VELCADE 3.5MG PD. IN VIAL FOR I.V. INJ

MECHANISM OF ACTION BORTEZOMIB IS A REVERSIBLE INHIBITOR OF THE CHYMOTRYPSIN-LIKE ACTIVITY OF THE 26S PROTEASOME IN MAMMALIAN CELLS. THE 26S PROTEASOME IS A LARGE PROTEIN COMPLEX THAT DEGRADES UBIQUITINATED PROTEINS. THE ACTIVE SITE OF THE PROTEASOME HAS CHYMOTRYPSIN-LIKE TRYPSIN-LIKE AND POSTGLUTAMYL PEPTIDE HYDROLYSIS ACTIVITY. THE 26S PROTEASOME DEGRADES VARIOUS PROTEINS CRITICAL TO CANCER CELL SURVIVAL SUCH AS CYCLINS TUMOR SUPPRESSORS BCL-2 AND CYCLIN-DEPENDENT KINASE INHIBITORS. INHIBITION OF THESE DEGRADATIONS SENSITIZES CELLS TO APOPTOSIS. BORTEZOMIB IS A POTENT INHIBITOR OF 26S PROTEASOME WHICH SENSITIZES ACTIVITY IN DIVIDING MULTIPLE MYELOMA AND LEUKEMIC CELLS THUS INDUCING APOPTOSIS. IN ADDITION BORTEZOMIB APPEARS TO INCREASE THE SENSITIVITY OF CANCER CELLS TO TRADITIONAL ANTICANCER AGENTS (E.G. GEMCITABINE CISPLATIN PACLITAXEL IRINOTECAN AND RADIATION).