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

• 영문명: Inhavition of CDK4 activity by 7-chloro-4-nitro-benzo[1,2,5]oxadiazole 1-oxide
• 발행기관: 대한약학회
• 저자명: 전용진(Young Jin Jeon) 고종희(Jong Hee Ko) 연승우(Seung Woo Yeon) 김태용(Tae Yong Kim)
• 간행물 정보: 『약학회지』제50권 제1호 (2006년), 52~57쪽, 전체 6쪽
• 주제분류: 의약학 > 기타의약학
• 파일형태: PDF
• 발행일자: 2006.02.28

영문 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

CDK4 CDK2 cell cycle benzooxadiazole