KT-333 ammonium is a molecular glue that induces the degradation of the STAT3 protein. By binding to STAT3 and the E3 ubiquitin ligase von Hippel-Lindau protein (VHL), KT-333 ammonium leverages the ubiquitin-proteasome system to mediate selective degradation of STAT3. It demonstrates strong selectivity in degrading STAT3 and exhibits significant antitumor activity. KT-333 ammonium can be employed in research on hematologic malignancies such as large granular lymphocyte leukemia (LGL-L), peripheral T-cell lymphoma (PTCL), and cutaneous T-cell lymphoma (CTCL).

KT-333 (11.8±2.3 nM, 48 h) causes irreversible growth inhibition in the SU-DHL-1 cell line by degrading STAT3 and induces caspase 3/7 activity, which is a hallmark of apoptosis [1]. It demonstrates a degrading effect on the STAT3 protein, with GI50 values ranging from 8.1 to 57.4 nM across various ALCL cell lines in cellular phenotypic analyses [1].

KT-333 ammonium, administered intravenously at doses of 5, 10, 15, and 45 mg/kg once a week for two weeks, exhibited dose-dependent antitumor activity. Mice receiving 5 mg/kg achieved 79.9% tumor growth inhibition (TGI), while complete tumor regression was observed in those given 10, 15, or 45 mg/kg, with effects lasting until the end of the study [1]. Similarly, KT-333 ammonium at 10, 20, and 30 mg/kg showed dose-dependent antitumor effects over the same administration schedule. Mice treated with 10 mg/kg exhibited 83.8% TGI, and complete tumor regression was seen at 20 or 30 mg/kg, with sustained effects [1].