STAT3-IN-38 (Compound 4m) is a STAT3 inhibitor with a dissociation constant (K_D) of 45.33 µM for rhSTAT3, and is a derivative of Celastrol. It binds to the SH2 domain of the STAT3 protein, inhibiting phosphorylation at the pTyr705 site and suppressing downstream gene expression of Survivin and Mcl-1. STAT3-IN-38 can arrest the cell cycle and induce apoptosis in colorectal cancer cells.

STAT3:45.33 μM (Kd)

STAT3-IN-38 inhibits the phosphorylation of STAT3 in HCT116 cells at concentrations of 0.5-1 μM for 6 hours, and reduces levels of STAT3 target proteins, including survivin and myeloid cell leukemia 1 (Mcl-1). Additionally, STAT3-IN-38 at 0.02-12.5 μM for 48 hours suppresses the proliferation of A549, HCT116, and HepG2 cells. At a concentration of 1-5 μM for 48 hours, it induces apoptosis and cell cycle arrest in HCT116 cells. Moreover, STAT3-IN-38 at 1-10 μM over 6 days decreases the viability of human colorectal cancer organoids (CCOs).