Tracing the Analytical Footprint of Belinostat: Exploring Pharmacology and Synthetic Framework.

Belinostat (PXD101), a hydroxamate-class histone deacetylase inhibitor (HDACi), was approved by the US FDA for patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). This review covers belinostat's pharmacological characteristics (including its mode of action), pharmacokinetics, toxicity, drug interactions, and analytical methods. Belinostat inhibits HDACs from Classes I and II, which then raises the acetylation of both histone and nonhistone proteins, resulting in growth cycle arrest and ultimately leading to the death of the malignant cells. The pharmacokinetics of belinostat include a brief elimination half-life and substantial first-pass metabolism in the liver, mostly via UGT1A1. Belinostat's efficacy has been proven in numerous clinical trials, which also revealed a certain level of cytotoxicity specific to tumor cells. Belinostat and its potential metabolites have often been qualitatively and quantitatively estimated and tracked using several analytical methods including UPLC-MS/MS, HPLC-UV, FTIR, TLC, NMR, and ESI-MS. In terms of therapeutic use of belinostat, this review demonstrates how important it is to understand the metabolism and degradation pathways of belinostat, as well as possible drug-drug interactions.