Page last updated: 2024-11-13

glutaminase

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Cross-References

ID SourceID
PubMed CID72950407
CHEMBL ID4081588
SCHEMBL ID16751074
SCHEMBL ID16735736
MeSH IDM0009380

Synonyms (25)

Synonym
glutaminase
SCHEMBL16751074
SCHEMBL16735736
1542132-88-6
methyl (s,e)-7-((1-(2-((2-ethylbutyl)amino)-2-oxoethyl)-2-oxo-1,2-dihydropyridin-3-yl)amino)-6-(1-methyl-1h-imidazole-5-carboxamido)-7-oxohept-2-enoate
gtpl12802
bdbm50245478
methyl (e,6s)-7-[[1-[2-(2-ethylbutylamino)-2-oxoethyl]-2-oxopyridin-3-yl]amino]-6-[(3-methylimidazole-4-carbonyl)amino]-7-oxohept-2-enoate
t4sr539ykf ,
(2e,6s)-7-((1-(2-((2-ethylbutyl)amino)-2-oxoethyl)-1,2-dihydro-2-oxo-3-pyridinyl)amino)-6-(((1-methyl-1h-imidazol-5-yl)carbonyl)amino)-7-oxo-2-heptenoic acid methyl ester
methyl (2e,6s)-7-((1-(2-((2-ethylbutyl)amino)-2-oxoethyl)-1,2-dihydro-2-oxo-3-pyridinyl)amino)-6-(((1-methyl-1h-imidazol-5-yl)carbonyl)amino)-7-oxo-2-heptenoate
2-heptenoic acid, 7-((1-(2-((2-ethylbutyl)amino)-2-oxoethyl)-1,2-dihydro-2-oxo-3-pyridinyl)amino)-6-(((1-methyl-1h-imidazol-5-yl)carbonyl)amino)-7-oxo-, methyl ester, (2e,6s)-
unii-t4sr539ykf
methyl (e,6s)-7-((1-(2-(2-ethylbutylamino)-2-oxo-ethyl)-2-oxo-3-pyridyl)amino)-6-((3-methylimidazole-4-carbonyl)amino)-7-oxo-hept-2-enoate
CS-0015432
HY-19359
CHEMBL4081588 ,
zed-1227
zed1227
MS-29784
methyl (2e,6s)-7-[[1-[2-[(2-ethylbutyl)amino]-2-oxoethyl]-1,2-dihydro-2-oxo-3-pyridinyl]amino]-6-[[(1-methyl-1h-imidazol-5-yl)carbonyl]amino]-7-oxo-2-heptenoate
tak-227
2-heptenoic acid, 7-[[1-[2-[(2-ethylbutyl)amino]-2-oxoethyl]-1,2-dihydro-2-oxo-3-pyridinyl]amino]-6-[[(1-methyl-1h-imidazol-5-yl)carbonyl]amino]-7-oxo-, methyl ester, (2e,6s)-
AKOS040742843
EX-A7845R

Research Excerpts

Overview

Glutaminase 1 (GLS1) is a critical enzyme involved in several cellular processes. overexpression of GLS1 has been linked to the development and progression of cancer. L-Glutaminase is considered to be an important industrial enzyme in both the pharmaceutical and food industries.

