Tuesday, December 17, 2019

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

Gao Y, Sungwoo Kim, Lee YI, Lee J; International Journal of Molecular Sciences, 09 Nov 2019, 20(22) DOI: 10.3390/ijms20225601

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.


Drug discovery using the connectivity map (CMap). (A) Target-based drug discovery. (B) Phenotypic drug discovery. (C) CMap-based drug discovery. Gene signature of the biological or pathological state of interest can be used as a query to search through CMap. CMap provides the search result as a list of small molecules scored to predict their probability to mimic or reverse gene expression profiles of the state of interest. Candidate chemicals can be further tested in in vitro cell culture and in vivo animal experiments before proceeding with clinical trials to human subjects.