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Are Enantiomer of Chemical Probes Good Negative Control?

Tang Shiting; Schapira Matthieu

Chemical probes are drug-like compounds that bind potently and selectively to a protein target. When there is a chiral center in the compound, a common practice is to purify and test both enantiomers. Sometimes (often) enantiomer A is active and B is inactive or far less potent. When this is the case, enantiomer A is declared the chemical probe, while enantiomer B is used as a negative control . But if enantiomer A is active against unknown off-targets, enantiomer B may be inactive against these off-targets, which would be a serious problem. The project is to systematically evaluate how often enantiomer B is inactive against protein X if enantiomer A is active against the same target. 

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