6-Diazo-5-oxo-L-nor-Leucine (DON) is a glutamine analog that inhibits glutaminases (Ki = 6 μM) and other glutamine-utilizing enzymes, including cytidine triphosphate synthase (CTPS), which uses glutamine in the synthesis of CTP.[1],[2],[3] DON is commonly used in cells or tissues but its use in whole animals is limited by its teratogenicity.[3],[4],[5]
Reference:
[1]. Willis, R.C., and Seegmiller, J.E. The inhibition by 6-diazo-5-oxo-l-norleucine of glutamine catabolism of the cultured human lymphoblast. J.Cell Physiol. 93, 375-382 (1977).
[2]. Thangavelu, K., Chong, Q.Y., Low, B.C., et al. Structural basis for the active site inhibition mechanism of human kidney-type glutaminase (KGA). Sci.Rep. 4, 1-7 (2014).
[3]. Thomas, A.G., Rojas, C., Tanega, C., et al. Kinetic characterization of ebselen, chelerythrine and apomorphine as glutaminase inhibitors. Biochemical and Biophysical Research Communications 438(2), 243-248 (2013).

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