약학회지 (YAKHAK HOEJI)

  • 제50권1호
  • /
  • Pages.52-57
  • /
  • 2006
  • /
  • 0377-9556(pISSN)
  • /
  • 2383-9457(eISSN)
대한약학회 (The Pharmaceutical Society of Korea)
권호 표지

7-Chloro-4-nitro-benzo[1,2,5]oxadliazole 1-oxide의 CDK4 활성저해

Inhibition of CDK4 activity by 7-chloro-4-nitro-benzo[1,2,5]oxadiazole 1-oxide

  • 전용진 (일동제약(주) 중앙연구소) ;
  • 고종희 (일동제약(주) 중앙연구소) ;
  • 연승우 (일동제약(주) 중앙연구소) ;
  • 김태용 (일동제약(주) 중앙연구소)
  • Jeon Yong-Jin (Ildong Research Laboratories, Ildong Pharmaceutical Co. Ltd.) ;
  • Ko Jong Hee (Ildong Research Laboratories, Ildong Pharmaceutical Co. Ltd.) ;
  • Yeon Seung Woo (Ildong Research Laboratories, Ildong Pharmaceutical Co. Ltd.) ;
  • Kim Tae-Yong (Ildong Research Laboratories, Ildong Pharmaceutical Co. Ltd.)
  • 발행 : 2006.02.01
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초록

The activation of cyclin dependent kinase 4 (CDK4) is found in more than half of all human cancers. Therefore CDK4 is an attractive target for the development of a novel anticancer agent. For mass screening of CDK4 inhibitor, we set up in vitro kinase assay for CDK4 activity using a cyclin D1-CDK4 fusion protein, which is constitutively active and exhibits enhanced stability. From the screening of representative compound library of Korea Chemical Bank, we found that 7-chloro-4-nitro-benzo[1,2,5]oxadiazole 1-oxide (FBP-1248) selectively inhibited CDK4 activity in vitro by ATP competitive manner. This compound prevented the phosphorylation of retinoblatsoma tumor suppressor protein, Rb, and inhibited cell growth through cell cycle arrest. In summary, we developed an efficient assay system for CDK4 activity in vitro and identified the CDK4 inhibitory compound, FBP-1248.

키워드

참고문헌

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