Therapeutic potential of HDAC6 inhibitor Tubastatin A in health and diseases: current perspective and future directions

Sonu Rajput; Sumeet Kumar Singh; Poonam Yadav; Amit Khurana; Ralf Weiskirchen; Umashanker Navik

doi:10.1016/j.mmr.2026.100024

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Therapeutic potential of HDAC6 inhibitor Tubastatin A in health and diseases: current perspective and future directions

REVIEW | Updated：2026-05-11

- Therapeutic potential of HDAC6 inhibitor Tubastatin A in health and diseases: current perspective and future directions
- Military Medical Research (2026)
- Affiliations：
  
  Department of Pharmacology, Central University of Punjab, Bathinda 151401, Punjab, India
  Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), RWTH Aachen University Hospital, D-52074 Aachen, Germany
- Author bio：
  
  Ralf Weiskirchen, rweiskirchen@ukaachen.de
  *Umashanker Navik, usnavik@gmail.com;
- Funds：
- DOI：10.1016/j.mmr.2026.100024
  CLC：
- Received：08 July 2025，
  
  Accepted：23 March 2026，
  
  Published：2026-04
- Accepted：
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Rajput S, Singh SK, Yadav P, Khurana A, Weiskirchen R, Navik U. Therapeutic potential of HDAC6 inhibitor Tubastatin A in health and diseases: current perspective and future directions. Mil Med Res. 2026;13(1):100024.
DOI：

Rajput S, Singh SK, Yadav P, Khurana A, Weiskirchen R, Navik U. Therapeutic potential of HDAC6 inhibitor Tubastatin A in health and diseases: current perspective and future directions. Mil Med Res. 2026;13(1):100024. DOI： 10.1016/j.mmr.2026.100024.

摘要

Abstract

Histone deacetylase 6 (HDAC6) is a unique

predominantly cytoplasmic enzyme that regulates a broad spectrum of cellular and physiological processes

including cell proliferation

migration

intracellular transport

and differentiation. Its distinct structural configuration

comprising two catalytic deacetylase domains and a zinc finger ubiquitin-binding domain (ZnF-BUZ)

enables HDAC6 to deacetylate a variety of non-histone substrates

such as α-tubulin

heat shock protein 90 (Hsp90)

cortactin

and peroxiredoxin (Prdx). Furthermore

HDAC6 plays a key role in cellular stress responses and cell survival by facilitating the clearance of misfolded proteins

inducing autophagy

and modulating the unfolded protein response. Despite its cytoprotective roles

HDAC6 has emerged as a therapeutic target due to its involvement in multiple pathological pathways and age-related disorders. Tubastatin A (Tub A)

a novel and highly selective HDAC6 inhibitor

demonstrates strong therapeutic potential against neurodegenerative

cardiovascular

autoimmune

metabolic

cancer

and other diseases. Tub A enhances the acetylation of both histone and non-histone proteins

thereby modulating gene expression and diverse cellular processes. It shows pharmacological effects

including anti-inflammatory

neuroprotective

anti-diabetic

anti-obesity

anti-oxidant

and other activities. Moreover

preclinical evidence suggests that Tub A effectively regulates multiple pathological pathways by inhibiting HDAC6

which contributes to ameliorating age-related disorders. Therefore

Tub A represents a promising epigenetic modulator with broad therapeutic relevance. Hence

further comprehensive and large-scale investigations are warranted to elucidate its clinical potential and its roles in disease management

as no clinical data related to Tub A activity are available. This review highlights the therapeutic potential of the selective HDAC6 inhibitor Tub A across various pathological conditions

discusses current preclinical findings

and outlines key challenges and future directions for clinical translation.

关键词

Keywords

references

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