MPT0G211

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

MPT0G211 是一种新型有效的选择性 HDAC6 抑制剂，IC50 为 0.291 nM。

MPT0G211 is a novel potent, selective HDAC6 inhibitor with IC50 of 0.291 nM, displays >1,000-fold selectivity over other HDAC isoforms; significantly inhibits tau phosphorylation on Ser396, Ser404, and phosphorylated tau (p-tau) aggregation, significantly attenuates apoptosis induced by p-tau, inhibits HDAC6/Hsp90 binding and causes subsequent proteasomal degradation of polyubiquitinated proteins; ameliorates learning and memory impairment in animal models of Alzheimer's disease, reduces the amount of phosphorylated tau in the hippocampal CA1 region; also demonstrates antiproliferative activity against human multiple myeloma RPMI 8226, U266, and NCI-H929 cells with no effect on normal bone marrow cells.

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.MPT0G211 inhibits HDAC6/Hsp90 binding and causes subsequent proteasomal degradation of polyubiquitinated proteins.MPT0G211 significantly decreases the phosphorylation of tau by GSK3β inactivation.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).MPT0G211 inhibits MDA-MB-231 and MCF-7 cells growth (GI50=16.19 and 5.6 μM, respectively).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.

MPT0G211 (50?mg/kg; p.o.; daily for 3 months) significantly ameliorates the spatial memory impairment.MPT0G211 (25?mg/kg; i.p. ; qd; day 73 post-tumor injection) reduces numbers of nodules and lung weights.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. Animal Model:Triple transgenic (3×Tg-AD) mice (harboring APPSwe and tauP301L mutant transgenes 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)Dosage:25?mg/kg Administration:I.p.; qd; day 73 post-tumor injection Result:Significantly reduced numbers of nodules and lung weights.

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Cell Cycle/DNA Damage

HDAC

HDAC

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2151853-97-1

293.326

C17H15N3O2

>98% (HPLC)

In Vitro:?DMSO : 100 mg/mL (340.92 mM)

C1=CC2=C(C(=C1)NCC3=CC=C(C=C3)C(=O)NO)N=CC=C2

N-hydroxy-4-((quinolin-8-ylamino)methyl)benzamide

(-20℃)

With Ice Pack

≥ 2 years