Proteasome Inhibitor X, PI-083

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.

Packaged under inert gas

Toxicity: Standard Handling (A)

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

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

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