Page last updated: 2024-12-04

diazooxonorleucine

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

Description

Diazooxonorleucine: An amino acid that inhibits phosphate-activated glutaminase and interferes with glutamine metabolism. It is an antineoplastic antibiotic produced by an unidentified species of Streptomyces from Peruvian soil. (From Merck Index, 11th ed) [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

6-diazo-5-oxo-L-norleucine : A non-proteinogenic L-alpha-amino acid that is L-norleucine which is substituted at position 5 by an oxo group and at position 6 by a diazo group. It is as inhibitor of various glutamine-utilising enzymes. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID9087
CHEMBL ID97485
CHEMBL ID4303391
CHEBI ID138889
SCHEMBL ID15349015
SCHEMBL ID15349013
MeSH IDM0006241

Synonyms (53)

Synonym
diazooxonorleucine
CHEMBL97485
157-03-9
NSC7365 ,
NCIMECH_000302
kmx-010
l-norleucine, 6-diazo-5-oxo-
nsc-7365
6-diazo-5-oxo-l-norleucine
(2s)-2-amino-6-diazo-5-oxo-hexanoic acid
l-don
ai3-26441
nsc 7365
brn 1725815
norleucine, 6-diazo-5-oxo, l-
don (pharmaceutical)
NCGC00013078
6-diazo-5-oxo-l-norleucine, crystalline
NCI7365
NCISTRUC1_000220
NCISTRUC2_000175
NCGC00096202-01
CHEBI:138889
(s)-2-amino-6-diazo-5-oxocaproic acid
(2s)-2-amino-6-diazo-5-oxohexanoic acid
l-norleucine,6-diazo-5-oxo-
CCG-37571
CCG-35449
NCGC00013078-02
l-6-diazo-5-oxonorleucine
unii-03j0h273kz
03j0h273kz ,
4-04-00-03278 (beilstein handbook reference)
norleucine,6-diazo-5-oxo-
6-diazo-5-oxo-l-norleucine [mi]
SCHEMBL15349015
SCHEMBL15349013
mfcd00037218
AKOS030213039
(l)-don
J-009370
6-diazo-5-oxo-l-nor-leucine
HY-108357
CS-0028442
Q245487
CHEMBL4303391
EX-A1965
A936514
F82153
diazo-5-oxo-l-norleucine, 6-
DTXSID501028846
nsc823855
nsc-823855

Research Excerpts

Pharmacokinetics

ExcerptReferenceRelevance
" The total body clearance, plasma t1/2, and area under the plasma concentration curve (AUC) were calculated using a noncompartmental method."( Pharmacokinetic and phase I study of intravenous DON (6-diazo-5-oxo-L-norleucine) in children.
Feldman, S; Nelson, JA; Sullivan, MP; Van Nguyen, B, 1988
)
0.27
" Analysis of the plasma elimination of DON demonstrated dose-dependent pharmacokinetic behavior."( Phase I and pharmacokinetic studies of DON.
Creagan, ET; Eagan, RT; Kovach, JS; Moertel, CG; Powis, G; Rubin, J,
)
0.13

Dosage Studied

ExcerptRelevanceReference
" Thus, thorough preliminary selection of appropriate inhibitors, their dosage and treatment duration is needed for the recommendation of combined enzyme-inhibitor application in anti-tumour chemotherapy."( [Inactivation of microbial glutamin-(asparagin-)ase by azaserine and 6-diazo-5-oxo-L-norleucine].
Berezov, TT; Kabanova, EA; Lebedeva, ZI, 1985
)
0.27
" 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
" Evaluation of past studies suggests that the major impediments to successful clinical use included unacceptable gastrointestinal (GI) toxicities, inappropriate dosing schedules for a metabolic inhibitor, and lack of targeted patient selection."( We're Not "DON" Yet: Optimal Dosing and Prodrug Delivery of
Lemberg, KM; Rais, R; Slusher, BS; Vornov, JJ, 2018
)
0.48
" Moreover, the KD-R diet facilitated DON delivery to the brain and allowed a lower dosage to achieve therapeutic effect."( Therapeutic benefit of combining calorie-restricted ketogenic diet and glutamine targeting in late-stage experimental glioblastoma.
Arismendi-Morillo, G; Augur, ZM; Bronson, RT; Chinopoulos, C; Domin, MA; Greenwood, B; Hill, C; Kiebish, MA; Kondakci, G; Li, M; Mukherjee, P; Narain, NR; Seyfried, TN, 2019
)
0.51
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (16)

