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P5091 (P005091) is a novel potent and selective inhibitor of ubiquitin-specific protease 7 (USP7) with an IC₅₀ ~4.2 μM. It does not inhibit other DUBs or other families of cysteine proteases tested (EC₅₀ > 100 mM). It induces apoptosis in MM cells resistant to conventional and bortezomib therapies. Biochemical and genetic studies showed that blockade of HDM2 and p21 abrogated P5091-induced cytotoxicity. In animal tumor model studies, P5091 was well tolerated, and it inhibited tumor growth, and prolongs survival. Combining P5091 with lenalidomide, HDAC inhibitor SAHA, or dexamethasone triggered synergistic anti-MM activity.

How to Use:

• In vitro: P5091 was used at 5-12.5 µM final concentration in various in vitro assays.
• In vivo: P5091 was administered through IV injection at 10 mg/kg twice weekly for 3 weeks.

Reference:

1. 1. Chauhan D, et al. A small molecule inhibitor of ubiquitin-specific protease-7 induces apoptosis in multiple myeloma cells and overcomes bortezomib resistance. (2012) Cancer Cell. 22(3):345-58.