ExcerptReferenceRelevance
"Glutaminase 1 (GLS) is a therapeutic target for breast cancer; although GLS inhibitors have been developed, only a few subjects responded well to the therapy. "( Prognostic value of glutaminase 1 in breast cancer depends on H3K27me3 expression and menopausal status.
Chen, QX; Guan, JX; Huang, ZY; Li, YL; Liang, ZZ; Ren, ZF; Tang, LY; Weng, ZJ; Yang, YZ; Zhang, XF; Zhou, M, 2022
)
2.49
"Glutaminase is a key enzyme, which supports elevated dependency of tumors on glutamine-dependent biosynthesis of metabolic intermediates. "( Telaglenastat plus Everolimus in Advanced Renal Cell Carcinoma: A Randomized, Double-Blinded, Placebo-Controlled, Phase II ENTRATA Trial.
Akella, L; Bendell, J; Emamekhoo, H; Fan, AC; Gartrell, BA; Goodman, OB; Hsieh, JJ; Hussain, A; Kalebasty, AR; Lee, CH; Liu, S; Matrana, M; McCune, S; Motzer, R; Nikolinakos, PG; Orford, K; Parmar, H; Patel, V; Percent, I; Shaheen, M; Tannir, NM; Vaishampayan, U; Zakharia, Y; Zhang, Z, 2022
)
2.16
"Glutaminase is a key enzyme that fuels tumor growth by converting glutamine to glutamate."( Efficacy and Safety of Telaglenastat Plus Cabozantinib vs Placebo Plus Cabozantinib in Patients With Advanced Renal Cell Carcinoma: The CANTATA Randomized Clinical Trial.
Agarwal, N; Akella, L; Appleman, LJ; Davis, N; Escudier, B; Figlin, R; Gandhi, S; Geynisman, DM; Goodman, O; Iacovelli, R; Jain, RK; Lawrence, NJ; Lee, RJ; McGregor, B; Mellado, B; Motzer, R; Orford, K; Porta, C; Powles, T; Sepúlveda Sánchez, JM; Stadler, WM; Tannir, NM, 2022
)
1.44
"Glutaminase-1 (GLS1) is a critical enzyme involved in several cellular processes, and its overexpression has been linked to the development and progression of cancer. "( Targeting glutaminase 1 (GLS1) by small molecules for anticancer therapeutics.
Chen, Y; Gao, J; Li, Y; Lin, C; Tan, L; Wu, F; Zhang, J, 2023
)
2.76
"Glutaminase (GLS), which is a key enzyme in the glutamine metabolism, was identified and validated as a direct target of miR-181-5p in ESCA cells."( LncRNA PVT1 Confers Cisplatin Resistance of Esophageal Cancer Cells through Modulating the miR-181a-5p-Glutaminase (GLS) Axis.
Chen, Z; Hu, J; Huang, L; Wang, Q; Xu, G, 2023
)
1.85
"L-glutaminase is a hydrolytic enzyme with wide biotechnological applications. "( Optimization of L-glutaminase production by Monascus ruber URM 8542 isolated from ice cream industrial effluent.
Barbosa, RDN; da Conceição, EM; de Oliveira da Silva, LA; de Oliveira Silva, W; de Oliveira, NT; de Souza-Motta, CM; do Nascimento, SS, 2023
)
1.97
"Glutaminase (GLS1) is a cancer energy metabolism protein which plays a predominant role in cell growth and proliferation. "( Development and Characterization of a Fluorescent Probe for GLS1 and the Application for High-Throughput Screening of Allosteric Inhibitors.
Bian, J; Ding, H; Han, J; Kuang, Z; Li, L; Li, Z; Luan, H; Luo, C; Meng, Y; Wang, J; Xu, P; Xu, X, 2019
)
1.96
"L-Glutaminase is considered to be an important industrial enzyme in both the pharmaceutical and food industries, especially for producing functional glutamyl compounds, such as l-theanine. "( Permeabilization and immobilization of whole-cell Pseudomonas nitroreducens SP.001 to improve its l-glutaminase performance.
Hua, Y; Jiang, B; Luo, Y; Shen, X; Shuai, Y; Zhang, T, 2021
)
1.56
"Glutaminase (GLS) is an important gene in the glutamine-dependent acid resistance (AR) system; however, its role in T."( RNAi-mediated silencing of Trichinella spiralis glutaminase results in reduced muscle larval infectivity.
Gao, Y; Han, C; Li, W; Li, X; Meng, S; Meng, X; Song, M; Wang, S; Yang, X, 2021
)
1.6
"Glutaminase is an important target that is often over expressed in neurodegenerative and lifestyle related diseases but few effective inhibitors of this enzyme have yet reached clinical trials. "( Glutaminase inhibitory activities of pentacyclic triterpenes isolated from
Inagaki, M; Shimada, A; Ueno, H, 2022
)
3.61
"l-glutaminases is an important industrial enzyme which finds potential applications in different sectors ranging from therapeutic to food industry. "( Recent developments in l-glutaminase production and applications - An overview.
Abraham, A; Beevi, US; Binod, P; Madhavan, A; Mathew, AK; Pandey, A; Sindhu, R; Singh, SP; Sukumaran, RK, 2017