RoleDescription
bacterial metaboliteAny prokaryotic metabolite produced during a metabolic reaction in bacteria.
analgesicAn agent capable of relieving pain without the loss of consciousness or without producing anaesthesia. In addition, analgesic is a role played by a compound which is exhibited by a capability to cause a reduction of pain symptoms.
antibacterial agentA substance (or active part thereof) that kills or slows the growth of bacteria.
antiviral agentA substance that destroys or inhibits replication of viruses.
antineoplastic agentA substance that inhibits or prevents the proliferation of neoplasms.
EC 6.3.5.5 [carbamoyl-phosphate synthase (glutamine-hydrolysing)] inhibitorAn EC 6.3.5.* (carbon-nitrogen ligases with glutamine as amido-N-donor) inhibitor that interferes with the action of carbamoyl-phosphate synthase (glutamine-hydrolysing) (EC 6.3.5.5).
EC 6.3.4.2 [CTP synthase (glutamine hydrolyzing)] inhibitorAny EC 6.3.4.* (other carbon--nitrogen ligases) inhibitor that interferes with the action of CTP synthase (glutamine hydrolyzing) (EC 6.3.4.2).
EC 6.3.5.3 (phosphoribosylformylglycinamidine synthase) inhibitorAny EC 6.3.5.* (carbon-nitrogen ligases with glutamine as amido-N-donor) inhibitor that interferes with the action of phosphoribosylformylglycinamidine synthase (EC 6.3.5.3).
EC 6.3.5.2 [GMP synthase (glutamine-hydrolysing)] inhibitorAn EC 6.3.5.* (carbon-nitrogen ligases with glutamine as amido-N-donor) inhibitor that interferes with the action of GMP synthase (glutamine-hydrolysing) (EC 6.3.5.2).
antimetaboliteA substance which is structurally similar to a metabolite but which competes with it or replaces it, and so prevents or reduces its normal utilization.
glutamine antagonistAn antagonist that acts on glutamine receptors.
apoptosis inducerAny substance that induces the process of apoptosis (programmed cell death) in multi-celled organisms.
EC 2.4.2.14 (amidophosphoribosyltransferase) inhibitorAny EC 2.4.2.* (pentosyltransferase) inhibitor that interferes with the action of amidophosphoribosyltransferase (EC 2.4.2.14).
EC 3.5.1.2 (glutaminase) inhibitorAny EC 3.5.1.* (non-peptide linear amide C-N hydrolase) inhibitor that interferes with the activity of a glutaminase (EC 3.5.1.2) and thus the generation of glutamate from glutamine.
EC 6.3.5.1 [NAD(+) synthase (glutamine-hydrolysing)] inhibitorAny EC 6.3.5.* (carbon-nitrogen ligases with glutamine as amido-N-donor) inhibitor that interferes with the action of NAD(+) synthase (glutamine-hydrolysing) (EC 6.3.5.1).
EC 6.3.5.4 [asparagine synthase (glutamine-hydrolysing)] inhibitorAny EC 6.3.5.* (carbon-nitrogen ligases with glutamine as amido-N-donor) inhibitor that interferes with the action of asparagine synthase (glutamine-hydrolysing), EC 6.3.5.4.
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (4)

ClassDescription
non-proteinogenic L-alpha-amino acidAny L-alpha-amino acid which is not a member of the group of 23 proteinogenic amino acids.
diazo compoundCompounds containing a group =N2 attached to a single carbon atom. They are named by adding the prefix 'diazo-' to the name of the parent hydride or functional parent.
ketoneA compound in which a carbonyl group is bonded to two carbon atoms: R2C=O (neither R may be H).
amino acid zwitterionThe zwitterionic form of an amino acid having a negatively charged carboxyl group and a positively charged amino group.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Bioassays (72)

