A comprehensive analysis method for target proteins that bind compounds

December 6, 2019

Focused on changes in protein thermostability due to binding

A joint research team from RIKEN CSRS and the Institute of Microbial Chemistry have developed a method to search for compounds that bind to proteins (target proteins) by observing thermodynamic stability changes in proteins. The method was successfully used to identify candidate target proteins for compounds that show anti-cancer activity.

The team built a comprehensive analysis method by combining cellular thermal shift assay (CETSA) and proteome analysis based on two-dimensional gel electrophoresis, called 2DE-CETSA, to measure changes in thermostability when compounds bind to a protein.

Using a human cancer cells, researchers identified PKM2 (a glycolytic metabolic enzyme) as a candidate target protein for NPD10084, a compound that inhibits cell proliferation in colorectal cancer cells.

These research results are expected to contribute to the identification of target proteins for bioactive compounds found during phenotypic screening, and to the elucidation of mechanisms of action of those compounds.

Original article
Cell Chemical Biology doi:10.1016/j.chembiol.2019.11.010
Ikuko Nagasawa, Makoto Muroi, Makoto Kawatani, Tomokazu Ohishi, Shun-ichi Ohba, Manabu Kawada, Hiroyuki Osada,
"Identification of a small compound targeting PKM2-regulated signaling using 2D gel electrophoresis-based proteome-wide CETSA".
Ikuko Nagasawa; Special Postdoctoral Researcher
Makoto Muroi; Senior Research Scientist
Makoto Kawatani; Senior Research Scientist
Hiroyuki Osada; Group Director
Chemical Biology Research Group