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PYR-41 is a specific and cell permeable inhibitor of ubiquitin-activating enzyme E1 with an IC₅₀ of < 10 uM, with no or little activity against E2. It blocks ubiquitylation and prevents ubiquitin-mediated proteasomal degradation. It inhibits NF-κB activation, blocks degradation of p53, increases p21 levels and induces apoptosis in vitro. PYR-41 can also cause an increase in sumoylation of proteins.

How to Use:

• In vitro: PYR-41 was used at 10-50 µM final concentration in various in vitro assays.
• In vivo: n/a

Reference:

1. 1. Yang Y, et al. Inhibitors of ubiquitin-activating enzyme (E1), a new class of potential cancer therapeutics. (2007) Cancer Res. 67(19):9472-81.
2. 2. Kapuria V, et al. Protein cross-linking as a novel mechanism of action of a ubiquitin-activating enzyme inhibitor with anti-tumor activity. (2011) Biochem Pharmacol. 82(4):341-9.
3. 3. Ungermannova D, et al. Identification and mechanistic studies of a novel ubiquitin E1 inhibitor. (2012) J Biomol Screen. 17(4):421-34.