UM-164

Furthermore, we identified UM164 as a targeted inhibitor of UHRF1 that substantially inhibits P38 protein phosphorylation, downregulates HK2 expression, and reduces lactate production...In summary, our investigation revealed the molecular mechanisms of epigenetic and metabolic reprogramming in relapsed and refractory B-cell acute lymphoblastic leukemia and provides potential targeted therapeutic strategies to improve its inadequate prognosis. The schematic model showed the regulator network of UHRF1-SFRP5-WNT5A-P38 MAPK-HK2 in B-ALL.

UM-164 shows stronger binding to the active sites of Src compared with the conventional Src inhibitor Dasatinib. Furthermore, the in vitro anti-glioma effect mediated by UM-164 was confirmed in a xenograft glioma model. Together, these findings reveal a mechanism by which UM-164 suppresses the malignant phenotypes of glioma cells and might provide a rationale for UM-164-based anti-glioma clinical trials.