XJ-4-85 is a highly selective, covalent, allosteric phosphofructokinase-1 liver type (PFKL) activator with EC50 of 342.3 nM in substrate assays (4h), releases carnitine palmitoyltransferase 2 (CPT2) inhibitor destabilize cancer cell metabolism.
XJ-4-85 selectively modifies K677 in the allosteric effector site to stabilize the R-state tetramer of PFKL.
XJ-4-85 exhibits dose- and time-dependent activation of PFKL.
XJ-4-85 potently engages PFKL in HEK293T cells with IC50 of 141 nM in gel-based competitive ABPP data, but no other detectable PFK1 isoforms.
XJ-4-85 activates glycolysis across multiple cell types, induces rapid alterations in glycolytic metabolism.
XJ-4-85 (5 uM. 2h) markedly elevated intracellular FBP levels in THP-1, Jurkat, MOLM-14 and SH-SY5Y cells relative to vehicle control.
XJ-4-85 releases a selective CPT2-targeting payload, inhibits cell proliferation against B16-F10-Luc2 and MOLM-14 cells with IC50 of ~2 uM.
XJ-4-85 (10-50 mg/kg, intraperitoneal injection) inhibits melanoma tumor outgrowth in C57BL/6 mice bearing B16-F10-Luc2 tumors.