Assay IDTitleYearJournalArticle
AID553850Antifungal activity against Saccharomyces cerevisiae ADCDR2 expressing Candida albicans CDR2 efflux pump in YNPG medium containing 1 mg/ml 1-glutamate after 24 hrs by microdilution method2008Antimicrobial agents and chemotherapy, Nov, Volume: 52, Issue:11
Enhanced susceptibility to antifungal oligopeptides in yeast strains overexpressing ABC multidrug efflux pumps.
AID1319388AUC (0 to t) in pig-tail monkey plasma at 1.6 mg/kg, iv measured at 0.25 to 6 hrs post dose by LC-MS analysis2016Journal of medicinal chemistry, Sep-22, Volume: 59, Issue:18
Discovery of 6-Diazo-5-oxo-l-norleucine (DON) Prodrugs with Enhanced CSF Delivery in Monkeys: A Potential Treatment for Glioblastoma.
AID1458489Effect on EcoHIV viral DNA load in infected C57BL/6J mouse brain at 1 mg/kg, ip qd starting 1 day prior to EcoHIV infection and continuing every other day till day 30 measured after 30 days post infection by qPCR method2017Journal of medicinal chemistry, 08-24, Volume: 60, Issue:16
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.
AID1319358Antitumor activity against human U87 cells xenografted in RHFoxn1nu mouse assessed as tumor volume at 0.8 mg/kg, ip qd for 6 days measured on day 2 post dose (Rvb = 401 mm3)2016Journal of medicinal chemistry, Sep-22, Volume: 59, Issue:18
Discovery of 6-Diazo-5-oxo-l-norleucine (DON) Prodrugs with Enhanced CSF Delivery in Monkeys: A Potential Treatment for Glioblastoma.
AID1544018Antiproliferative activity against human P493B cells measured after 72 hrs by CellTiter 96 aqueous one solution cell proliferation assay
AID1319370Cmax in C57BL/6 mouse plasma at 0.8 mg/kg administered via oral gavage by LC-MS analysis2016Journal of medicinal chemistry, Sep-22, Volume: 59, Issue:18
Discovery of 6-Diazo-5-oxo-l-norleucine (DON) Prodrugs with Enhanced CSF Delivery in Monkeys: A Potential Treatment for Glioblastoma.
AID409954Inhibition of mouse brain MAOA2008Journal of medicinal chemistry, Nov-13, Volume: 51, Issue:21
Quantitative structure-activity relationship and complex network approach to monoamine oxidase A and B inhibitors.
AID553856Antifungal activity against fluconazole resistant Candida albicans isolate B4 overexpressing MDR1 in RPMI-1640 buffered medium after 24 hrs by microdilution method2008Antimicrobial agents and chemotherapy, Nov, Volume: 52, Issue:11
Enhanced susceptibility to antifungal oligopeptides in yeast strains overexpressing ABC multidrug efflux pumps.
AID553849Antifungal activity against Saccharomyces cerevisiae ADCDR1 expressing Candida albicans CDR1 efflux pump in YNPG medium containing 1 mg/ml 1-glutamate after 24 hrs by microdilution method2008Antimicrobial agents and chemotherapy, Nov, Volume: 52, Issue:11
Enhanced susceptibility to antifungal oligopeptides in yeast strains overexpressing ABC multidrug efflux pumps.
AID1319364Toxicity in RHFoxn1nu mouse xenografted with human U87 cells assessed as lethargy at 0.8 mg/kg, ip qd for 6 days2016Journal of medicinal chemistry, Sep-22, Volume: 59, Issue:18
Discovery of 6-Diazo-5-oxo-l-norleucine (DON) Prodrugs with Enhanced CSF Delivery in Monkeys: A Potential Treatment for Glioblastoma.
AID553854Antifungal activity against fluconazole resistant Candida albicans isolate Gu5 overexpressing CDR1 and CDR2 in RPMI-1640 buffered medium after 24 hrs by microdilution method2008Antimicrobial agents and chemotherapy, Nov, Volume: 52, Issue:11
Enhanced susceptibility to antifungal oligopeptides in yeast strains overexpressing ABC multidrug efflux pumps.
AID393857Anticancer activity against mouse EAC cells xenografted in Swiss albino mouse assessed as inhibition of ascitic cell count at 1 mg/kg2009European journal of medicinal chemistry, Jan, Volume: 44, Issue:1
Possible anticancer agents: QSAR analogs of glutamamide: synthesis and pharmacological activity of 1,5-N,N'-disubstituted-2-(substituted benzenesulphonyl) glutamamides.
