Description
Dihydroeponemycin is a natural, irreversible inhibitor of proteasomal degradation of proteins that acts by binding the IFN-γ-inducible proteins LMP2 and LMP7, as well as the constitutive proteasome subunit X. It potently inhibits both the chymotrypsin-like and PGPH activity, with 10-fold less inhibition of trypsin-like activity. Dihydroeponemycin does not inhibit calpain or trypsin and has minor effects on cathepsin B and chymotrypsin at higher concentrations. It is cell-permeable and induces apoptosis in bovine aortic endothelial cells.
Uses
Dihydroeponemycin, an analogue of the antitumor and antiangiogenic natural product eponemycin, selectively targets the 20S proteasome. Dihydroeponemycin covalently modifies a subset of catalytic proteasomal subunits, binding preferentially to the IFN-gamma-inducible subunits LMP2 and LMP7. Dihydroeponemycin-mediated proteasome inhibition induces a spindle-like cellular morphological change and apoptosis[1].
References
[1] Meng L, et al. Eponemycin exerts its antitumor effect through the inhibition of proteasome function. Cancer Res. 1999;59(12):2798-2801. PMID:10383134
