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

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.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

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