HTH-02-006 is a potent, selective reversible inhibitor of NUAK1/2 with binding IC50 of 8/126 nM, respectively.HTH-02-006 reduces MYPT1(S445) phosphorylation in HuCCT-1 cells, suggesting NUAK1/2 inhibition.HTH-02-006 ameliorates YAP(S127A)-induced hepatomegaly, and reduces MYPT1(S445) phosphorylation.HTH-02-006 delays the outgrowth of YAP-induced HuCCT-1 xenograft tumors in nude mice.HTH-02-006 downregulated E2F, EMT, and MYC hallmark gene sets after NUAK2 inhibition in PC cells.HTH-02-006 slowed tumor growth and proliferation rates in a syngeneic allograft model and in radical prostatectomy patient derived explants.HTH-02-006 treatment led to inactivation of YAP and the downregulation of NUAK2 and MYC protein levels.
