MPT0G211 is a highly selective and orally active HDAC6 inhibitor (IC50=0.291 nM) that has neuroprotective effects and has shown anti-metastatic activity in human breast cancer cells. MPT0G211 has 1,000 times more affinity for HDAC6 than other HDAC subtypes. MPT0G211 can cross the blood-brain barrier and could be used to improve tau phosphorylation and cognitive deficits in Alzheimer's disease models.

HDAC6:0.291 μM

MPT0G211 (0.1 μM; cells transfected with pCAX APP 695 and pRK5-EGFP-Tau P301L for 24 h) significantly inhibits the phosphorylation of tau Ser396[3].
MPT0G211 inhibits HDAC6/Hsp90 binding, leading to subsequent proteasomal degradation of polyubiquitinated proteins[3].
MPT0G211 significantly decreases the phosphorylation of tau through GSK3β inactivation[3].
MPT0G211 (0.1 μM; 24 hours) significantly attenuates the phosphorylation of tau at Ser396 and Ser404 in both cell lines (SH-SY5Y and Neuro-2a cells transfected for 24 h with pCAX APP 695 and pRK5-EGFP-Tau P301L)[3].
MPT0G211 inhibits the growth of MDA-MB-231 and MCF-7 cells (GI50=16.19 and 5.6 μM, respectively)[2].In AML cells, MPT0G211 potentiates the cytotoxic effects of DOXO by impairing DNA repair machinery and activating Bcl-2-associated X protein (BCL-XL)-dependent cell apoptosis[1].

MPT0G211 (50 mg/kg; oral administration; daily for 3 months) significantly ameliorates spatial memory impairment[3].
MPT0G211 (25 mg/kg; intraperitoneal injection; once daily; day 73 post-tumor injection) reduces the numbers of nodules and lung weights[2].
MPT0G211 treatment not only diminishes tau phosphorylation by inhibiting GSK3β activity but also enhances the acetylation of Hsp90. This leads to the downregulation of HDAC6/Hsp90 binding and facilitates proteasomal degradation of polyubiquitinated phosphorylated tau[3].