Identification of Potential Drug Targets of Calix[4]arene by Reverse Docking

Calixarenes are displaying great potential for the development of new drug delivery systems, diagnostic imaging, biosensing devices and inhibitors of biological processes. In particular, calixarene derivatives are able to interact with many different enzymes and function as inhibitors. By screening of the potential drug target database (PDTD) with a reverse docking procedure, we identify and discuss a selection of 100 proteins that interact strongly with calix[4]arene. We also discover that leucine (23.5%), isoleucine (11.3%), phenylalanines (11.3%) and valine (9.5%) are the most frequent binding residues followed by hydrophobic cysteines and methionines and aromatic histidines, tyrosines and tryptophanes. Top binders are peroxisome proliferator‐activated receptors that already are targeted by commercial drugs, demonstrating the practical interest in calix[4]arene. Nuclear receptors, potassium channel, several carrier proteins, a variety of cancer‐related proteins and viral proteins are prominent in the list. It is concluded that calix[4]arene, which is characterized by facile access, well‐defined conformational characteristics, and ease of functionalization at both the lower and higher rims, could be a potential lead compound for the development of enzyme inhibitors and theranostic platforms.