Proteasome Inhibitor X, PI-083

Toxicity: Standard Handling (A)

A cell-permeable, reversible 20S proteasome inhibitor with IC₅₀ values of 1 µM, 4.5 µM and 4.5 µM for CT-L, T-L and PGPH-L respectively. Exhibits CT-L (chymotrypsin-like) and cell proliferation inhibition selectively in ovarian, pancreatic, and breast cancer cells (T80-Hras, C7-Kras, and MCF-7, respectively) over their non-transformed counterparts (T80, C7, and MCF-10A), and induction of apoptosis with IC₅₀ values of 3.7 µM in an MTT assay on bone marrow cells isolated from multiple myeloma patients in vitro. Shown to have anti-tumor activities in a nude mouse xenograft model implanted with MCF-7 and A549 cells in vivo when dosed at 1 mpk, leading to significant tumor growth inhibition of 84%. PI-083 results in 43, 12 and 34% inhibition of tumor CT-L, T-L and PGPH activities respectively, compared to those of tumors from vehicle-treated controls, while it does not inhibit liver proteasome activities.

Lawrence, R., et al. 2010. Bioorg. Med. Chem.18, 5576.
Kazi, A., et al. 2009. Cell Cycle8, 1940.

Packaged under inert gas

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany