MTK458

SKU: orb1744912

Description

MTK458 (EP-0035985) is an orally bioavailable, brain-penetrant small molecule activator of PINK1. It promotes the clearance of pathological alpha-synuclein in preclinical models, such as the PFF inoculation model, by stabilizing the PINK1/TOM complex. This compound is a valuable research tool for investigating Parkinson's disease mechanisms and potential therapeutic strategies.

Research Area

Cell Biology, Metabolism Research, Signal Transduction

Key Properties

• CAS Number: 2499962-58-0
• MW: 332.32
• Purity: 99.94% (May vary between batches)
• Formula: C₁₇H₁₅F₃N₄
• SMILES: N(C1=C2C(NC(C(F)(F)F)=C2)=NC=N1)[C@H]3C=4C(CCC3)=CC=CC4
• Target: PTEN,Mitophagy,Mitochondrial Metabolism
• Solubility: 10% DMSO+90% Corn Oil:3.3 mg/mL (9.93 mM);DMSO:80 mg/mL (240.73 mM)

Bioactivity

• In Vivo:
  In the striatum of mice injected with α-synuclein preformed fibrils (PFFs), Mitophagy activator 1 (50 mg/kg; oral gavage (p.o.), daily, for 6 months) rescued activity deficits in freely moving PFF mice and reduced the levels of inflammatory markers (TREM2, IL-6, and CXCL1).
  Read more...
• In Vitro:
  Mitophagy activator 1 (0.1-25 µM), as a brain-penetrant small molecule, binds to PINK1 and stabilizes the active heterocomplex, thereby enhancing mitochondrial autophagy. It clears pS129 α-synuclein aggregates in a dose-dependent manner at DIV9 and DIV12.
  Read more...

Storage & Handling

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

Alternative Names

Mitophagy activator 1, EP-0035985, PTEN-induced kinase 1 (PINK1)

Compound Identifiers

PubChem CID

155187445