UC-514321, a structural analog of NSC370284 with higher activity, directly targets STAT3/5 and represses TET1 expression, but not TET2 or TET3. UC-514321 has the potential to treat acute myeloid leukemia (AML) both in vitro and in vivo, with low toxicity
In Vitro
UC-514321 increases apoptosis in AML cells not in normal HSPCs. UC-514321 (0-500 nM, 48 h) inhibits AML cells viability TET1-signaling dependently. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Viability AssayCell Line: MONOMAC-6, THP-1, KOCL-48, KASUMI-1, ML-2, and NB4 cells. Concentration: 0-500 nM. Incubation Time: 48 hours. Result: Most significantly repressed MONOMAC-6 cell viability. Showed no inhibitory effect on the viability of TET1-low AML. RT-PCRCell Line: MONOMAC-6 cells. Concentration: 0-500 nM. Incubation Time: 48 hours. Result: Functioned as TET1-transcription inhibitors in TET1-high AMLs and their anti-leukemic effects are TET1-dependent.
In Vivo
UC-514321 (2.5 mg/kg, ip, once per day, for 10 days) exhibits more potent anti-tumor activity than NSC370284 in AML mice models . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: MLL-AF9-AML mice and AE9a-AML model . Dosage: 2.5 mg/kg. Administration: IP., once per day, for 10 days. Result: Showed an improved therapeutic effect in AML mouse models in vivo. Prolonged the median survival over three fold.
