Bortezomib (Mechanism of Action)

In this article, we will discuss Bortezomib (Mechanism of Action). So, let’s get started.

Bortezomib for injection is an antineoplastic agent available for intravenous injection. Each single-dose vial contains 3.5 mg of bortezomib, 10.5 mg boric acid, 25 mg glycine as a sterile lyophilized powder.

The chemical name for bortezomib, the monomeric boronic acid, is [(1R)-3-methyl-1 – [[(2S)-I-oxo-3-phenyl-2-
[(pyrazinylcarbonyl) amino]propyl]amino]butyl] boronic acid. The molecular weight of bortezomib is 384.24 and its molecular formula is C19H25BN4O4.
The solubility of bortezomib, as the monomeric boronic acid, in water is 3.3 to 3.8 mg/mL in a pH range of 2 to 6.5

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 ubiquitin-proteasome pathway plays an essential role in regulating the intracellular concentration of specific proteins,
thereby maintaining homeostasis within cells. Inhibition of the 26S proteasome prevents this targeted proteolysis, which can affect multiple signaling cascades within the cell. This disruption of normal
homeostatic mechanisms can lead to cell death Experiments have demonstrated that bonezomib is cytotoxic to a variety of cancer cell types in vitro, Bortezomib causes a delay in tumor growth in vno in nonclinical tumor models, including multiple myeloma.

Pharmacodynamics

Following twice weekly administration of 1 mg/m² and 1.3 mg/m² bortezomib doses (n=12 per each dose level), the maximum inhibition of 20 proteasome activity (relative to baseline) in whole blood was observed 5 minutes after drug administration. Comparable maximum inhibition of 20 proteasome activity was observed between 1 and 1.3 mg/m² doses. Maximal inhibition ranged from 70% to 84% and from 73% to 83% for the
1 mg/m² and 1.3 mg/m² dose regimens, respectively.

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