C527

C527 is a is a pan DUB enzyme inhibitor, with a high potency for the USP1/UAF1 complex (IC50=0.88 μM).

Signaling Pathways >> Cell Cycle/DNA Damage >> Deubiquitinase

Research Areas >> Cancer

0.88 μM (USP1)[1]

Pretreatment of USP1/UAF1 with C527 resulted in inhibition of its enzyme activity with an IC50 of 0.88±0.03 μM. C527 inhibits the DUB activity of the USP12/USP46 complex and other DUB enzymes in vitro. However, the IC50 of C527 for these DUB enzymes was higher in comparison with USP1/UAF1 complex. C527 has considerably less inhibitory effect on UCH-L1 and UCH-L3, a different subclass of DUB enzymes. C527 treatments causes an increase in the levels of Ub-FANCD2 and Ub-FANCI. Pretreatment of cells with the C527 causes an enhancement in the cytoxicity of mitomycin C and camptothecin. C527 treatments lead to an increase in ubiquitinated forms of FANCD2 and FANCI, cause a decrease in homologous recombination activity, and sensitize cells to DNA damaging agents[1].

HeLa cells are treated with DMSO or C527 (0.5, 1, 5 μM) in appropriate medium for 24 to 72 hours. The viable cell counts are determined using Trypan Blue staining, CellTiter-Glo reagent or MTT assay[1].

[1]. Mistry H, et al. Small-molecule inhibitors of USP1 target ID1 degradation in leukemic cells. Mol Cancer Ther. 2013 Dec;12(12):2651-62.

BAY 11-7082 | P5091 | PR-619 | VLX1570 | Degrasyn(WP1130) | P 22077 | DUBs-IN-2 | ML364 | NSC 687852 | GNE-6776 | ML 323 | HBX 19818 | IU1 | LDN-57444