Abstract

Cancer cells utilize extensive autophagy in effort to adapt to high metabolic stress. This indicates that impairing the high autophagic flux might be an attractive target for cancer therapy. Autophagy related gene 4A (ATG4A) is a key player for autophagy and its inhibition may help in tumor clearance. The present study aims to screen candidate drugs from FDA-approved drugs, a subset of Zinc database, to identify potential ATG4A inhibitors that may have anti-cancer activity. Computer aided drug design approach was applied for the study using the virtual screening tools Raccoon and MGLTools-1.5.6. We have identified the drug Lumacaftor as a potent inhibitor of ATG4A on the basis of computational approaches viz. molecular docking, molecular dynamics simulation and MM/PBSA method. The drug is likely to be a potent regimen candidate to be used as an anti-cancer molecule. However, this potent inhibitor against ATG4A as anti-cancer molecule needs further investigation and validation.

Communicated by Ramaswamy H. Sarma

摘要

癌细胞利用广泛的自噬来努力适应高代谢压力。这表明削弱高自噬通量可能是癌症治疗的一个有吸引力的目标。自噬相关基因4A（ATG4A）是自噬的关键因素，其抑制作用可能有助于清除肿瘤。本研究旨在从FDA批准的药物（锌数据库的子集）中筛选候选药物，以鉴定可能具有抗癌活性的潜在ATG4A抑制剂。使用虚拟筛选工具Raccoon和MGLTools-1.5.6将计算机辅助药物设计方法用于研究。根据计算方法，我们已经确定了Lumacaftor药物是ATG4A的有效抑制剂。分子对接，分子动力学模拟和MM / PBSA方法。该药物可能是用作抗癌分子的有效方案候选者。但是，这种作为抗癌分子的有效抗ATG4A抑制剂需要进一步研究和验证。

由Ramaswamy H.Sarma沟通