YN11

YN11 is a STAT3 inhibitor with a dissociation constant (Kd) of 11.9 μM. It directly binds to the SH2 domain of STAT3, suppressing its phosphorylation and reducing the expression of downstream target proteins. YN11 induces cell cycle arrest, promotes apoptosis, and inhibits invasion and migration in prostate cancer cells. It also suppresses tumor growth in xenograft mouse models of prostate cancer without causing significant weight loss or prominent histopathological changes in major organs. YN11 is valuable for research related to prostate cancer.

STAT3:11.9 μM (Ki)

YN11 inhibits STAT3-mediated transcriptional activity in IL-6 stimulated HEK293T cells with an IC50 of 0.17 μM after 24 hours. It suppresses the proliferation of DU145 and 22RV1 prostate cancer cells with IC50 values of 23 nM and 389 nM, respectively, demonstrating high selectivity for cancer cells over normal BEAS-2B cells, with an SI of 82. YN11, in concentrations ranging from 0.01-0.1 μM for DU145 and 0.1-1 μM for 22RV1 over 24 hours, inhibits phosphorylation of STAT3 in a dose-dependent manner without altering total STAT3 levels, while also downregulating downstream targets Bcl-2 and Cyclin D1, showing specificity for STAT3 over STAT1 and STAT5. Furthermore, YN11 induces S-phase cell cycle arrest in DU145 cells and G2/M phase arrest and apoptosis in 22RV1 cells, in a dose-dependent manner. After 24 hours of initial treatment followed by 24 hours of invasion incubation, YN11 dose-dependently inhibits the invasion of DU145 and 22RV1 prostate cancer cells.

In a DU145 prostate cancer xenograft model, YN11 administered via intraperitoneal injection at 20 mg/kg every two days over a span of 17 days achieved a 50.60% tumor growth inhibition rate. It effectively suppressed the STAT3 signaling pathway in tumor tissues without any detectable toxicity.