marizomib

Marizomib is a structurally unique, irreversible proteasome inhibitor derived from marine actinomycetes. It covalently binds to and inhibits all three proteolytic activities of the 20S catalytic core subunit of the proteasome by modifying its active site threonine residues, leading to an accumulation of polyubiquitinated proteins and disruption of cellular homeostasis[1][2][6]. This results in apoptosis in cancer cells through increased reactive oxygen species (ROS) production and caspase activation[6]. Marizomib has demonstrated efficacy as a single agent and in combination with other therapies across various hematologic malignancies (including multiple myeloma, mantle cell lymphoma, Waldenstrom’s macroglobulinemia, chronic and acute lymphocytic leukemia) as well as solid tumors such as glioblastoma, colorectal cancer, pancreatic cancer, cervical cancer, and others[2][3][8]. Notably, it can cross the blood-brain barrier—a property that distinguishes it from other proteasome inhibitors—making it particularly promising for central nervous system tumors like glioblastoma[6][7]. Marizomib was originally developed by Nereus Pharmaceuticals; development has continued under Celgene (now part of Bristol Myers Squibb), with additional involvement from organizations such as Canadian Cancer Trials Group and National Cancer Institute (USA)[7].

Other names

marizomib