MPT0G211

MPT0G211 is a potent, orally active and selective HDAC6 inhibitor (IC₅₀=0.291?nM). MPT0G211 displays >1000-fold selective for HDAC6 over other HDAC isoforms. MPT0G211 can penetrate the blood-brain barrier. MPT0G211 ameliorates tau phosphorylation and cognitive deficits in an Alzheimer’s disease model. MPT0G211 has anti-metastatic and neuroprotective effects. Anticancer activities^[1][2][3]. In Vitro: MPT0G211 (0.1?μM; cells were transfected with pCAX APP 695 and pRK5-EGFP-Tau P301L for 24?h) significantly inhibits the phosphorylation of tau Ser396^[1].
MPT0G211 inhibits HDAC6/Hsp90 binding and causes subsequent proteasomal degradation of polyubiquitinated proteins^[1].
MPT0G211 significantly decreases the phosphorylation of tau by GSK3β inactivation^[1].
MPT0G211 (0.1?μM; 24 hours) significantly attenuates the phosphorylation of tau Ser396 and Ser404 in both cell lines (SH-SY5Y and Neuro-2a cells were transfected for 24?h with pCAX APP 695 and pRK5-EGFP-Tau P301L)^[1].
MPT0G211 inhibits MDA-MB-231 and MCF-7 cells growth (GI₅₀=16.19 and 5.6 μM, respectively)^[2].
In AML cells, MPT0G211 potentiated the cytotoxic effects of DOXO by impairing DNA repair machinery and activating Bcl-2-associated X protein (BCL-XL)-dependent cell apoptosis^[3]. In Vivo: MPT0G211 (50?mg/kg; p.o.; daily for 3 months) significantly ameliorates the spatial memory impairment^[1].
MPT0G211 (25?mg/kg; i.p. ; qd; day 73 post-tumor injection) reduces numbers of nodules and lung weights^[2].
MPT0G211 treatment not only diminishes tau phosphorylation by inhibition GSK3β activity but also enhances the acetylation of Hsp90, which causes the downregulation of HDAC6/Hsp90 binding and facilitates proteasomal degradation of polyubiquitinated p-tau^[1].