A NOVEL CDK4/6 INHIBITOR WXJ-111, AGAINST BREAST CANCER THROUGH MEDIATED CELL-CYCLE ARREST AND APOPTOSIS

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 mu M, 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.

Automated summary

Cyclin-dependent kinases (CDKs) play a crucial role in cell cycle regulation. Inhibiting the CDK4/6 pathway with the novel CDK4/6 inhibitor WXJ-111 showed significant anti-proliferative, anti-migratory, and anti-invasive effects on breast cancer cells, as well as downregulation of cell cycle factors and upregulation of apoptotic factors. WXJ-111 may be a promising candidate for breast cancer treatment.