)
1.48
"Glutaminase C is a key metabolic enzyme, which is unregulated in many cancer systems and believed to play a central role in the Warburg effect, whereby cancer cells undergo changes to an altered metabolic profile. "( Small angle X-ray scattering studies of mitochondrial glutaminase C reveal extended flexible regions, and link oligomeric state with enzyme activity.
Cerione, RA; Gillilan, RE; Li, Y; Møller, M; Nielsen, SS; Petoukhov, MV; Ramachandran, S; Streicher, W; Tria, G; Vestergaard, B, 2013
)
2.08
"Glutaminase 2 (Gls2) is a p53 target gene and is known to play an important role in energy metabolism. "( Epigenetic silencing of glutaminase 2 in human liver and colon cancers.
Cao, J; Chen, L; Chen, M; Shen, HM; Wang, C; Xia, D; Zhang, J; Zhong, Y, 2013
)
2.14
"Glutaminase is a metabolic enzyme responsible for glutaminolysis, a process harnessed by cancer cells to feed their accelerated growth and proliferation. "( Structural basis for the active site inhibition mechanism of human kidney-type glutaminase (KGA).
Chong, QY; Low, BC; Sivaraman, J; Thangavelu, K, 2014
)
2.07
"Glutaminase (GLS1) is a mitochondrial enzyme that converts glutamine to glutamate."( Expression of glutaminase is upregulated in colorectal cancer and of clinical significance.
Huang, F; Lv, Q; Ma, H; Zhang, Q; Zhang, T, 2014
)
1.48
"Glutaminase (GLS1) is a key enzyme that converts glutamine to glutamate."( Elevated expression of glutaminase confers glucose utilization via glutaminolysis in prostate cancer.
Gao, L; Pan, T; Qian, W; Shen, G; Tu, Z; Wen, H; Wu, G; Xie, S; Yang, J; Zhou, Y, 2015
)
1.45
"The glutaminase subunit is a glutamine amidotransferase that hydrolyzes glutamine and channels ammonia to the synthase active site."( Crystal structures capture three states in the catalytic cycle of a pyridoxal phosphate (PLP) synthase.
Brown, WC; Harms, E; Smith, AM; Smith, JL, 2015
)
0.9
"Glutaminase (GLS) is an enzyme of the glutamate-glutamine cycle that converts glutamine into glutamate for neurotransmission and is implicated in producing elevated levels of glutamate in central and peripheral terminals."( Glutaminase Increases in Rat Dorsal Root Ganglion Neurons after Unilateral Adjuvant-Induced Hind Paw Inflammation.
Hoffman, EM; Miller, KE; Schechter, R; Zhang, Z, 2016
)
2.6
"Glutaminase (GLS) is a mitochondrial enzyme that catalyzes the conversion of Gln to glutamate."( Inhibiting glutaminase in acute myeloid leukemia: metabolic dependency of selected AML subtypes.
Baran, N; Cai, T; Chan, SM; Davis, RE; DiNardo, C; Flores, ER; Gonzalez, D; Haferlach, T; Jacamo, R; Konoplev, S; Konopleva, M; Li, W; Lodi, A; Ma, H; Majeti, R; Matre, P; Qi, Y; Samudio, I; Schimmer, AD; Su, X; Sweeney, SR; Tiziani, S; Velez, J; Wang, T, 2016
)
1.55
"Glutaminase is a mitochondrial protein, but was found to be released into the cytosol and extracellular space following infection."( In vitro glutaminase regulation and mechanisms of glutamate generation in HIV-1-infected macrophage.
Curthoys, N; Erdmann, N; Herek, S; Huang, Y; Tian, C; Zhao, J; Zheng, J, 2009
)
1.49
"Glutaminase is a multifunctional enzyme encoded by gene Gls involved in energy metabolism, ammonia trafficking and regeneration of neurotransmitter glutamate. "( Network of brain protein level changes in glutaminase deficient fetal mice.
Bae, N; Li, L; Lubec, G; Rayport, S; Wang, Y, 2013
)
2.1
"Glutaminase is a hematotoxic anti-tumor agent, and copper-ATP complex (Cu-ATP) is both anti-neoplastic and hematostimulatory. "( Anti-tumor efficacy of glutaminase-copper-ATP combination in mice bearing Ehrlich ascites carcinoma.
Maity, P; Pal, S, 1994
)
2.04
"Glutaminase (EC 3.5.1.2) is a key enzyme in rapidly proliferating cells. "( Ehrlich ascites tumor cells expressing anti-sense glutaminase mRNA lose their capacity to evade the mouse immune system.
Alonso, FJ; Arenas, M; Lobo, C; Márquez, J; Ruiz-Bellido, MA; Segura, JA, 2001
)
2.01
"Glutaminase is a key enzyme in the metabolism of glutamine, an important fuel for normal and neoplastic cells."( Effect of aging on the glutaminase activity of neoplastic and immune tissues.
Curi, R; Fava-de-Moraes, F; Homem-de-Bittencourt Júnior, PI; Nunes, FD; Santos, MF, 1992
)
1.32

