Piptide Chemotypes for Perturbation of the Interaction of Urokinase with Its Receptor. Academic Article uri icon


  • Only a few small molecules that disrupt the uPA and uPA receptor (uPAR) interaction have been discovered despite decades of research in the area, and none have been approved in clinical trials. Research reported here features two new ways of considering the problem of discovering small molecules to disrupt uPAuPAR, specifically in terms of chemotype design and method of evaluation. Chemotypes used in this work are piptides (Arancillo . Angew. Chem., Int. Ed., 2021, 60, 6653-6659) with side chains corresponding to the uPA loop that binds uPAR. Further, hybrids of 1 and another uPAR ligand developed in these labs (2), i.e., 3 and 4, were also designed and tested. All the piptide chemotypes bound uPAR at concentrations of 50 M or less. Members of this series had Ki values <3 M and showed favorable responses in cellular assays; these data are comparable with the best small molecule uPAuPAR disruptors in the literature (from conventional screening).

published proceedings

  • J Med Chem

author list (cited authors)

  • Arancillo, M., Lin, C., & Burgess, K.

citation count

  • 0

complete list of authors

  • Arancillo, Maritess||Lin, Chen-Ming||Burgess, Kevin

publication date

  • October 2022