UC-514321

UC-514321 is a more effective analog of NSC-370284 that directly binds to STAT3/5, significantly and selectively suppresses the viability of AML cells with high level of TET1 expression both in vitro and in vivo; shows no inhibitory effect on the viability of TET1-low AML (i.e., NB4) cells, function as TET1-transcription inhibitor in TET1-high AMLs and the anti-leukemic effects are TET1-dependent.

Signaling Pathways >> Stem Cell/Wnt >> STAT

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> JAK/STAT Signaling >> STAT

Research Areas >> Inflammation/Immunology

STAT3

STAT5

UC-514321 increases apoptosis in AML cells not in normal HSPCs[1]. UC-514321 (0-500 nM, 48 h) inhibits AML cells viability TET1-signaling dependently[1]. Cell Viability Assay[1] Cell 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-PCR[1] Cell 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.

UC-514321 (2.5 mg/kg, ip, once per day, for 10 days) exhibits more potant anti-tumor activity than NSC370284 in AML mice models[1]. Animal Model: MLL-AF9-AML mice and AE9a-AML model[1]. 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.

[1]. Jiang X, et al. Targeted inhibition of STAT/TET1 axis as a therapeutic strategy for acute myeloid leukemia. Nat Commun. 2017 Dec 13;8(1):2099.