Our Partners


Circle has collaborated with Pfizer to develop orally bioavailable macrocyclic peptides against the chemokine receptor CXCR7, an attractive drug target for a variety of disease indications. Starting from a known cyclic peptide that was not significantly cell permeable and had only modest affinity for the CXCR7 target (Ki ~5 uM), we deployed computational prediction, peptoid substitutions to access chemical diversity beyond natural amino acids, and experimental assays to track polarity and improve physicochemical properties. We identified multiple new permeable scaffolds with activity against the target and also modified side chain residues on the initial scaffold. These strategies led to the discovery of several new cell permeable macrocyclic peptide-peptoid hybrids with superior CXCR7 binding affinities (Ki < 100 nM), including a potent bioactive compound (Ki =9nM) which achieved 18% oral bioavailability in rats. This work has now been published in the Journal of Medicinal Chemistry.

Circle is open to additional partnering collaborations with pharmaceutical and biotechnology companies who share our excitement in the potential of macrocyclic peptides. Please contact us at partnering@circlepharma.com.