Chemical Identity

Property	Value
Chemical Formula	C19H25BN4O4
Molecular Weight	384.2 Da
CAS Number	179324-69-7
Peptide Class	Boronic Acid Dipeptide
Route	SC, IV

Structure

Bortezomib (Velcade) is a dipeptide boronic acid containing a pyrazinoic acid and a phenylalanine-leucine boronic acid moiety. The boronic acid group forms a reversible covalent bond with the catalytic threonine of the 20S proteasome beta5 subunit.

Mechanism of Action

Bortezomib reversibly inhibits the 20S proteasome’s chymotrypsin-like activity, preventing degradation of pro-apoptotic proteins, cell cycle regulators, and NF-kB inhibitors. Accumulation of misfolded proteins triggers the unfolded protein response and apoptosis, particularly in myeloma cells with high protein synthesis rates.

Clinical Applications

• Multiple myeloma: First-line and relapsed/refractory (Velcade)
• Mantle cell lymphoma: After one prior therapy
• AL amyloidosis: Off-label with dexamethasone
• Chronic graft-versus-host disease: Off-label

Pharmacokinetics

• Half-life: 9-15 hours
• Protein binding: 83%
• Metabolism: CYP3A4, CYP2C19, CYP1A2
• Elimination: Hepatic
• Route: SC (preferred) or IV (days 1, 4, 8, 11 of 21-day cycle)

Safety and Side Effects

Peripheral neuropathy (dose-limiting), thrombocytopenia, nausea, diarrhea, fatigue, herpes zoster reactivation, and tumor lysis syndrome. SC administration reduces neuropathy incidence.

References

• Richardson, P.G., et al. (2003). APEX trial: bortezomib for multiple myeloma. New England Journal of Medicine, 352, 2487-2498.
• San Miguel, J.F., et al. (2008). VISTA trial: bortezomib plus melphalan. New England Journal of Medicine, 359, 906-917.