Compound class:
Synthetic organic
Comment: QC-01-175 is a functional degrader of pathogenic tau protein [1]. It is a bifunctional molecule that simultaneously engages tau and cereblon (CRBN; a component of the E3 ubiquitin ligase complex) to trigger tau ubiquitination and proteasomal degradation. Such molecules can be described as PROTACs (proteolysis targeting chimeras). Cereblon engagement is mediated by the probe's pomalidomide module, and tau recruitment is achieved by a variant of the tau PET tracer T807 (flortaucipir (18F)). QC-01-175 retains the tau ligand-binding capacity of the parent T807, but with reduced off-target MAO inhibition liability.
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Bioactivity Comments |
QC-01-175 degrades tau with a DC50 of ~100 nM (after 24h treatment) in frontotemporal dementia patient-derived neuronal cells harbouring the MAPT A152T mutation [1]. DC50 is the concentration of test compound that degrades target protein by 50%. ZFP91, ZN653, ZN827 proteins are also degraded by QC-01-175, which is unsurprising as these are validated targets of immune-modulatory drug pomalidomide. |
Selectivity at ligand targets | ||||||||||||||||||||||||||||||||||
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