Development of STimulator of Interferon Genes Agonists in Silico

Abstract

STimulator of Interferon Genes (STING) is now considered as a promising target for tumour immunotherapy. In normal cells, STING is able to activate the generation of Type I interferon (IFN) and in turn can induce the activity of T cells, but in cancer cells, the expression of STING is inhibited due to the hypomethylation of its promoter. Cyclic dinucleotides were taken as the agonists to trigger the cGAS/STING pathway in cancer cells. However, this type of agonist is hard to be administrated to patients with tumour, and thus the discovery of STING agonists focuses on the development of small molecular drugs. In developing small molecular drugs for target proteins, computer-aided drug discovery (CADD) is an important tool. The utilize of this tool can reduce waste of time and budget which are consumed in the development of ligands with traditional methods. In this research, Schrödinger, a type of CADD software, was utilized for virtual screening agonists for activating STING effectively. There were four ligands obtained after virtual screening the small molecule database, and their interaction with target protein was analysed and compared.