GW296115 is a potent inhibitor of brain-specific serine/threonine protein kinases BRSK2 with IC50 of 8.4 nM and 21 nM for BRSK2 and BRSK1 respectively.
GW296115 also inhibits DRAK2 (IC50 = 5.5 nM), PHKG1 (IC50 = 20 nM),, DRAK1 (IC50 = 28 nM), and DCAMKL3 (IC50 = 89 nM).
GW296115 engages BRSK2 in cells with an IC50 of 107 nM.
GW296115 also is an inhibitor of platelet-derived growth factor receptor-β (PDGFRβ), inhibits the autophosphorylation of the cytoplasmic domain of PDGFR both in vitro (IC50 = 1.8 uM) and in insect cells (IC50 = 2.0 uM).
GW296115 (1 uM) does not impact cell growth when profiled against 60 cancer cell lines.
GW296115 downregulates BRSK2-driven phosphorylation and downstream signaling.
GW296115 markedly reduces nutrient-deprivation stress-mediated autophagy, cell growth, and metastatic potential, and enhanced breast cancer cell apoptosis.
BRSK2, a marker of aggressive metastatic disease in breast cancer patients, is crucial in regulating autophagy.