Description
Tubastatin A (1310693-92-5) is a potent and highly selective inhibitor of HDAC6 (IC50?= 15 nM, >1000-fold selectivity against other HDAC isoforms, approx. 60-fold versus HDAC8).1?It displayed anti-inflammatory and anti-rheumatic effects in Freund’s competitive adjuvant induced animal model of inflammation.2?Tubastatin A inhibited TNF-α (IC50?= 272 nM) and IL-6 (IC50 = 712 nM) in LPS stimulated human THP-1 macrophages.2?Tubastatin A has also been shown to have therapeutic potential for treatment of Alzheimer’s disease via altered amyloid-β load and reduced tau hyperphosphorylation.3-5
Uses
Tubastatin A Hydrochloride is a neuroprotective HDAC6 inhibitor and is also known to induce hyperacetylation in primary cortical neuron cultures.
Biological Activity
Tubastatin A hydrochloride is a potent and selective inhibitor of HDAC6.
Biochem/physiol Actions
Tubastatin A increases the total numbers of mitochondria and restores the number of moving mitochondria in DRG neurons. It reverses the axonal loss in peripheral neurons in mouse model of Charcot-Marie-Tooth disease. Tubastatin A inhibits the deacetylation of α-tubulin in murine myoblasts.
References
1) Butler?et al. (2010),?Rational design and simple chemistry yield a superior, neuroprotective HDAC6 inhibitor, tubastatin A; J. Am. Chem. Soc.,?132?10842
2) Vishwakarma?et al. (2013),?Tubastatin, a selective histone deacetylase 6 inhibitor shows anti-inflammatory and anti-rheumatic effects; Int. Immunopharmacol.,?16?72
3) Noack and Richter-Landsberg (2014),?HDAC6 inhibition results in tau acetylation and modulates tau phosphorylation and degradation in oligodendrocytes; Glia,?62?535
4) Selenica?et al. (2014),?Histone deacetylase 6 inhibition improves memory and reduces total tau levels in a mouse model of tau deposition; Alzheimers Res.Ther.,?6?12
5) Zhang?et al. (2014)?Tubastatin A/ACY-1215 improves cognition in Alzheimer’s disease transgenic mice; J. Alzheimers Dis.,?41?1193