Effects

Glutaminase has a central role in intestinal metabolism. The products of the reaction catalyzed by glutaminase can be transaminated, catabolized to yield energy or used for the biosynthesis of pyrimidine nucleotides. Glutaminases have a relatively high affinity for L-asparagine and L-glutamine.

Glutaminase 1 (GLS1) has been viewed as a promising target in the glutamine metabolism pathway for the treatment of malignant tumors. The purified preparation is estimated to contain about 40% glutaminase B. Glutamin enzyme has been proposed to provide the urea cycle with ammonia.

ExcerptReferenceRelevance
"L-glutaminase has a significant efficiency against Hep-G2 cell (IC50, 6.8 μg/mL) and HeLa cells (IC50, 8.3 μg/mL), while the growth of MCF-7 cells was not affected."( Kinetic properties of Streptomyces canarius L- Glutaminase and its anticancer efficiency.
Reda, FM,
)
0.95
"Glutaminase has a central role in intestinal metabolism: the products of the reaction catalyzed by glutaminase can be transaminated, catabolized to yield energy or used for the biosynthesis of pyrimidine nucleotides."( The role of glutaminase in the small intestine.
Hall, JC; Heel, K; Kong, SE; McCauley, R,
)
1.23
"The glutaminase-asparaginase has a relatively high affinity for L-asparagine (Km=1.5 X 10(-5) M) and L-glutamine (Km=2.2 X 10(-5) M) and has a molecular weight of approximately 156,000 the subunit molecular weight being approximately 39,000."( Purification and properties of L-glutaminase-L-asparaginase from Pseudomonas acidovorans.
Brear, DR; Davidson, L; Hawkins, J; Kitto, GB; Wingard, P, 1977
)
1.02
"Glutaminase 1 (GLS1) has been viewed as a promising target in the glutamine metabolism pathway for the treatment of malignant tumors."( Design, synthesis, and biological evaluation of novel glutaminase 1 allosteric inhibitors with an alkane chain tail group.
Bian, J; Chang, X; Li, Z; Wang, J; Wang, M; Xu, X; Zhang, D; Zhang, Y, 2023
)
1.88
"Glutaminase 2 (GLS2) has been reported as a tumor suppressor."( Glutaminase 2 stabilizes Dicer to repress Snail and metastasis in hepatocellular carcinoma cells.
Chen, CK; Chen, MW; Chien, MH; Hsiao, M; Hua, KT; Jeng, YM; Kuo, KT; Kuo, ML; Kuo, TC; Lee, WJ; Yu, P, 2016
)
2.6
"Glutaminase has been proposed to provide the urea cycle with ammonia [Häussinger and Gerok (1983) Eur."( Hepatic glutaminase mRNA is confined to part of the urea cycle domain in the adult rodent liver lobule.
de Boer, PA; Dingemanse, MA; Lamers, WH; Moorman, AF; Watford, M, 1994
)
1.44
"Glutaminase B has been purified 6,000-fold and the purified preparation is estimated to contain about 40% glutaminase B."( Regulation of glutaminase B in Escherichia coli. I. Purification, properties, and cold lability.
Davis, JN; Prusiner, S; Stadtman, ER, 1976
)
1.34
"Glutaminase has been considered to be a synthesizing enzyme of transmitter glutamate in pyramidal neurons of the cerebral cortex. "( Paucity of glutaminase-immunoreactive nonpyramidal neurons in the rat cerebral cortex.
Kaneko, T; Mizuno, N; Nakaya, Y, 1992
)
2.12

Actions

Glutaminase plays an important role in carcinogenesis and cancer cell growth. Glutaminases catalyze the deamidation of glutamine to glutamic acid. targeting GLU metabolism by inhibiting GLS has attracted interest as a potential cancer management strategy.

