| Identification | Back Directory | [Name]
N-[13-[3,4-Bis(phenylmethoxy)phenyl]-3,6,9-trioxa-12-azatridec-1-yl]benzenebutanamide | [CAS]
2410081-56-8 | [Synonyms]
N-[13-[3,4-Bis(phenylmethoxy)phenyl]-3,6,9-trioxa-12-azatridec-1-yl]benzenebutanamide | [Molecular Formula]
C39H48N2O6 | [MOL File]
2410081-56-8.mol | [Molecular Weight]
640.81 |
| Chemical Properties | Back Directory | [Boiling point ]
792.4±60.0 °C(Predicted) | [density ]
1.128±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted) | [form ]
Liquid
(Density: 1.129±0.06 g/cm3) | [pka]
15.60±0.46(Predicted) | [color ]
Colorless to light yellow |
| Hazard Information | Back Directory | [Uses]
PBA-1105 is an autophagy-targeting chimera (AUTOTAC) that induces p62 self-oligomerization. PBA-1105 selectively binds to exposed hydrophobic regions of misfolded proteins, facilitating their degradation via the autophagic pathway. PBA-1105 increases the autophagic flux of Ub-conjugated aggregates[1]. | [in vivo]
PBA-1105 (20-50 mg/kg; intraperitoneal injection; three times per week; for 4 weeks) successfully reduces tau aggregation and oligomeric species in a transgenic mouse model of tauopathies[1]. | Animal Model: | hTauP301L-BiFC transgenic mice[1] | | Dosage: | 20 or 50 mg/kg (PBS containing 30% polyethylene glycol (PEG)) | | Administration: | Intraperitoneal injection; three times per week; for 4 weeks | | Result: | Effectively cleared tau aggregates in a dose-dependent manner, significantly reducing insoluble tau species in the brain while leaving soluble tau species unaffected.
Resulted in increased levels of autophagic markers like LC3, confirming the activation of autophagic degradation pathways.
Immunohistochemical analysis showed a marked reduction in tau oligomers and phosphorylated tau in both cortical and hippocampal regions.
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| [References]
[1] Chang Hoon Ji, et al. The AUTOTAC chemical biology platform for targeted protein degradation via the autophagy-lysosome system. Nat Commun. 2022 Feb 16;13(1):904. DOI:10.1038/s41467-022-28520-4 |
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