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Target id: 2891

Nomenclature: glutaminase

Family: Glutaminases

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 669 2q32.2 GLS glutaminase
Mouse - 674 1 26.86 cM Gls glutaminase
Rat - 674 9q22 Gls glutaminase
Gene and Protein Information Comments
The table above provides details of human isoform 1. hGLS isoform 2 is shorter (598aa) and has a distinct C-terminus, compared to isoform 1. We also show the longer isoforms of the rat and mouse Gls proteins.
Previous and Unofficial Names Click here for help
K-glutaminase | GLS1 | glutaminase 1 | GAC | L-glutamine amidohydrolase | glutaminase kidney isoform | Gls
Database Links Click here for help
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
RefSeq Nucleotide
RefSeq Protein

Download all structure-activity data for this target as a CSV file go icon to follow link

Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
telaglenastat Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Inhibition 8.3 pIC50 6
pIC50 8.3 (IC50 5x10-9 M) [6]
IPN60090 Small molecule or natural product Hs Inhibition 7.5 pIC50 7
pIC50 7.5 (IC50 3.1x10-8 M) [7]
General Comments
Glutaminase is the first enzyme in the glutaminolysis pathway. GLS gene products are expressed in the kidney (where it is involved in maintaining acid-base balance), in the brain (where it is essential for synthesizing the brain neurotransmitter glutamate), in cardiac muscle, skeletal muscle and pancreas but is NOT expressed in the liver. Glutaminase C (GAC) and kidney-type glutaminase (KGA) are splice variants of the GLS gene, produced by tissue-specific alternative splicing of a single pre-mRNA [1,3].

Glutaminase activity is being targeted for pharmacological inhibition as a potential anti-cancer treatment [2,4-5], based in part on the discovery that the GAC isoform is the predominant isoform expressed by breast cancer cells which are highly dependent on glutaminolysis for growth and survival [1].


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1. Cassago A, Ferreira AP, Ferreira IM, Fornezari C, Gomes ER, Greene KS, Pereira HM, Garratt RC, Dias SM, Ambrosio AL. (2012) Mitochondrial localization and structure-based phosphate activation mechanism of Glutaminase C with implications for cancer metabolism. Proc Natl Acad Sci USA, 109 (4): 1092-7. [PMID:22228304]

2. Chakrabarti G, Moore ZR, Luo X, Ilcheva M, Ali A, Padanad M, Zhou Y, Xie Y, Burma S, Scaglioni PP et al.. (2015) Targeting glutamine metabolism sensitizes pancreatic cancer to PARP-driven metabolic catastrophe induced by ß-lapachone. Cancer Metab, 3: 12. [PMID:26462257]

3. Elgadi KM, Meguid RA, Qian M, Souba WW, Abcouwer SF. (1999) Cloning and analysis of unique human glutaminase isoforms generated by tissue-specific alternative splicing. Physiol Genomics, 1 (2): 51-62. [PMID:11015561]

4. Gross MI, Demo SD, Dennison JB, Chen L, Chernov-Rogan T, Goyal B, Janes JR, Laidig GJ, Lewis ER, Li J et al.. (2014) Antitumor activity of the glutaminase inhibitor CB-839 in triple-negative breast cancer. Mol Cancer Ther, 13 (4): 890-901. [PMID:24523301]

5. Jacque N, Ronchetti AM, Larrue C, Meunier G, Birsen R, Willems L, Saland E, Decroocq J, Maciel TT, Lambert M et al.. (2015) Targeting glutaminolysis has antileukemic activity in acute myeloid leukemia and synergizes with BCL-2 inhibition. Blood, 126 (11): 1346-56. [PMID:26186940]

6. Li J, Chen L, Goyal B, Laidig G, Stanton TF, Sjogren EB. (2013) Heterocyclic inhibitors of glutaminase. Patent number: US 8604016 B2. Assignee: Calithera Biosciences Inc.. Priority date: 21/11/2011. Publication date: 10/12/2013.

7. Soth MJ, Le K, Di Francesco ME, Hamilton MM, Liu G, Burke JP, Carroll CL, Kovacs JJ, Bardenhagen JP, Bristow CA et al.. (2020) Discovery of IPN60090, a Clinical Stage Selective Glutaminase-1 (GLS-1) Inhibitor with Excellent Pharmacokinetic and Physicochemical Properties. J Med Chem, 63 (21): 12957-12977. [PMID:33118821]

How to cite this page Glutaminases: glutaminase. Last modified on 06/06/2023. Accessed on 20/05/2024. IUPHAR/BPS Guide to PHARMACOLOGY,