KT-333

KT-333 is a molecular glues that degrades STAT3 protein. KT-333 mediates the selective degradation of STAT3 through the ubiquitin-proteasome system by binding to STAT3 protein and E3 ubiquitin ligase von Hippel-Lindau protein (VHL). KT-333 has strong selectivity for STAT3 protein degradation and good antitumor activity. KT-333 can be used in the study of hematologic malignancies such as large granular lymphocytic leukemia (LGL-L), peripheral T-cell lymphoma (PTCL), and cutaneous T-cell lymphoma (CTCL)^[1]. In Vitro: KT-333 (11.8±2.3 nM, 48 h) degrades STAT3 resulted in irreversible growth inhibition of SU-DHL-1 cell line and induces caspase 3/7 activity in the SU-DHL-1 cell line^[1].
KT-333 has a good degradation effect on STAT3 protein, and in cell phenotypic analysis, its GI₅₀ value in multiple ALCL cell lines ranges from 8.1 to 57.4 nM^[1]. In Vivo: KT-333 (5, 10, 15 and 45 mg/kg, iv.; once a week for two weeks) exhibits dose-dependent antitumor activity. Female NOD SCID mice with xenograft tumors of SU-DHL-1 administered with 5 mg/kg achieved 79.9% tumor growth inhibition (TGI), while those administered 10, 15, or 45 mg/kg experienced complete tumor regression, with these effects sustained until the end of the study^[1].
KT-333 (10, 20 and 30 mg/kg, iv.; once a week for two weeks) exhibits dose-dependent antitumor activity. Female NOD SCID mice with xenograft tumors of SUP-M2 administered with 10 mg/kg achieved 83.8% tumor growth inhibition (TGI), while those administered 20 or 30 mg/kg experienced complete tumor regression, with these effects sustained until the end of the study^[1].