AID1319363Toxicity in RHFoxn1nu mouse xenografted with human U87 cells assessed as ptosis at 0.8 mg/kg, ip qd for 6 days2016Journal of medicinal chemistry, Sep-22, Volume: 59, Issue:18
Discovery of 6-Diazo-5-oxo-l-norleucine (DON) Prodrugs with Enhanced CSF Delivery in Monkeys: A Potential Treatment for Glioblastoma.
AID1319382Ratio of drug level in C57BL/6 mouse brain to plasma at 0.8 mg/kg administered via oral gavage2016Journal of medicinal chemistry, Sep-22, Volume: 59, Issue:18
Discovery of 6-Diazo-5-oxo-l-norleucine (DON) Prodrugs with Enhanced CSF Delivery in Monkeys: A Potential Treatment for Glioblastoma.
AID553534Drug accumulation in Saccharomyces cerevisiae AD12345678 reenergized with glucose at pH 6.0 assessed as intracellular accumulation after 60 mins by fluorescamine staining2008Antimicrobial agents and chemotherapy, Nov, Volume: 52, Issue:11
Enhanced susceptibility to antifungal oligopeptides in yeast strains overexpressing ABC multidrug efflux pumps.
AID1319386Tmax in pig-tail monkey plasma at 1.6 mg/kg, iv by LC-MS analysis2016Journal of medicinal chemistry, Sep-22, Volume: 59, Issue:18
Discovery of 6-Diazo-5-oxo-l-norleucine (DON) Prodrugs with Enhanced CSF Delivery in Monkeys: A Potential Treatment for Glioblastoma.
AID1458474Total plasma concentration in swine at 1.6 mg/kg, iv infusion via saphenous vein after 60 mins by LC-MS/MS analysis2017Journal of medicinal chemistry, 08-24, Volume: 60, Issue:16
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.
AID1319390Drug uptake in pig-tail monkey CSF at 1.6 mg/kg, iv measured at 30 mins post dose by LC-MS analysis2016Journal of medicinal chemistry, Sep-22, Volume: 59, Issue:18
Discovery of 6-Diazo-5-oxo-l-norleucine (DON) Prodrugs with Enhanced CSF Delivery in Monkeys: A Potential Treatment for Glioblastoma.
AID1319371Cmax in C57BL/6 mouse brain at 0.8 mg/kg administered via oral gavage by LC-MS analysis2016Journal of medicinal chemistry, Sep-22, Volume: 59, Issue:18
Discovery of 6-Diazo-5-oxo-l-norleucine (DON) Prodrugs with Enhanced CSF Delivery in Monkeys: A Potential Treatment for Glioblastoma.
AID1458486Decrease in cognitive decline in C57BL/6J mouse EcoHIV associated neurocognitive disorder model assessed as decrease in number of errors across learning trial 1 to 4 and retention trial at 1 mg/kg, ip qd starting 1 day prior to EcoHIV infection and contin2017Journal of medicinal chemistry, 08-24, Volume: 60, Issue:16
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.
AID553847Antifungal activity against wild type Saccharomyces cerevisiae ATCC 9763 in YNPG medium containing 1 mg/ml 1-glutamate after 24 hrs by microdilution method2008Antimicrobial agents and chemotherapy, Nov, Volume: 52, Issue:11
Enhanced susceptibility to antifungal oligopeptides in yeast strains overexpressing ABC multidrug efflux pumps.
AID553522Drug uptake in Saccharomyces cerevisiae ADMDR1 expressing Candida albicans MDR1 efflux pump at 200 uM pretreated for 10 mins measured after 60 mins by fluorescamine staining2008Antimicrobial agents and chemotherapy, Nov, Volume: 52, Issue:11
Enhanced susceptibility to antifungal oligopeptides in yeast strains overexpressing ABC multidrug efflux pumps.
AID553520Drug uptake in Saccharomyces cerevisiae ADCDR2 expressing Candida albicans CDR2 efflux pump at 200 uM pretreated for 10 mins measured after 60 mins by fluorescamine staining2008Antimicrobial agents and chemotherapy, Nov, Volume: 52, Issue:11
Enhanced susceptibility to antifungal oligopeptides in yeast strains overexpressing ABC multidrug efflux pumps.
AID1319379AUC (0 to t) in C57BL/6 mouse brain at 0.8 mg/kg administered via oral gavage measured at 10 to 90 mins post dose by LC-MS analysis2016Journal of medicinal chemistry, Sep-22, Volume: 59, Issue:18
Discovery of 6-Diazo-5-oxo-l-norleucine (DON) Prodrugs with Enhanced CSF Delivery in Monkeys: A Potential Treatment for Glioblastoma.