ExcerptReferenceRelevance
"Glutaminase (GLS) plays a crucial role in promoting cell metabolism for cancer cell growth; targeting GLU metabolism by inhibiting GLS has attracted interest as a potential cancer management strategy."( Targeting Glutaminase by Natural Compounds: Structure-Based Virtual Screening and Molecular Dynamics Simulation Approach to Suppress Cancer Progression.
Hoque, M; Khan, AU; Khan, MI; Suhail, M; Tabrez, S; Zughaibi, TA, 2022
)
1.85
"Glutaminase plays an important role in carcinogenesis and cancer cell growth. "( Molecular modeling and LC-MS-based metabolomics of a glutamine-valproic acid (Gln-VPA) derivative on HeLa cells.
Correa-Basurto, J; Estrada-Pérez, A; Fragoso-Vázquez, MJ; Fromager, B; Luna-Palencia, GR; Méndez-Luna, D; Rosales-Hernández, MC; Vásquez-Moctezuma, I, 2021
)
2.06
"Glutaminases catalyze glutaminolysis in mitochondria, regulating oxidative phosphorylation, redox status and cell metabolism for tumour growth."( Glutaminases regulate glutathione and oxidative stress in cancer.
Campos-Sandoval, JA; de Los Santos-Jiménez, J; Márquez, J; Matés, JM, 2020
)
2.72
"Glutaminases catalyze the deamidation of glutamine to glutamic acid, and this unique ability forms the basis of their applications in various industries such as pharmaceutical and food organizations."( Recent advances in microbial glutaminase production and applications-a concise review.
Amobonye, A; Pillai, S; Singh, S, 2019
)
1.53
"Glutaminase plays a critical role in the generation of glutamate, a key excitatory neurotransmitter in the CNS. "( Small molecule glutaminase inhibitors block glutamate release from stimulated microglia.
Bressler, J; Kaufmann, W; O'Driscoll, CM; Rojas, CJ; Slusher, BS; Thomas, AG, 2014
)
2.2
"etli glutaminase also plays a role in maintaining the balance between glutamate and glutamine, as shown by the accumulation of glutamine and the low glutamate content of the mutant under different growth conditions."( The role of glutaminase in Rhizobium etli: studies with a new mutant.
Calderón, J; Du Pont, G; Durán, S; Huerta-Zepeda, A, 1995
)
1.13

Treatment

ExcerptReferenceRelevance
"Glutaminase treatment increased DPPH-scavenging capacity, foaming capacity and stability of SPI."( Modification of soy protein isolate by glutaminase for nanocomplexation with curcumin.
Cui, C; Dong, K; Sun-Waterhouse, D; Wang, W; Xiang, H, 2018
)
1.47

Toxicity

ExcerptReferenceRelevance
" A 90-day study of PG, conducted in Sprague-Dawley rats, showed no adverse effects due to the enzyme up to dose levels of 2500 mg/kg-bw/day (NOAEL)."( Studies on the non-pathogenicity of Chryseobacterium proteolyticum and on the safety of the enzyme: protein-glutaminase.
Mizutani, A; Scheuplein, RJ; Yamaguchi, S, 2007
)
0.55
"As a highly toxic environmental pollutant, methylmercury (MeHg) can cause neurotoxicity in animals and humans."( Effect of grape seed proanthocyanidin extracts on methylmercury-induced neurotoxicity in rats.
Deng, Y; Liu, W; Wei, Y; Xu, B; Xu, Z; Yang, H, 2012
)
0.38
" Potential adverse effects of air pollutants to the central nervous system (CNS) have raised concerns, but whether PM2."( Macrophages treated with particulate matter PM2.5 induce selective neurotoxicity through glutaminase-mediated glutamate generation.
Chen, Q; Ding, W; Huang, Y; Liu, F; Rui, W; Wu, B; Zhang, F; Zheng, JC, 2015
)
0.64
" megaterium, the most desirable properties for safe clinical applications."( Characterization of novel L-asparaginases having clinically safe profiles from bacteria inhabiting the hemolymph of the crab, Scylla serrata (Forskål, 1775).
Amala, PV; Anusree, VN; Kishor, TG; Lailaja, VP; Reshma, KJ; Sanil, NK; Sumithra, TG, 2022
)
0.72
" Treatment-emergent adverse event (TEAE) rates were similar between arms."( Efficacy and Safety of Telaglenastat Plus Cabozantinib vs Placebo Plus Cabozantinib in Patients With Advanced Renal Cell Carcinoma: The CANTATA Randomized Clinical Trial.
Agarwal, N; Akella, L; Appleman, LJ; Davis, N; Escudier, B; Figlin, R; Gandhi, S; Geynisman, DM; Goodman, O; Iacovelli, R; Jain, RK; Lawrence, NJ; Lee, RJ; McGregor, B; Mellado, B; Motzer, R; Orford, K; Porta, C; Powles, T; Sepúlveda Sánchez, JM; Stadler, WM; Tannir, NM, 2022
)
0.72

