In vitro activity: Briciclib (also known as ON 013105 or ON 014185) is an orally bioavailable small molecule and a disodium phosphate ester prodrug of ON 013100 with improved water solubility compared to ON 013100. It a benzyl styryl sulfone derivative that has and potential anticancer activity and can suppresses cyclin D1 accumulation in cancer cells. 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. In summary, in vitro and in vivo data demonstrate the potential of briciclib in targeting eIF4E for hematopoietic and solid cancers and the possibility for developing an oral version of this promising clinical agent.

Kinase Assay: Briciclib is a small molecule that suppresses cyclin D1 accumulation in cancer cells. Target: Cyclin D1 in vitro: 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.

Cell Assay: