Development of anticancer drug specifically targeting oncogenic driver mutations

2014 Fiscal Year Final Research Report

• Project/Area Number: 25871150
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical genome science; Tumor therapeutics
• Research Institution: Chiba Cancer Center (Research Institute)
• Principal Investigator: WATANABE Takayoshi 千葉県がんセンター(研究所), がん遺伝創薬研究室, 研究員 (60526060)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: ピロール・イミダゾールポリアミド / KRAS / 変異型ドライバーオンコジーン

Outline of Final Research Achievements

We studied novel anticancer drug candidates using alkylating pyrrole imdazole polyamides (PIP) and CBI conjugates which target several mutant deliver oncogene mutations. Based on a candidate agent, KR12 targeting KRAS codon12 mutant DNA sequence, we synthesized a KR12-α derivative of KR12 which also showed antitumor activities as seen in KR12. In addition, PIP-CBIs targeting variable mutant driver oncogenes other than KRAS were designed and synthesized. As a result, these PIP-CBIs have strong toxicity to cancer lines bearing target mutant mutations, such as ALK, PIK3CA and MYCN.
In conclusion, resulting from the study for two years, great progress of PIP-CBI chemical synthesis has been made and discovered multiple drug candidates which target distinct mutant deriver oncogene DNA mutations.

Free Research Field

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