Pharmacokinetics

ExcerptReferenceRelevance
"Cellular pharmacodynamic assays are crucial aspects of lead optimization programs in drug discovery."( New Platform for Label-Free, Proximal Cellular Pharmacodynamic Assays: Identification of Glutaminase Inhibitors Using Infrared Matrix-Assisted Laser Desorption Electrospray Ionization Mass Spectrometry.
Bruckner, BG; Elsen, NL; Fontaine, DA; Gopalakrishnan, SM; Panchal, SC; Pu, F; Radosevich, AJ; Williams, JD, 2023
)
1.13

Compound-Compound Interactions

ExcerptReferenceRelevance
" Importantly, tracking time-dependent growth after drug treatment demonstrated that a KGA allosteric inhibitor alone failed to completely inhibit cancer cell growth, but a drug combination was able to provide complete inhibition in cell-based assays that translated well in in vivo animal experiments."( The EZMTT cell proliferation assay provides precise measurement for drug combinations and better correlation between in vitro and in vivo efficacy.
Bai, R; Ruan, B; Rui, J; Su, W; Xu, N; Yin, J; Yu, Y, 2020
)
0.56

Bioavailability

CB-839 is a potent, selective, orally bioavailable inhibitor of glutaminase. Has activity in Triple receptor-Negative Breast Cancer (TNBC) cell lines and evidence of efficacy in advanced TNBC patients.

ExcerptReferenceRelevance
" CB-839 is a potent, selective, and orally bioavailable inhibitor of both splice variants of glutaminase (KGA and GAC)."( Antitumor activity of the glutaminase inhibitor CB-839 in triple-negative breast cancer.
Bennett, MK; Chen, L; Chernov-Rogan, T; Demo, SD; Dennison, JB; Goyal, B; Gross, MI; Janes, JR; Laidig, GJ; Lewis, ER; Li, J; Mackinnon, AL; Parlati, F; Rodriguez, ML; Shwonek, PJ; Sjogren, EB; Stanton, TF; Wang, T; Yang, J; Zhao, F, 2014
)
0.92
" Inhibition of glutaminase by allosteric GLS inhibitor bis-2-(5-phenylacetamido-1, 2, 4-thiadiazol-2-yl) ethyl sulfide or by novel, potent, orally bioavailable GLS inhibitor CB-839 reduced intracellular glutamate levels and inhibited growth of AML cells."( Inhibiting glutaminase in acute myeloid leukemia: metabolic dependency of selected AML subtypes.
Baran, N; Cai, T; Chan, SM; Davis, RE; DiNardo, C; Flores, ER; Gonzalez, D; Haferlach, T; Jacamo, R; Konoplev, S; Konopleva, M; Li, W; Lodi, A; Ma, H; Majeti, R; Matre, P; Qi, Y; Samudio, I; Schimmer, AD; Su, X; Sweeney, SR; Tiziani, S; Velez, J; Wang, T, 2016
)
1.18
" However, the bioavailability of the vitamin in the edible portions of the commonly consumed plants is insufficient to meet the daily recommended doses."( Overexpression of PDX-II gene in potato (Solanum tuberosum L.) leads to the enhanced accumulation of vitamin B6 in tuber tissues and tolerance to abiotic stresses.
Bagri, DS; Kumar, A; Upadhyaya, CP; Upadhyaya, DC, 2018
)
0.48
" In contrast to previous studies, treatment of autochthonous tumour-bearing animals with Telaglenastat (CB-839), an orally bioavailable GLS inhibitor, successfully inhibits undifferentiated pleomorphic sarcoma (UPS) tumour growth."( Targeting glutamine metabolism slows soft tissue sarcoma growth.
Burrows, M; Finan, JM; Gade, TPF; Gong, YY; Huangyang, P; Khare, S; Lee, P; Malik, D; Nissim, I; Perkons, N; Rhoades, S; Simon, MC; Weljie, AM, 2020
)
0.56
" CB-839 is a potent, selective, orally bioavailable inhibitor of glutaminase that has activity in Triple receptor-Negative Breast Cancer (TNBC) cell lines and evidence of efficacy in advanced TNBC patients."( Pyruvate anaplerosis is a mechanism of resistance to pharmacological glutaminase inhibition in triple-receptor negative breast cancer.
Baguley, BC; Dechaume, AL; Katt, WP; Leung, EY; Murray, PM; Singleton, DC, 2020
)
1.03
" However, these inhibitors have variable efficacy, specificity and bioavailability in research and clinical settings, implying the need for novel and improved GLS inhibitors."( Identification and characterization of a novel glutaminase inhibitor.
Cederkvist, H; Kolan, SS; Sener, Z; Skålhegg, BS; Wik, JA, 2022
)
0.98
" We found that RCC cells are highly dependent on glutamine for proliferation, and this dependence strongly correlated with sensitivity to telaglenstat (CB-839), an investigational, first-in-class, selective, orally bioavailable GLS inhibitor."( The glutaminase inhibitor telaglenastat enhances the antitumor activity of signal transduction inhibitors everolimus and cabozantinib in models of renal cell carcinoma.
Chen, J; Dang, R; Emberley, E; Gross, M; Huang, T; Li, W; MacKinnon, A; Pan, A; Parlati, F; Singh, D; Sotirovska, N; Steggerda, SM; Wang, T, 2021
)
1.18

