Design of PD-L1 inhibitors for lung cancer.

Trishang Udhwani,Sanjeev Kumar Singh,Khushboo Sharma,Natasha Khandekar,Jajoriya Sweta,Anuraj Nayarisseri,Sourav Mukherjee

doi:10.6026/97320630015139

Abstract

The progression of lung cancer is associated with inactivation of programmed cell death protein 1, abbreviated as PD- 1 which regulates the suppression of the body's immune system by suppressing T- cell inflammatory activity and is responsible for preventing cancer cell growth. It is of interest to identify inhibitors for PD-L1 dimeric structure through molecular docking and virtual screening. The virtual screened compound XGIQBUNWFCCMAS-UHFFFAOYSA-N (PubChem CID: 127263272) displays a high affinity with the target protein. ADMET analysis and cytotoxicity studies further add weight to this compound as a potential inhibitor of PD-L1. The established compound BMS-202 still shows the high re-rank score, but the virtual screened drug possesses a better ADMET profile with a higher intestinal absorption value and lower toxicity.

Highlights

There are 8.8 million recorded deaths of malignant cancer every year according to WHO data and this number keep on increasing which is a clear indication of the threat this disease poses
Owing to the fact that the development of these small molecule inhibitors is relatively lacking, the present study aims to identify a potential small molecule inhibitor, which binds with PD-L1 with high affinity and can be carried for further trials for the clinical treatment of lung cancer
Protein and ligand Preparation: The protein 3D structure or the crystal structure of the target protein i.e. the PD-L1 dimer was taken from the Protein Data Bank (PDB) with the PBD ID: 5J8O [20]

Summary

Introduction

There are 8.8 million recorded deaths of malignant cancer every year according to WHO data and this number keep on increasing which is a clear indication of the threat this disease poses. Studies in the past decade have confirmed that the immune system displays a variety of mechanisms to combat the growth of cancer cells in the body. In order for the cancer cells to grow and develop, the cells have to find ways to repress these immunological mechanisms. One such mechanism used is altering the expression of co-inhibitory and co-stimulatory articulated molecules [1]. Cancer immunotherapy is increasingly being used in recent clinical treatments in order to overcome tumorinducedimmunosuppression.

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Discussion

Conclusion