Briciclib is a small molecule that suppresses cyclin D1 accumulation in cancer cells.
Briciclib inhibits the proliferation of MCL (JEKO-1 and MINO), breast (MCF7 and MDA-MB-231), gastric (AGS), and esophageal (OE19, OE33, and FLO-1) cancer cell lines at nanomolar concentrations (GI50 = 9.8 - 12.2 nM). Cyclin D1 is a protein required for normal progression through the cell cycle and is overexpressed in many tumors. Cyclin D1 expression is regulated through a process termed cap-dependent translation, which requires the function of eukaryotic initiation factor 4E (eIF4E) protein. In vitro evidence indicates that briciclib binds to eIF4E, blocking cap-dependent translation of cyclin D1 and other cancer proteins (c-MYC, VEGF), leading to tumor cell death. Briciclib is potent and shown to be active in nonclinical tumor models when combined with several chemotherapeutics.