Target ValidationMarch 2024
CD74 Trimer Biology: Why Quaternary Structure Matters for Drug Design
Accumulating evidence confirms that the CD74 ectodomain forms a stable homotrimer (PDB 1IIE, NMR). 68% of residues in the trimer domain are buried at the inter-monomer interface, making monomer-based docking biologically invalid for drug design.
JFInnova Perspective
This finding was a turning point for JFInnova. After discovering our original candidate (JFIN-0001) sterically clashed with the trimer, we pivoted in 48 hours using ESM-2 directed evolution and HDOCK docking against the experimental trimer structure, generating 48 new candidates.
References
1
Structure of the trimerization domain of the CD74 ectodomain
PDB / NMR · 2003
CD74 trimer structure quaternary drug design