Epigenetic drug discovery field has evidenced significant advancement in the recent times. A plethora of small molecule inhibitors have progressed to clinical stage investigations and are being explored exhaustively to ascertain conclusive benefits in diverse malignancies. Literature precedents indicates that substantial amount of efforts were directed towards the use of epigenetic tools in monotherapy as well as in combination regimens at the clinical level, however, the preclinical/preliminary explorations were inclined towards the identification of prudent approaches that can leverage the anticancer potential of small molecule epigenetic inhibitors as single agents only. This review article presents an update of FDA approved epigenetic drugs along with the epigenetic inhibitors undergoing clinical stage investigations in different cancer types. A detailed discussion of the pragmatic strategies that are expected to steer the progress of the epigenetic therapy through the implementation of emerging approaches such as PROTACS and CRISPR/Cas9 along with logical ways for scaffold fabrication to selectively approach the enzyme isoforms in pursuit of garnering amplified antitumor effects has been covered. In addition, the compilation also presents the rational strategies for the construction of multi-targeting scaffold assemblages employing previously identified pharmacophores as potential alternatives to the combination therapy.

Glioblastoma (GBM) is a highly malignant brain tumor characterized by a heterogeneous population of genetically unstable and highly infiltrative cells that are resistant to chemotherapy. Although substantial efforts have been invested in the field of anti-GBM drug discovery in the past decade, success has primarily been confined to the preclinical level, and clinical studies have often been hampered due to efficacy-, selectivity-, or physicochemical property-related issues. Thus, expansion of the list of molecular targets coupled with a pragmatic design of new small-molecule inhibitors with central nervous system (CNS)-penetrating ability is required to steer the wheels of anti-GBM drug discovery endeavors. This Perspective presents various aspects of drug discovery (challenges in GBM drug discovery and delivery, therapeutic targets, and agents under clinical investigation). The comprehensively covered sections include the recent medicinal chemistry campaigns embarked upon to validate the potential of numerous enzymes/proteins/receptors as therapeutic targets in GBM.

Microtubules play an important role in several cellular processes, particularly in the formation of the mitotic spindle during the process of mitosis. These highly dynamic mitotic-spindle microtubules have become a successful target of cancer therapy. Microtubule-targeting agents, such as vinca alkaloids and taxanes, were used in clinic over 50 years. In past decades, development of new antimicrotubule agents that possess different structure and binding sites of tubulin has shown potent activity against the proliferation of various cancer cells, as well as in multidrug-resistant cancers. Interestingly, many of these agents represent an attractive ability that targeting the tumor blood vessels results in tumor vascular disruption. Therefore, exploring new agents and strategies may provide more effective therapeutic options in the related treatment of cancer. In past few years, there are many chemical compounds that successfully interferes the microtubules and display antitumor effect. In these, published compounds supply the fresh minds in modification of present drugs and new insights into the development of tubulin inhibitors. This article arranges the microtubule-targeting agents that have published in patent in recent years. It may help in the investigation of new tubulin binding site and development of novel drug candidate in the future.