Quisinostat (DB12985): A Comprehensive Review of Its Preclinical and Clinical Development as an HDAC Inhibitor in Oncology

1. Executive Summary

Quisinostat (DrugBank ID: DB12985; CAS Number: 875320-29-9), also known by its development code JNJ-26481585, is an orally bioavailable, second-generation hydroxamic acid-based histone deacetylase (HDAC) inhibitor. It exhibits potent, sub-nanomolar inhibitory activity against Class I HDACs, particularly HDAC1, and modest activity against certain Class II HDACs. Its mechanism of action involves the induction of histone hyperacetylation, leading to chromatin remodeling, altered gene expression, and ultimately, anti-tumor effects such as apoptosis, cell cycle arrest, and inhibition of tumor cell proliferation. Quisinostat also influences the acetylation status of non-histone proteins, contributing to its complex biological activity.

Developed initially by Janssen Pharmaceuticals and later co-developed in specific regions by NewVac LLC, Quisinostat has undergone extensive preclinical evaluation demonstrating broad in vitro cytotoxicity against various cancer cell lines and in vivo efficacy in several xenograft models, including notable activity as a brain-penetrant radiosensitizer in glioblastoma models.