Synthesis of water-soluble Irinotecan bearing symmetrically branched oligoglycerols

• Project/Area Number: 26350502
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biomedical engineering/Biomaterial science and engineering
• Research Institution: The University of Tokushima
• Principal Investigator: NEMOTO Hisao 徳島大学, 大学院医歯薬学研究部(薬学系), 准教授 (30208293)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 癌 / 有機合成 / 水溶性化 / イリノテカン / オリゴグリセロール / 抗癌剤 / 水溶性 / カンプトテシン

Outline of Final Research Achievements

SN38 is a basic skeleton of cancer-suspected agents, a number of derivatives have been developed and studied. A commercially available cancer-suspect agent invented in Japan, "Irinotecan", is one of them, which often have an ammonium cation moiety for their water-solubility. However, non-ionic water-soluble derivatives of SN38 has bot been developed. To design and synthesize such molecules, we examined the covalent bond formation reaction of SN38 and BGL. BGL is a glycerol oligomer, and we have now BGL003 (three glycerol units) and BGL007 (seven glycerol units). The three kinds of hybrid molecule, SN38-BGL, were synthesized. To prepare a practical amount, we developed a new preparation method for BGL, which will be published in patent soon.

Research Products

• [Journal Article] A novel benzofuran, 4-methoxybenzofuran-5-carboxamide, from Tephrosia purpurea suppressed histamine H1 receptor gene expression through a protein kinase C-δ-dependent signaling pathway. (2016)
  • Author(s): Shill MC, Mizuguchi H, Karmakar S, Kadota T, Mukherjee PK, Kashiwada Y, Kitamura Y, Nemoto H, Takeda N, Fukui H.
  • Journal Title: Int Immunopharmacol. Volume: 30 Pages: 18-26
  • DOI: 10.1016/j.intimp.2015.11.021
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Structural analysis of the TKB domain of ubiquitin ligase Cbl-b complexed with its small inhibitory peptide, Cblin (2016)
  • Author(s): Ohno A, Ochi A, Maita N, Ueji T, Bando A, Nakao R, Hirasaka K, Abe T, Teshima-Kondo S, Nemoto H, Okumura Y, Higashibata A, Yano S, Tochio H, Nikawa T
  • Journal Title: Arch Biochem Biophys Volume: 594 Pages: 1-7
  • DOI: 10.1016/j.abb.2016.02.014
  • Peer Reviewed / Open Access / Int'l Joint Research