Dosage Studied

ExcerptRelevanceReference
" Since calculation of the uncatalyzed hydration of CO2 or dehydration of HCO3-in tissues involves some uncertainty, these rates are generally best defined by studying the dose-response curves of inhibitors and observing the residual activity after full inhibition."( Use of inhibitors in physiological studies of carbonic anhydrase.
Maren, TH, 1977
)
0.26
"We conclude that PEG-L-asparaginase is generally well tolerated in patients with advanced solid tumors, and a dosage of 2,000 IU/m2 by intramuscular injection every 2 weeks results in significant depletion of serum L-asparagine."( A phase I and pharmacodynamic evaluation of polyethylene glycol-conjugated L-asparaginase in patients with advanced solid tumors.
Dorr, RT; Fanta, P; Hersh, EM; Salmon, SE; Taylor, CW, 2001
)
0.31
" Dose-response curves (Fechner's law plots and n exponents from Stevens's power law) further demonstrated that DSM had a lower flavor binding potential than CSM."( Effect of enzymatic protein deamidation on protein solubility and flavor binding properties of soymilk.
Cadwallader, KR; Lee, SY; Suppavorasatit, I, 2013
)
0.39
" Moreover, this l-asparaginase was found to potentiate a lectin's induction of leukemic K562 cell apoptosis, allowing lowering of the drug dosage and shortening of the incubation time."( Biochemical characterization of a novel L-Asparaginase with low glutaminase activity from Rhizomucor miehei and its application in food safety and leukemia treatment.
Huang, L; Jiang, Z; Liu, Y; Sun, Y; Yan, Q, 2014
)
0.64
" When dosed systemically in swine, 13d provided a 15-fold enhanced CSF-to-plasma ratio and a 9-fold enhanced brain-to-plasma ratio relative to 14, opening a possible clinical path for the treatment of HAND."( N-(Pivaloyloxy)alkoxy-carbonyl Prodrugs of the Glutamine Antagonist 6-Diazo-5-oxo-l-norleucine (DON) as a Potential Treatment for HIV Associated Neurocognitive Disorders.
Alt, J; Brandacher, G; Chao, W; Dash, RP; Furtmüller, G; Gadiano, AJ; Garrett, C; Hadas, E; Jančařík, A; Kelschenbach, J; Kim, BH; Majer, P; Nedelcovych, MT; Oh, B; Prchalová, E; Rais, R; Slusher, BS; Tenora, L; Volsky, DJ; Zimmermann, SC, 2017
)
0.46
" However, high dosage of chemotherapy is associated with drug resistance and side effects."( Inhibition of lncRNA NEAT1 sensitizes medulloblastoma cells to cisplatin through modulating the miR-23a-3p-glutaminase (GLS) axis.
Ge, J; Wang, B; Xu, J; Zhao, S, 2022
)
0.93
" Hits from the screening were confirmed by retesting in dose-response with mass spectrometry-based cellular and biochemical assays."( New Platform for Label-Free, Proximal Cellular Pharmacodynamic Assays: Identification of Glutaminase Inhibitors Using Infrared Matrix-Assisted Laser Desorption Electrospray Ionization Mass Spectrometry.
Bruckner, BG; Elsen, NL; Fontaine, DA; Gopalakrishnan, SM; Panchal, SC; Pu, F; Radosevich, AJ; Williams, JD, 2023
)
1.13
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (1)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Protein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)IC50 (µMol)0.04500.04502.67428.0000AID1469834
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (24)

