Pluripotin is a dual inhibitor of extracellular signal-regulated kinase 1 (ERK1, MAPK3) and RasGAP. It maintains embryonic stem cell (ESC) self-renewal.
Extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) are members of the mitogen-activated protein kinase super family that can mediate cell proliferation and apoptosis[3].
Pluripotin is a dual inhibitor of ERK1 and RasGAP with KDs of 98 nM and 212 nM, respectively. Pluripotin also inhibits RSK1, RSK2, RSK3, and RSK4 with IC50s of 0.5, 2.5, 3.3, and 10.0 µM, respectively[4]. Pluripotin (SC-1) inhibits Abl1, p70S6K, PLK2, RSK1, RSK2, RSK3, RSK4 with IC50s of 0.005, 1.4, 2.2, 0.5, 2.5, 3.3, 10.0 µM, respectively. Pluripotin (SC-1) decreases cell growth for 7 colon tumor cell lines. After a five-day exposure to 0.1 µM SC-1, the seven colon tumor lines are evaluated for changes in cell number and viability. There is a statistically significant decrease in cell number but >95% in viability[5]. Pluripotin significantly promoted the proliferation of RLECs and increased the dividing cells with positive Ki67 staining at the concentrations lower than 400 nM. The colony-forming efficiency increased from 13.5% in the control cells to 26.4% in the 200 or 400 nM pluripotin-treated cells. The number of colonies of moderate size (600-900 μm) increased significantly in the presence of pluripotin (above 60.0% at 200 nM or 400 nM) compared with the untreated normal cells (18.6%), whereas the number of small-sized colonies (<600 μm) decreased from 79.5% for the control cells to lower than 35.0% at 200 nM or 400 nM pluripotin. Moreover, the cells treated with pluripotin stained negative with SA-β-gal, while the untreated cells showed visible positive staining[6].
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