# Structural reassignment of compound 968, an allosteric glutaminase inhibitor

## TL;DR

This paper corrects the chemical structure of compound 968, an important glutaminase inhibitor used in cancer research.

## Contribution

The paper provides a corrected structural assignment of compound 968 using NMR and X-ray crystallography.

## Key findings

- The previously reported structure of compound 968 is incorrect.
- The true structure of compound 968 is the isomeric benzo[c]acridine.
- Correcting the structure will help in the development of this compound as a drug.

## Abstract

Many cancer cells require extracellular glutamine to meet the energetic, biosynthetic, and redox demands of the proliferative state. Glutaminases catalyze the hydrolysis of glutamine to glutamate, which supports the biosynthesis of amino acids, lipids, and glutathione and can also be oxidatively deaminated to α-ketoglutarate and enter the citric acid cycle. The “glutamine addiction” of cancer cells has made glutaminase an attractive anticancer drug target. Compound 968 is a glutaminase inhibitor that is widely used to probe cancer cells’ dependence on glutaminase activity. Here, we show by NMR spectroscopy and X-ray crystallography that the reported benzo[c]phenanthridine structure of compound 968 is incorrect; its true structure is the isomeric benzo[c]acridine. The structural reassignment of compound 968 will aid the medicinal chemistry development of this important compound.