MPT0G211

SKU: orb1689411

Description

MPT0G211 is a potent, orally bioavailable, and brain-penetrant HDAC6 inhibitor with exceptional selectivity (IC50=0.291 nM). It demonstrates neuroprotective and anti-metastatic properties in cellular models and has been shown to ameliorate tau pathology and cognitive deficits in Alzheimer's disease animal studies.

Research Area

Epigenetics & Chromatin, Molecular Biology

Key Properties

• CAS Number: 2151853-97-1
• MW: 293.32
• Purity: 98.00% (May vary between batches)
• Formula: C₁₇H₁₅N₃O₂
• SMILES: ONC(=O)c1ccc(CNc2cccc3cccnc23)cc1
• Target: HDAC
• Solubility: DMSO:90 mg/mL (306.83 mM);10% DMSO+90% Saline:3.3 mg/mL (11.25 mM)

Bioactivity

• Target IC50:
  HDAC6:0.291 μM
• In Vivo:
  MPT0G211 (50 mg/kg; oral administration; daily for 3 months) significantly ameliorates spatial memory impairment. MPT0G211 (25 mg/kg; intraperitoneal injection; once daily; day 73 post-tumor injection) reduces the numbers of nodules and lung weights. 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.
  Read more...
• In Vitro:
  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. MPT0G211 inhibits HDAC6/Hsp90 binding, leading to subsequent proteasomal degradation of polyubiquitinated proteins. MPT0G211 significantly decreases the phosphorylation of tau through GSK3β inactivation. 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). MPT0G211 inhibits the growth of MDA-MB-231 and MCF-7 cells (GI50=16.19 and 5.6 μM, respectively).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.
  Read more...

Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

HDAC6

Compound Identifiers

PubChem CID

132157820