- Guide to PHARMACOLOGY
Synonyms: peptide boronate | PS-341 | Velcade®
bortezomib is an approved drug (FDA (2003), EMA (2004))
Compound class: Synthetic organic
Comment: Bortezomib is a dipeptide (Phe-Leu), with a pyrazinoic acid protecting the N-terminus and a boronic acid replacing the C-terminal carboxylic acid. The boron atom is believed to interact with and inactivate the catalytic site on β subunits which form the active core of the proteasome, preferentially binding β5 active site . Bortezomib is the first-in-class proteasome inhibitor to be approved for clinical use.
Proteasome activity is reviewed in .
The Malaria tab on this ligand page provides additional curator comments of relevance to the Guide to MALARIA PHARMACOLOGY.
Ligand Activity Visualisation Charts
These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.✖
|No information available.|
|Summary of Clinical Use|
|May be used to treat multiple myeloma in patients unsuccessfully treated with at least two previous therapies. Bortezomib is delivered by injection. The marketed drug Velcade, contains bortezomib as the mannitol boronic ester.|
|Mechanism Of Action and Pharmacodynamic Effects|
|Bortezomib is a reversible inhibitor of the chymotrypsin-like activity of the 26S proteasome. Inhibitors of proteasome activity are antiproliferative and pro-apoptotic in nature. Proteasome inhibition leads to an increase in intracellular pro-apoptotic proteins, which promote cell-cycle arrest and cell-death .|
|Bortezomib is primarily oxidatively metabolized via cytochrome P450 enzymes, 3A4, 2D6, 2C19, 2C9, and 1A2. Deboronated metabolites are inactive as 26S proteasome inhibitors.|
|The pathways of elimination of bortezomib have not been characterized in humans.|
For extended ADME data see the following:
Electronic Medicines Compendium (eMC)
European Medicines Agency (EMA)