Multikinase inhibitor 108600 (ON 108600) is a novel multi-kinase inhibitor and inhibitor of TNBC growth (GI50=0.12-0.75 uM), inhibits CK2α1/α2, DYRK1A, 1B, and DYRK2 and TNIK (IC50=5-50 nM).
108600 decreased phosphorylation AKT1 Serine 129, CYCLIN D1 Thr 286 and p27 Ser10 in MDA-MB231 and Hs578T cells, as well as decreased levels of autophosphorylated DYRK1A/B, supressed AXIN2 expression induced by activated Wnt/TCF/LEF.
108600 inhibits viability of TNBC CD44high/CD24low breast cancer stem cells.
108600 binds to CK2α1 and induce a conformational change, which represents a state that is not conducive to holoenzyme formation.
108600 inhibits tubulin polymerization and causes abnormal mitosis in HeLa cells, induces G2/M arrest and apoptosis of TNBC cells and organoids, suppresses the growth of chemotherapy-resistant TNBC cells.
108600 (100 mg/kg) suppresses growth of TNBC cell line and PDX tumor grafts as a single dose or in combination with chemotherapy, synergizes paclitaxel to inhibit established TNBC metastases in vivo.