General description
BIO-2007817 is a small-molecule compound identified as a positive allosteric modulator (PAM) of the Parkin E3 ubiquitin ligase. This compound belongs to the tetrahydropyrazolo-pyrazine class and has been shown to significantly enhance the activity of wildtype Parkin.
Application
BIO-2007817 has been used in ubiquitination assays and isothermal titration calorimetry to study the mechanism of activation of Parkin.
Biochem/physiol Actions
BIO-2007817 enhances Parkin activation by facilitating the interaction between the RING0 domain of Parkin and phospho-ubiquitin (pUb). It binds selectively to Parkin with an EC50 of 150 nM, acting as a molecular glue between Parkin and pUb, promoting autoubiquitination and the ubiquitination of mitochondrial proteins like mitofusin-2 (Mfn2). However, BIO-2007817 does not promote Parkin translocation to depolarized mitochondria in HeLa cells nor enhance mitophagy in MitoQC SH-SY5Y cell lines. Despite this, it shows no significant off-target effects and partially rescues the activity of disease-associated Parkin mutants.
| Quality Segment | 100 |
| assay | ≥98% (HPLC) |
| form | powder |
| color | white to beige |
| solubility | DMSO: 2 mg/mL, clear |
| storage temp. | -10 to -25°C |
