MPT0G211 mesylate is a powerful and selective HDAC6 inhibitor (IC50 = 0.291 nM), with high oral bioavailability. It exhibits remarkable selectivity for HDAC6 over other HDAC isoforms (>1000-fold selectivity). Additionally, MPT0G211 mesylate can effectively cross the blood-brain barrier. In preclinical studies using an Alzheimer's disease model, MPT0G211 mesylate has shown promising results in reducing tau phosphorylation and cognitive deficits. Furthermore, this compound exhibits anti-metastatic and neuroprotective effects, making it a potential candidate for anticancer interventions. [1] [2] [3].

MPT0G211 mesylate (0.1 μM; Cells were transfected with pCAX APP 695 and pRK5-EGFP-Tau P301L for 24 h) significantly inhibited the phosphorylation of tau Ser396 [1]. MPT0G211 mesylate inhibits HDAC6/Hsp90 binding and causes subsequent proteasomal degradation of polyubiquitinated proteins [1]. MPT0G211 mesylate significantly decreases the phosphorylation of tau by GSK3β inactivation [1]. MPT0G211 mesylate (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 mesylate inhibits MDA-MB-231 and MCF-7 cells growth (GI 50 =16.19 and 5.6 μM, respectively) [2]. In AML cells, MPT0G211 mesylate potentiates the cytotoxic effects of DOXO by impairing DNA repair machinery and activating Bcl-2-associated X protein (BCL-XL)-dependent cell apoptosis [3].

MPT0G211 mesylate (50 mg/kg; p.o.; daily for 3 months) significantly ameliorates the spatial memory impairment [1]. MPT0G211 mesylate (25 mg/kg; i.p.; qd; day 73 post-tumor injection) reduces numbers of nodules and lung weights [2]. MPT0G211 mesylate 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]. Animal Model: Triple transgenic (3×Tg-AD) mice (harboring APP Swe and tau P301L mutant transgenes [1] Dosage: 50 mg/kg Administration: P.o.; daily for 3 months Result: Significantly ameliorated the spatial memory impairment. Animal Model: Female SCID mice (bearing MDA-MB-231 cells) [2] Dosage: 25 mg/kg Administration: I.p.; qd; day 73 post-tumor injection Result: Significantly reduced numbers of nodules and lung weights.