In vitro
VX-745,a lead anti-inflammatory candidate, is a small-molecule inhibitor of mitogen-activated protein kinase (MAPK). VX-745 inhibits interleukin 6 (IL-6) and vascular endothelial growth factor (VEGF) secretion in bone marrow stromal cells (BMSCs), without affecting their viability. VX-745 can also inhibit tumor necrosis factor alpha (TNF-alpha)-induced IL-6 secretion in BMSCs. VX-745 inhibits both MM cell proliferation and IL-6 secretion in BMSCs triggered by adherence of MM cells to BMSCs. VX-745 can inhibit paracrine MM cell growth in the BM milieu and overcome cell adhesion-related drug resistance. VX-745 potently inhibited TNF release from LPS stimulated human THP-1 cells with IC50s of 29 nM.
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