Bortezomib, N pyrazinecarbony,l L phenylalanine, L leucine boronic acid previously known as PS 341, a modified dipeptidyl boronic acid derived from leucine and phenylalanine that reversibly hinders the threonine buildup of the 26S proteasome, a catalytic complex that assumes a vital part in the cell by regulating degradation of proteins in a synchronized fashion. Proteins that are never again required comprised of those associated with cell cycle control apoptosis and cell signaling are labeled with ubiquitin, which guides them to the proteasome, which therefore debases them. The synchrony of balance between stimulatory and inhibitory protein associated with the cell cycle is essential for optimum physiology of the cell, and small frailty may lead to the altered fate of the cell. In this context restraint of the proteasome, the key degenerative protein of the cell cycle brings about the significant alteration of the stringent regulatory procedure that maturates the cell cycle and ultimately leading to the cell demise 218 219. Recent mechanistic exploration of Bortezomib also evidenced dysregulation of intracellular calcium metabolism and subsequent actuation of caspase and apoptosis 220 Landowski et al 2005. Collectively the prime biological impact of Bortezomib includes repression of NF κ B and CDK development inhibition of angiogenesis cell adhesion and canonization of p53 p21 p27 PTEN ROS, and ultimately apoptosis 221 222. Preclinical proof demonstrated that Bortezomib initiates growth capture by means of arresting G2 M, stage of cell cycle and actuates apoptosis in human glioblastoma cell lines 223. However, phase I clinical trials on patients with recurrent glioblastoma demonstrated a partial response in a small percentage of the patient population getting Bortezomib treatment 224.