Processvia Protein(s)Taxonomy
gene expressionProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
dopamine secretionProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
chromatin remodelingProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
proteolysisProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
phospholipase C-activating G protein-coupled receptor signaling pathwayProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
peptide cross-linkingProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
protein deaminationProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
negative regulation of endoplasmic reticulum calcium ion concentrationProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
regulation of apoptotic processProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
positive regulation of apoptotic processProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
apoptotic cell clearanceProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
positive regulation of GTPase activityProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
positive regulation of cell adhesionProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
positive regulation of neurogenesisProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
positive regulation of small GTPase mediated signal transductionProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
positive regulation of mitochondrial calcium ion concentrationProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
bone developmentProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
branching involved in salivary gland morphogenesisProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
salivary gland cavitationProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
cellular response to cocaineProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
cellular response to dopamineProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
positive regulation of sprouting angiogenesisProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
cellular response to serotoninProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
regulation of apoptotic cell clearanceProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (10)

Processvia Protein(s)Taxonomy
protein-glutamine gamma-glutamyltransferase activityProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
calcium ion bindingProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
protein bindingProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
GTP bindingProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
peptidase activityProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
protein-glutamine glutaminase activityProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
histone serotonyltransferase activityProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
histone dopaminyltransferase activityProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
peptide noradrenalinyltransferase activityProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
peptide histaminyltransferase activityProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (12)

Processvia Protein(s)Taxonomy
collagen-containing extracellular matrixProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
nucleusProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
mitochondrionProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
endoplasmic reticulumProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
cytosolProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
plasma membraneProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
focal adhesionProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
extracellular matrixProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
perinuclear region of cytoplasmProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
collagen-containing extracellular matrixProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
extracellular exosomeProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
chromatinProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
nucleosomeProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
mitochondrionProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (5)

Assay IDTitleYearJournalArticle
AID1469837Selectivity ratio of IC50 for human TG6 to IC50 for human TG22017Journal of medicinal chemistry, 01-26, Volume: 60, Issue:2
Recent Progress in the Development of Transglutaminase 2 (TGase2) Inhibitors.
AID1469834Inhibition of human TG2 using glycine methyl ester/Abz-APE as substrate after 5 mins2017Journal of medicinal chemistry, 01-26, Volume: 60, Issue:2
Recent Progress in the Development of Transglutaminase 2 (TGase2) Inhibitors.
AID1469836Selectivity ratio of IC50 for human TG3 to IC50 for human TG22017Journal of medicinal chemistry, 01-26, Volume: 60, Issue:2
Recent Progress in the Development of Transglutaminase 2 (TGase2) Inhibitors.
AID1469835Selectivity ratio of IC50 for human TG1 to IC50 for human TG22017Journal of medicinal chemistry, 01-26, Volume: 60, Issue:2
Recent Progress in the Development of Transglutaminase 2 (TGase2) Inhibitors.
AID1469838Selectivity ratio of IC50 for human F13a to IC50 for human TG22017Journal of medicinal chemistry, 01-26, Volume: 60, Issue:2
Recent Progress in the Development of Transglutaminase 2 (TGase2) Inhibitors.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (2,173)

TimeframeStudies, This Drug (%)All Drugs %
pre-1990841 (38.70)18.7374
1990's296 (13.62)18.2507
2000's266 (12.24)29.6817
2010's506 (23.29)24.3611
2020's264 (12.15)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 53.69

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be very strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index53.69 (24.57)
Research Supply Index7.75 (2.92)
Research Growth Index4.73 (4.65)
Search Engine Demand Index91.66 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (53.69)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials11 (0.48%)5.53%
Reviews145 (6.30%)6.00%
Case Studies2 (0.09%)4.05%
Observational2 (0.09%)0.25%
Other2,141 (93.05%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]