Description
SJB2-043 is a potent USP1 inhibitor that inhibits the activity of native USP1/UAF1 with IC50 of 544 nM.
Biological Activity
sjb2-043 is a novel and potent inhibitor of usp1 with ic50 value of 0.544 μm [1].ubiquitin-specific protease 1 (usp1) is a deubiquitinating enzyme (dub) and is a member of the ubiquitin-specific processing (ubp) family of proteases. it deubiquitinates a protein in the dna repair pathway of the fanconi anemia (fa) [1].in the k562 cell line, sjb2-043 decreased usp1 levels in a dose-dependent way and caused degradation of the id1 protein, which resulted from proteasomal degradation. also, sjb2-043 decreased the levels of id2 and id3 proteins. importantly, knockdown of usp1 inhibited cell growth and increased apoptosis. in primary aml cells, sjb2-043 inactivated usp1 and promoted id 1 degradation. in primary human cord blood cd34+ cells, sjb2-043 in low micromolar levels inhibited cell growth. in hela cells, sjb2-043 increased the levels of ub-fancd2 and ub-pcna. and deubiquitination of fancd2 is an important step in the brca/fanconi anemia (fa) dna repair pathway [1].
References
[1]. helena mistry, grace hsieh, sara s, et al. buhrlage, et al. small molecule inhibitors of usp1 target id1 degradation in leukemic cells. mol cancer ther, 2013, 12(12): 2651-2662.
