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- Title
A NOVEL CDK4/6 INHIBITOR WXJ-111, AGAINST BREAST CANCER THROUGH MEDIATED CELL-CYCLE ARREST AND APOPTOSIS.
- Authors
JING JI; JING FENG; GANG PAN; MING-XIAO LV; JIN-YU LV; WEN-WEN LIU; XING-BEI HE; WEN-LIAN TANG; QI-LAN QIAN; ZHEN ZHANG; YU-XIN XU; MENG-RU XIE; DAN-DAN XIA; YU BAO; XIU-JUN WANG; JIN-MING MA; BIN LIU
- Abstract
Cyclin-dependent kinase (CDKs) are crucial drivers of cell cycle regulation. Aberrations in the CDK-Cyclin-Rb (cyclin-dependent kinase-retinoblastoma protein) pathway are common in cancer (over 90%). A promising therapeutic strategy against cancer involves regulating the CDK4/6-RB pathway. In this research, N1-(5-Fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)-4-methyl-N3-(4-(pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (WXJ-111) as a novel CDK4/6 inhibitor, inhibited the growth activity of MDA-MB-231, MCF-7, A498 and Hela cancer cell lines with IC50 values ranging from 10.88 ± 1.24 to 65.87 ± 6.74 µM, showed significant anti-proliferation, anti-migration and anti-invasion effects on triple-negative breast cancer cells MDA-MB-231. Cell cycle factors such as CDK6, p-Rb, and E2F1 were significantly downregulated. Apoptotic factor Caspase-3 was upregulated, and anti-apoptotic factor Bcl-2 was downregulated. Compound WXJ-111 inhibited MDA-MB-231 cells based on evidence that cell cycle arrest and apoptosis are induced. In summary, the novel CDK4/6 inhibitor compound WXJ-111 may be a promising candidate drug for breast cancer treatment.
- Subjects
CYCLIN-dependent kinases; BREAST cancer treatment; CELL cycle regulation; APOPTOSIS; CASPASES
- Publication
Acta Poloniae Pharmaceutica, 2022, Vol 79, Issue 3, p353
- ISSN
0001-6837
- Publication type
Article
- DOI
10.32383/appdr/152215