Background

• Trop2, CD47, and CD3 are critical targets in immuno-oncology, validated by antibodies but lacking small molecule ligands and biding pockets.

Methodology

• PPI targeting workflow of Receptor.AI. ‍
• The stock chemical space of 4.'5 M compounds.
• Binding assessment as a first stage of the project.

Results

• Trop2
  • 15 preliminary hits obtained through BLI assays.
  • 7 hits confirmed through Differential Scanning Fluorimetry (DSF) assay.
  • Structure–Activity Relationship (SAR) study showed that 3 classes of inhibitors are assessed.
  • Preliminary hits obtained through BLI assays.
  • Hits TP2-05 and TP2-31 were confirmed by DSF assay.

• CD47
  
  • 7 preliminary hits obtained through BLI assays.
  • All preliminary hits confirmed through Differential Scanning Fluorimetry (DSF) assay.
  • Structure–Activity Relationship (SAR) study showed that 2 classes of inhibitors are assessed.
  • Homogeneous Time-Resolved Fluorescence (HTRF) screening
(PPI destabilization assessment) demonstrated 7/25 (2nd batch) 
hits (3 lead CD47/SIRPa PPI interface disruptors).

• PD-L1
  
  • Homogeneous Time-Resolved Fluorescence (HTRF) screening
(PPI destabilization assessment) demonstrated 12/23 
PD1-PDL1 PPI interface disruptors.

• CD47
  
  • 3 preliminary hits obtained through BLI assays.
  • Differential Scanning Fluorimetry (DSF) assay revealed:
  • • CD3-7 shows specificity to CD3 εδ,
    • CD3-15 shows specificity to CD3 εγ,
    • CD3-30 is bispecific.