Title:Multi-targeted HDAC Inhibitors as Anticancer Agents: Current
Status and Future Prospective
Volume: 30
Issue: 24
Author(s): Vijay K. Patel, Ekta Shirbhate, Priya Tiwari, Rakesh Kore, Ravichandran Veerasamy, Achal Mishra and Harish Rajak*
Affiliation:
- Department of Pharmacy, Guru Ghasidas University, Bilaspur, 495 009, (C.G.), India
Keywords:
Histone deacetylase, HDAC inhibitor, anticancer, dual/multi-targeting, designing strategies, computational methods, recent development.
Abstract: Multi-targeted agents can interact with multiple targets sequentially, resulting
in synergistic and more effective therapies for several complicated disorders, including
cancer, even with relatively modest activity. Histone deacetylase (HDAC) inhibitors are
low molecular weight small compounds that increase the acetylation of histone and nonhistone
proteins, altering gene expression and thereby impacting angiogenesis, metastasis,
and apoptosis, among other processes. The HDAC inhibitors affect multiple cellular
pathways thus producing adverse issues, causing therapeutic resistance, and they have
poor pharmacokinetic properties. The designing of HDAC-based dual/multi-target inhibitor
is an important strategy to overcome adverse effects, drug resistance and increase the
effectiveness in controlling cancer. The selection of target combinations to design multitarget
HDAC inhibitor is generally accomplished on the basis of systematic highthroughput
screening (HTS), network pharmacology analysis methods. The identification
of the pharmacophore against individual targets is performed using rational or computation
methods. The identified pharmacophore can combine with merged, fused, or linked
with the cleavable or non-cleavable linker to retain the interaction with the original target
while being compatible with the other target. The objective of this review is to elucidate
the potential targets' design strategies, biological activity, and the recent development of
dual/multi-targeting HDAC inhibitors as potential anticancer agents. This review elucidates
the designing strategies of the potential target along with biological activity and the
recent development of dual/multi-targeting HDAC inhibitors as potential anticancer
agents. The development of HDAC-based dual/multi-target inhibitors is important for
overcoming side effects, drug resistance, and effective cancer control.
