Recent studies have suggested that certain over-expressed receptors may play an important role in the development and growth of pancreatic cancers. Cholecystokinin (CCKR) receptor, encodes a G-protein-coupled receptor that binds cholecystokinin (CCK) family of peptide hormones while epidermal growth factor receptor (EGFR) is a tyrosine kinase family of growth receptors. Both these receptors have been found to be over-expressed in pancreatic cancers and therefore are considered drug targets. In this work we have designed receptor targeted peptide conjugated heterocyclic compounds comprised of functionalized pyrmidines and cholesterol mimics that can specifically be utilized for targeting the CCKAR and CCKBR receptors and EGFR receptors. The purpose of this study was to characterize the binding interactions of with six peptide based novel drug candidates and to correlate receptor binding studies using docking and 3D QSAR modeling studies as well as pharmacokinetic analysis using ADME. Our results indicated that bioavailablity of the molecules were in the range of 0.17 to 0.20, and the ilogP was found to be in the range of 2.00 to 2.19 indicating that the molecules were membrane permeable. Furthermore, overall the drugs showed a higher binding affinity when the heterocyclic compounds were attached to the targeted peptides compared to the peptides alone.

Design of new peptide-conjugates for targeting cholecystokinin and epidermal growth factor receptors for targeting cancer

ACS Spring Meeting 2021

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