LLY17 (Compound 9) is an orally available, potent, and selective STAT3, directly and selectively inhibited the pY705 site of STAT3 with Ki of 400 nM.
LLY17 is highly selective in targeting of cancer cells with IC50 of 0.7 uM against MDA-MB-231, >150 fold selective over MCF-10A normal breast epithelial cells.
LLY17 inhibits multiple types of cancer cells, i.e., the UW426, UW288-1, BKPC3, MDA-MB-231, and U2OS cell lines.
LLY17 directly bound to the STAT3 protein with a Ki value of 2.42 ± 0.26 μM. The ligand:protein molar ratio was determined to be 1:1.
LLY17 selectively inhibited pY705-STAT3 protein. selectively inhibited p-STAT3(Y705) and interleukin 6 (IL-6)-induced phosphorylation of STAT3, without any inhibition of p-STAT1(Y701).
LLY17 induced the expression of STAT3 phosphatase (SHP-1), blocked STAT3 nuclear translocation.
LLY17 (2.5 mg/kg, 5 mg/kg) induced significant antitumor responses in vivo.