Fragment-Based Approach towards the Design of Potent and Versatile Anti-Cancer Agents

Abstract

Despite years of clinical research and trials of encouraging new therapies, cancer remains a leading cause of morbidity and mortality. The fragment-based drug discovery has evolved formerly as an efficient approach for identification, optimization, and generation of lead. After identifying the fragments having binding affinity with the target using computational method for fragment screening, they are optimized into more active compounds. This review elaborates the application of methodology of fragment-based drug design in designing potent and versatile anti-cancer drug candidates. It comprises of details such as construction of fragment library and screening, principles of library design, fragment hit identification, fragment to lead optimization, deconstruction and reconstruction approach, unified fragment based QSAR technique, phytochemical and pharmacophoric fragment based drug development and FBDD based targeting of epigenetic regulators in cancer. The agents discussed include STAT-3 inhibitor, vemurafenib, pazopanib, TAS-116 HSP-90 α/β inhibitor, pexidartinib, venetoclax and erdafitinib, FBDD based designed Anticancer Agents.