Tubastatin A HCl | HDAC6 inhibitor

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

References/Citations:

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