QC-01-175   Click here for help

GtoPdb Ligand ID: 10544

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.
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 12
Hydrogen bond donors 4
Rotatable bonds 15
Topological polar surface area 171.82
Molecular weight 626.25
XLogP 0.98
No. Lipinski's rules broken 2
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES O=C(CCc1ccc2c(c1)[nH]c1c2cncc1)NCCOCCOCCNc1cccc2c1C(=O)N(C2=O)C1CCC(=O)NC1=O
Isomeric SMILES O=C(CCc1ccc2c(c1)[nH]c1c2cncc1)NCCOCCOCCNc1cccc2c1C(=O)N(C2=O)C1CCC(=O)NC1=O
InChI InChI=1S/C33H34N6O7/c40-28(8-5-20-4-6-21-23-19-34-11-10-24(23)37-26(21)18-20)36-13-15-46-17-16-45-14-12-35-25-3-1-2-22-30(25)33(44)39(32(22)43)27-7-9-29(41)38-31(27)42/h1-4,6,10-11,18-19,27,35,37H,5,7-9,12-17H2,(H,36,40)(H,38,41,42)
InChI Key NWTCZTAQSRLSCP-UHFFFAOYSA-N
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
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
microtubule associated protein tau Hs None Binding 5.9 pKd - 1
⤷ pKd 5.9 (Kd 1.2x10-6 M) [1]
Description: In vitro binding affinity for wild-type human tau determined using a biolayer interferometry (BLI) assay.