HQ-415 is a class of clinically relevant bioactive metal chelators related to clioquinol. The effective concentration eliciting a EC50 for HQ-415 is 15 μM. IC50 value: 15 μM (EC50) in vitro: In TDP-43-expressing cells, CQ fails to synergize with HQ-161 and actually antagonizes HQ-161 rescuing activity. In contrast, despite the fact that CQ was completely inactive against TDP-43, it strongly synergized with HQ-415, decreasing the EC50 from 16 to 5 μM. HQ-415 is active in the TDP-43 model, but CQ was not HQ-161 and HQ-415 are retested in dose for their ability to rescue TDP-43. Both HQ-161 and HQ-415 rescue TDP-43 toxicity. In cells expressing α-syn, HQ-161, despite being inactive on its own, synergized with HQ-415, reducing the EC50 from 21 to 14 μM. HQ-415 strongly synergizes with CQ at multiple concentrations in cells expressing α-syn.

• . Tardiff DF, et al. Different 8-hydroxyquinolines protect models of TDP-43 protein, α-synuclein, and polyglutamine proteotoxicity through distinct mechanisms. J Biol Chem. 2012 Feb 3;287(6):4107-4120.  [Content Brief]