What it is
Bortezomib is two amino-acid units with a boron atom where a carboxyl group should be. The Velcade label calls it "a modified dipeptidyl boronic acid." Read from its chemical name, the molecule is a pyrazine ring cap, then phenylalanine, then a leucine whose carboxyl end has been replaced by boronic acid (our reading of the label name). Formula C19H25BN4O4, molecular weight 384.24.
That makes it an edge case among peptide drugs: it is built on the same peptide bond as any chain, but the boron end, not the amino acids, does the work. In the vial it is a mannitol ester, and in solution it exists in equilibrium with the free boronic acid (label).
How it works
Cells dispose of unwanted proteins by tagging them with ubiquitin and feeding them to the 26S proteasome, a barrel-shaped protein complex. Bortezomib is "a reversible inhibitor of the chymotrypsin-like activity" of that complex (label): the boronic acid binds the proteasome's active site. Blocking it "can affect multiple signaling cascades within the cell" and "can lead to cell death." Myeloma cells, which manufacture antibodies in bulk, are especially exposed. Its successor carfilzomib works on the same machine with a different, irreversible chemistry.
What the label's trials show
| Use (label) | Trial | Result |
|---|---|---|
| Untreated myeloma | NCT00111319, 682 patients, bortezomib + melphalan + prednisone vs melphalan + prednisone, open-label | Time to progression 20.7 vs 15.0 months (HR 0.54); overall survival at 60.1 months 56.4 vs 43.1 months (HR 0.695) |
| Relapsed myeloma | NCT00048230, 669 patients, bortezomib vs high-dose dexamethasone, open-label | Time to progression 6.2 vs 3.5 months |
| Untreated mantle cell lymphoma | NCT00722137, 487 patients, VcR-CAP vs R-CHOP | Progression-free survival 25 vs 14 months (HR 0.63); complete response 44% vs 34% |
All three trials were open-label: patients and doctors knew which treatment was given. In the first trial, enrolment was halted after a pre-specified interim analysis and patients on melphalan and prednisone were offered bortezomib; the label reports the later survival benefit as holding despite that crossover.
Nerve damage and the switch to under the skin
The label's first warning is peripheral neuropathy, mainly sensory — numbness, pain or burning in the hands and feet — sometimes severe. A trial of 222 relapsed patients compared routes: grade 2 or worse neuropathy in 24% under the skin vs 39% into a vein; grade 3 or worse in 6% vs 15%. The label also warns of low blood pressure, heart failure, lung toxicity, a brain-swelling syndrome (PRES), gastrointestinal toxicity and low platelets. Doses are set by body surface area on the label and decided by the treating team.
Where it stands
- Approved in the US since 2003-05-13 (Velcade, NDA 021602), for adults with multiple myeloma and mantle cell lymphoma.
- Generics: 19 bortezomib applications in Drugs@FDA; most generics were approved from 2022 onward (openFDA, 2026-10-14).
- Research record: PubMed indexes 12,882 records, 392 tagged as randomised trials (2026-10-14).
Related reading
The next-generation proteasome blocker is carfilzomib, a four-unit peptide. For other approved peptide drugs used in cancer care, see degarelix and the long-acting GnRH agonist leuprolide; for how a chain is joined, the peptide bond.