FX1-5303 is a highly potent, specific ubiquitin-specific protease 7 (USP7) inhibitor with biochemical IC50 of 0.29 nM.
FX1-5303 displays cellular potency by measuring the p53 accumulation with EC50 of 5.6 nM, inhibition of cell viability with IC50 of 15 nM in MM.1S multiple myeloma (MM) cell line, which is previously shown to be sensitive to USP7 inhibitors.
FX1-5303 is highly selective for USP7, does not inhibit a panel of 44 DUBs.
FX1-5303 (0-3 uM) induces a modest and transient increase of p53 in MRC5 cells.
FX1-5303 demonstrates potent antiproliferative activity in TP53 WT AML cell lines, including MV4-11 and OCI-AML-3, but lacks significant activity in the TP53 mutant HL-60 cell line.
FX1-5303 is synergistic with the BCL2 inhibitor venetoclax.
FX1-5303 (30 mg/kg and 40 mg/kg, BID) efficacious in vivo in mouse cell-line-derived xenograft models of multiple myeloma and acute myeloid leukemia.