Cellular Stress-Modulating Drugs Can Potentially Be Identified by in Silico Screening with Connectivity Map (CMap)

• Published in: International journal of molecular sciences Vol. 20; no. 22; p. 5601
• Main Authors: Gao, Yurong, Kim, Sungwoo, Lee, Yun-Il, Lee, Jaemin
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 09.11.2019; MDPI
• Subjects: Aging; Amyotrophic lateral sclerosis; Animal models; Animals; Cancer; Cell Hypoxia - drug effects; Cell proliferation; cellular stress; Cellular stress response; cmap; Computer Simulation; connectivity map; Diabetes; Disease; drug discovery; Drug Discovery - methods; Drugs; Endoplasmic reticulum; endoplasmic reticulum stress; Endoplasmic Reticulum Stress - drug effects; er stress; Gene expression; Heat shock; Heat-Shock Response - drug effects; Homeostasis; HSF1 protein; Hsp70 protein; Humans; hypoxia; Insulin resistance; Kinases; Life span; Localization; Metabolic disorders; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondria - pathology; mitochondrial stress; Neural networks; Oxidative stress; Oxidative Stress - drug effects; Parkinson's disease; Pharmaceutical industry; Protein folding; Proteins; Quality control; Review; Transcription factors; Tumor cells; Tumors; Unfolded Protein Response - drug effects; hypoxia; drug discovery; CMap; ER stress; connectivity map; mitochondrial stress; endoplasmic reticulum stress; oxidative stress; cellular stress
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20225601

Accompanied by increased life span, aging-associated diseases, such as metabolic diseases and cancers, have become serious health threats. Recent studies have documented that aging-associated diseases are caused by prolonged cellular stresses such as endoplasmic reticulum (ER) stress, mitochondrial stress, and oxidative stress. Thus, ameliorating cellular stresses could be an effective approach to treat aging-associated diseases and, more importantly, to prevent such diseases from happening. However, cellular stresses and their molecular responses within the cell are typically mediated by a variety of factors encompassing different signaling pathways. Therefore, a target-based drug discovery method currently being used widely (reverse pharmacology) may not be adequate to uncover novel drugs targeting cellular stresses and related diseases. The connectivity map (CMap) is an online pharmacogenomic database cataloging gene expression data from cultured cells treated individually with various chemicals, including a variety of phytochemicals. Moreover, by querying through CMap, researchers may screen registered chemicals in silico and obtain the likelihood of drugs showing a similar gene expression profile with desired and chemopreventive conditions. Thus, CMap is an effective genome-based tool to discover novel chemopreventive drugs.