In Silico Research Laboratory, Eminent Biosciences, Mahalakshmi Nagar, Indore - 452010, Madhya Pradesh, India.
3Center of Excellence in Biotechnology Research, College of Science, King Saud University, Riyadh, Saudi Arabia.
Curr Comput Aided Drug Des. 2021;17(3):387-401. doi: 10.2174/1573409916666200504105249.
Non-Small Cell Lung Cancer (NSCLC) alone is the leading cause of deaths worldwide. ROS1 is a receptor tyrosine kinase (RTK), eminently recognized as the stereotyped oncogenic driver. These RTKs trigger an array of physiological regulations via cellular signal transduction pathways, which are crucial for cancer development. This attributed ROS1 as an appealing and potential target towards the targeted cancer therapy. The present research aims to propound out an effective contemporary inhibitor for targeting ROS1 with a high affinity.
Molegro Virtual Docker (MVD) provided a flexible docking platform to find out the bestestablished drug as an inhibitor for targeting ROS1. A similarity search was accomplished against the PubChem database to acquire the corresponding inhibitor compounds regarding the Entrectinib (Pub- Chem ID: 25141092). These compounds were docked to procure the high-affinity inhibitor for the target protein via virtual screening. A comparative study between the control molecule (PubChem ID: 25141092)and the virtual screened compound(PubChem ID-25175866) was performed for the relative analysis of their salient features, which involved pharmacophore mapping, ADMET profiling, and BOILED-Egg plot.
The virtual screened compound (PubChem ID-25175866) possesses the lowest rerank score (-126.623), and the comparative ADMET analysis also shows that it is a potential and effective inhibitor for ROS1 among the selected inhibitors.
The present study provided a scope for the ROS1 inhibitor as significant prevention for nonsmall cell lung cancer (NSCLC). It can be upheld for future studies as a promising support via in vivo studies.
非小细胞肺癌（NSCLC）是全球主要的死亡原因。ROS1 是一种受体酪氨酸激酶（RTK），被认为是典型的致癌驱动基因。这些 RTKs 通过细胞信号转导途径触发一系列生理调节，对癌症的发展至关重要。这使得 ROS1 成为靶向癌症治疗的一个有吸引力和潜在的靶点。本研究旨在提出一种针对 ROS1 的有效现代抑制剂，具有高亲和力。
Molegro Virtual Docker（MVD）提供了一个灵活的对接平台，以找到针对 ROS1 的最佳已建立药物作为抑制剂。对 PubChem 数据库进行相似性搜索，以获取与恩曲替尼（PubChem ID：25141092）相对应的抑制剂化合物。通过虚拟筛选，这些化合物被对接以获得靶蛋白的高亲和力抑制剂。对对照分子（PubChem ID：25141092）和虚拟筛选化合物（PubChem ID-25175866）进行比较研究，以分析它们的显著特征，包括药效团映射、ADMET 分析和 BOILED-Egg 图。
虚拟筛选化合物（PubChem ID-25175866）具有最低的重新排名分数（-126.623），比较 ADMET 分析也表明，它是所选抑制剂中针对 ROS1 的潜在有效抑制剂。
本研究为 ROS1 抑制剂作为非小细胞肺癌（NSCLC）的重要预防措施提供了一个研究方向。它可以通过体内研究为未来的研究提供有前途的支持。
