SNX631 (SNX-631) is a potent, selective inhibitor of CDK8/19 Mediator kinase with IC50 of 10.3 nM in the NF κB-dependent cell-based assays.
SNX631 is 6 to 10 times more potent than Senexin B in all the assays except for the DiscoverX activesite-dependent competition binding assay.
SNX631 showed synergistic interactions with lapatinib and trastuzumab in a panel of HER2+ BrCa cell lines, overcoming and preventing resistance to HER2-targeting drugs.
Combination of HER2-mAb trastuzumab and SNX631 inhibited STAT1 and STAT3 phosphorylation at S727 and up-regulated tumor suppressor BTG2 in HER2+ BrCa cell lines.
SNX631 partially inhibits growth of xenograft tumors formed by lapatinib-sensitive or -resistant HER2+ breast cancer cells alone, and strongly suppressed by the combination of lapatinib, overcoming lapatinib resistance.
