• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Development of a long-acting halogenated HBV capsid inhibitor that is potent against drug-resistant HBV mutants

Research Project

Project/Area Number 20K21609
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 53:Organ-based internal medicine and related fields
Research InstitutionNational Center for Global Health and Medicine

Principal Investigator

Mitsuya Hiroaki  国立研究開発法人国立国際医療研究センター, その他部局等, 研究所長 (20136724)

Project Period (FY) 2020-07-30 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
KeywordsHBV / 慢性B型肝炎 / 薬剤耐性HBV変異株 / HBVキャプシド阻害剤 / 新規抗HBV剤の開発
Outline of Research at the Start

慢性B型肝炎(CHB)の化学療法はヌクレオシト系逆転写酵素阻害剤(NRTIs)の出現で予後の改善を見た。しかし、長期服薬が必要なCHB治療では、薬剤耐性HBVや副作用が問題となり、更に優れた新規抗HBV剤の開発が急務である。HBVキャプシド構成阻害剤(CAIs)はNRTIsとの併用療法の実現で強力な抗HBV効果を発揮すると期待されるが現在開発中のCAIsでは薬剤耐性発現が報告されており、耐性発現を許容しないCAIsの 同定/臨床応用は進んでいない。本研究ではそのようなCAIs耐性HBV変異株にも強力で、耐性発現に抵抗、長時間作用型のハロゲン化CAIsをデザイン・合成・同定し臨床応用を目指す。

Outline of Final Research Achievements

We designed, synthesized, and identified novel HBV capsid composition-inhibiting compounds, and determined 50% inhibitory concentration (IC50) values and 50% cytotoxicity concentration (CC50) values. A compound GRL-07-19 (CC50 = 27 μM, IC50 = 0.007 μM), which has a selectivity index comparable to a previously reported compound/GLS4 (IC50 = 0.015 μM; CC50 = 55 μM), and GRL-12-19 (CC50> 100 μM, IC50 = 0.004 μM) were identified.

Academic Significance and Societal Importance of the Research Achievements

ハロゲン化HBVキャプシド阻害剤候補化合物のデザイン・合成・活性評価で既報化合物GLS4(CC50 =55μM, IC50 =0.015μM),に近い良好な活性を発揮する新規化合物GRL-12-19 (CC50 >100μM, IC50 =0.004μM)を見出した。本化合物は有望なリード化合物になる可能性があり、更なる薬剤開発に重要な情報を提供する点で学術的および社会的意義が高いと考える。

Report

(3 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • Research Products

    (2 results)

All Other

All Int'l Joint Research (2 results)

  • [Int'l Joint Research] Purdue University/NIH(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] NIH/NCI/Purdue University(米国)

    • Related Report
      2020 Research-status Report

URL: 

Published: 2020-08-03   Modified: 2023-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi