Novel Ribociclib Derivative RB-1 Exhibits Anti-breast Cancer Actions by Regulating p53 and Cell Cycle Pathways

Breast cancer remains the most prevalent malignancy among women globally, with its incidence continuing to rise and ranking as the leading cause of cancer-related mortality in females. Ribociclib, a cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor, suppresses tumor cell proliferation by blocking the transition from the G1 to S phase. This study investigates the molecular mechanisms and therapeutic efficacy of RB-1 (7-cyclopentyl-N-ethyl-N-methyl-2-((3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide), a novel Ribociclib derivative, in inhibiting breast cancer progression. The effects of RB-1 on breast cancer cell viability were evaluated via MTT assay. In vitro and in vivo experiments demonstrated that RB-1 significantly inhibited cell proliferation, colony formation, and the proportion of EdU-positive cells in multiple breast cancer cell lines (e.g., MDA-MB-231 and SKBR3). The chicken chorioallantoic membrane (CAM) assay revealed that RB-1 treatment markedly suppressed tumor angiogenesis, outperforming Ribociclib. Mechanistic studies indicated that RB-1 regulates the p53 signaling pathway and cell cycle-related targets (e.g., E2F targets, mitotic spindle assembly), specifically inhibiting CDK4/6-mediated cell cycle progression. Furthermore, machine learning analysis identified Hyaluronan-Mediated Motility Receptor (HMMR) as a diagnostic and prognostic biomarker for breast cancer, with its expression significantly correlating with tumor-infiltrating immune cells. This study highlights the anti-cancer potential of RB-1 and elucidates its molecular mechanisms, offering a promising therapeutic candidate and novel targets for breast cancer treatment.