The p160 steroid receptor coactivator (SRC) family, SRC-1/NCOA1, SRC-2/NCOA2/TIF2/GRIP1, and SRC-3/NCOA3/AIB1/RAC3/ACTR/pCIP, interact with nuclear receptors and other transcription factors to drive target gene expression and integrate growth signaling pathways on which cancer cells rely. MCB-613 is a small molecule stimulator of SRC-1, SRC-2, and SRC-3 that has been used to disrupt cancer cell homeostatic dependence on SRCs. MCB-613 can increase the interaction of SRCs with the coactivators CBP and CARM1 and can induce ER stress coupled to the generation of reactive oxygen species. Overactivation of SRCs by 1-7 μM MCB-613 was shown to selectively and dose dependently induce paraptosis in a variety of cancer cells in vitro but not in normal cells. At 20 mg/kg, MCB-613 was also shown to inhibit tumor growth in an MCF-7 breast cancer xenograft model in mice.
