koichiro
  • Journal Title: Journal of St.Marianna University Volume: 7 Pages: 105-116
  • NAID: 130005251535
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 新規KSP阻害薬のヒト乳癌細胞に対する効果 (2018)
  • Author(s): 太田有紀、土屋聖子、武永美津子、新美純、渡邉大輝、大滝正訓、大石真也、藤井信孝、津川浩一郎、松本直樹
  • Organizer: 第138年会日本薬学会
• [Presentation] ヒト乳癌細胞に対する新規KSP(kinesin spindle protein)阻害薬の効果 (2016)
  • Author(s): 太田有紀, 土屋聖子, 武永美津子, 角田智志, 大滝正訓, 新美純, 大石真也, 藤井信孝, 渡辺実, 武半優子, 飯利太朗, 松本直樹
  • Organizer: 第37回日本臨床薬理学会
  • Place of Presentation: 米子コンベンションセンター（鳥取県・米子市）
  • Year and Date: 2016-12-01
• [Presentation] 新規合成KSP(Kinesin spindle protein)阻害剤のヒト乳癌細胞に対する抗腫瘍効果に関する研究 (2016)
  • Author(s): 土屋聖子, 太田有紀, 武永美津子, 大滝正訓, 新美純, 大石真也, 藤井信孝, 松本直樹, 津川浩一郎
  • Organizer: 第24回日本乳癌学会学術総会
  • Place of Presentation: 東京ビッグサイト（東京都・江東区）
  • Year and Date: 2016-06-16
• [Presentation] 癌細胞に対する新規KSP阻害薬の効果 (2015)
  • Author(s): 太田有紀、土屋聖子、武永美津子、大滝正訓、渡辺実、武半優子、飯利太郎、松本直樹
  • Organizer: 第36回日本臨床薬理学会学術総会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2015-12-09