SPH3643: A novel cyclin-dependent kinase 4/6 inhibitor with good anticancer efficacy and strong blood-brain barrier permeability.

The cyclin-dependent kinase (CDK)4/6-cyclin D1-Rb-p16/ink4a pathway is responsible for regulating cell progression past the G restriction point during the cell cycle. The development of a majority of human tumors is associated with dysregulation of this pathway, resulting in increased cancer cell proliferation. Both CDK4 and CDK6, well-validated cancer drug targets, function primarily as catalytic enzymes that mediate the phosphorylation of retinoblastoma protein (Rb).

ERα positively regulated DNMT1 expression by binding to the gene promoter region in human breast cancer MCF-7 cells.

Estrogen receptors (ER) are expressed in approximately 65% of human breast cancer. Clinical trials and retrospective analyses showed that ER-positive (ER+) tumors were more vulnerable to development of chemotherapy resistance than ER-negative (ER-) tumors. The underlying mechanism is still to be elucidated.