PBA-1105 TFA is an autophagy-targeting chimera (AUTOTAC) that induces p62 self-oligomerization. This compound selectively binds to the exposed hydrophobic regions of misfolded proteins, promoting their degradation through the autophagy (autophagy) pathway. Additionally, PBA-1105 TFA enhances the autophagic flux of Ub-bound aggregates.

PBA-1105 TFA induces the autophagic degradation of stably expressed mutant tau at a concentration of DC 50 = 0.71 nM and D max, 24 hr = 100 nM, with a subsequent hook effect at higher concentrations [1]. At nanomolar concentrations (0.1-10 μM; 24 hours), PBA-1105 (TFA) promotes the autophagic breakdown of misfolded proteins and aggregates. PBA-1105 TFA significantly degrades mutant tau and misfolded proteins [1].

The administration of PBA-1105 (20-50 mg/kg; intraperitoneal injection; three times a week; for 4 weeks) effectively reduced tau aggregation and oligomer species in a transgenic mouse model of tauopathies [1].