Putting a lid on cancer cell proteasomes
Blocking the catalytic activity of proteasomes is a tried-and-true strategy in multiple myeloma, but use of marketed inhibitors is limited by drug resistance and lack of efficacy in solid tumors. Now, a team from The Johns Hopkins University has discovered a compound that suppresses tumor growth in vitro and in animal models of multiple myeloma and ovarian cancer by blocking the regulatory subunit of proteasomes.
The molecule, RA190, could represent a new class of proteasome inhibitors for use in solid tumors and drug-resistant MM.1
The team is now working on enhancing the compound's drug-like properties by optimizing its formulation and is testing the compound and other derivatives in clinical isolates from patients with MM.
Proteasome inhibition has emerged as a valuable strategy in cancer, in which rapid proliferation leads to the buildup of proteins synthesized during cell division. The proteasome controls the protein