UNC1666

UNC1666 is an ATP-competitive dual-target Mer/Flt3 tyrosine kinase inhibitor with IC₅₀ values of 0.55 nM and 0.69 nM, and K_i values of 0.16 nM and 0.67 nM, respectively. UNC1666 reduces the phosphorylation levels of Mer and Flt3, suppresses downstream pro-survival signaling pathways (Erk1/2, Akt and Stat), induces cell apoptosis, and decreases colony formation of acute myeloid leukemia cells. UNC1666 is applicable to research related to acute myeloid leukemia^[1][2]. In Vitro:UNC1666 (Analogue 2) exhibits subnanomolar to low nanomolar in vitro inhibitory activity against Mer, Flt3, Axl (29 nM) and Tyro3 (37 nM) kinases, with the most potent activity against Flt3 (0.69 nM) and Mer (0.93 nM)^[1].
UNC1666 (10-300 nM) inhibits Mer phosphorylation in Kasumi-1 AML cells in a concentration-dependent manner, and potently suppresses Flt3 phosphorylation in MV4;11 Flt3-ITD AML cells^[2].
UNC1666 (50-300 nM) dose-dependently inhibits the downstream pro-survival signaling pathways (Erk1/2, Akt, and Stat) in Mer-positive Kasumi-1 cells and Flt3-ITD MV4;11 AML cells following 2 h of treatment, with stronger activity observed in Flt3-ITD cells^[2].
UNC1666 (10-300 nM; 72 h) induces apoptosis in Mer-positive and Flt3-^ITD AML cell lines in a dose-dependent manner after 72 hours of treatment^[2].
UNC1666 (50-300 nM; 72 h) inhibits the long-term rebound growth of Kasumi-1 and MV4;11 acute myeloid leukemia (AML) cells even after the completion of treatment^[2].
UNC1666 (10-300 nM; 72 h) significantly reduces the colony-forming ability of Mer-positive and Flt3-^ITD AML cell lines cultured in soft agar^[2].
UNC1666 (50-300 nM; 2 h) dose-dependently inhibits the phosphorylation of Mer and Flt3 in primary AML blasts co-expressing Mer and Flt3^ITD, suppresses downstream pro-survival signaling pathways (Erk1/2, Akt, Stat5) in the cells, induces cellular apoptosis, and reduces colony-forming ability^[2].