Merck, SML2017-25MG, Compound C108

Biochem/physiol Actions
C108 is a small molecule that exhibits cancer-selective cytotoxicity (Viability = 100%/MCF-10A vs. 50%/BT-474, 67%/4T1, 70%/MDA-MB-231 & MDA-MB-453 post 48 h 1 μM C108 treatment) and synergizes with low dose paclitaxel in reducing ALDH-positive tumor-initiating cells (TIC poulation = 56.6%/control, 60.6%/0.1 μM paclitaxel alone, 47.4%/1 μM C108 alone, 7.3%/combined treatment for 24 h in BT474 breast cancer cultures) by targeting stress granule-associated protein G3BP2 (GAP SH3 domain-binding protein 2). Likewise, C108 pretreatment prior to xenografting greatly reduces BT-474 tumor-initiating frequency (from 1/175 to 1/1103 by limiting dilution xenograft assays) in mice in vivo. G3BP2 is reported to bind and stabilize SART3 mRNA, thereby indirectly regulating the core pluripotency transcription factors Oct-4 and Nanog critically involved in ESC self-renewal and breast tumor initiation.
G3BP2 inhibitor that exhibits cancer-selective toxicity and synergizes with low dose paclitaxel against tumor-initiating cell (TIC) population in breast cancer cultures.