AID553518Drug uptake in Saccharomyces cerevisiae ADCDR1 expressing Candida albicans CDR1 efflux pump at 200 uM pretreated for 10 mins measured after 60 mins by fluorescamine staining2008Antimicrobial agents and chemotherapy, Nov, Volume: 52, Issue:11
Enhanced susceptibility to antifungal oligopeptides in yeast strains overexpressing ABC multidrug efflux pumps.
AID1319375Tmax in C57BL/6 mouse brain at 0.8 mg/kg administered via oral gavage by LC-MS analysis2016Journal of medicinal chemistry, Sep-22, Volume: 59, Issue:18
Discovery of 6-Diazo-5-oxo-l-norleucine (DON) Prodrugs with Enhanced CSF Delivery in Monkeys: A Potential Treatment for Glioblastoma.
AID553535Drug accumulation in Saccharomyces cerevisiae ADCDR1 expressing Candida albicans CDR1 efflux pump reenergized with glucose at pH 6.0 assessed as intracellular accumulation after 60 mins by fluorescamine staining2008Antimicrobial agents and chemotherapy, Nov, Volume: 52, Issue:11
Enhanced susceptibility to antifungal oligopeptides in yeast strains overexpressing ABC multidrug efflux pumps.
AID1458463Toxicity in EcoHIV-infected C57BL/6J mouse assessed as change in motor function at 1 mg/kg, ip qd starting 1 day prior to EcoHIV infection and continuing every other day till day 30 measured after 30 days post infection2017Journal of medicinal chemistry, 08-24, Volume: 60, Issue:16
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.
AID1458485Decrease in cognitive decline in C57BL/6J mouse EcoHIV associated neurocognitive disorder model assessed as decrease in latency to escape to hidden platform at 1 mg/kg, ip qd starting 1 day prior to EcoHIV infection and continuing every other day till day2017Journal of medicinal chemistry, 08-24, Volume: 60, Issue:16
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.
AID553848Antifungal activity against Saccharomyces cerevisiae AD12345678 in YNPG medium containing 1 mg/ml 1-glutamate after 24 hrs by microdilution method2008Antimicrobial agents and chemotherapy, Nov, Volume: 52, Issue:11
Enhanced susceptibility to antifungal oligopeptides in yeast strains overexpressing ABC multidrug efflux pumps.
AID1458473Total drug uptake in swine brain at 1.6 mg/kg, iv infusion via saphenous vein after 60 mins by LC-MS/MS analysis2017Journal of medicinal chemistry, 08-24, Volume: 60, Issue:16
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.
AID1458472AUC (0 to t) in swine at 1.6 mg/kg, iv infusion via saphenous vein after 5 to 60 mins by LC-MS/MS analysis2017Journal of medicinal chemistry, 08-24, Volume: 60, Issue:16
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.
AID1458487Effect on latency to escape to visible platform in C57BL/6J mouse EcoHIV associated neurocognitive disorder model at 1 mg/kg, ip qd starting 1 day prior to EcoHIV infection and continuing every other day till day 30 measured after 30 days post infection b2017Journal of medicinal chemistry, 08-24, Volume: 60, Issue:16
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.
AID74394Steady-state inactivation rate constant for inactivation of Escherichia coli glucosamine synthetase was determined2000Bioorganic & medicinal chemistry letters, Dec-18, Volume: 10, Issue:24
Inhibition of Escherichia coli glucosamine synthetase by novel electrophilic analogues of glutamine--comparison with 6-diazo-5-oxo-norleucine.
AID1458461Unbound drug level in swine brain at 1.6 mg/kg, iv infusion via saphenous vein after 60 mins by LC-MS/MS analysis2017Journal of medicinal chemistry, 08-24, Volume: 60, Issue:16
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.
AID1319357Antitumor activity against human U87 cells xenografted in RHFoxn1nu mouse assessed as tumor volume at 0.8 mg/kg, ip qd for 6 days measured immediately post dose (Rvb = 409 mm3)2016Journal of medicinal chemistry, Sep-22, Volume: 59, Issue:18
Discovery of 6-Diazo-5-oxo-l-norleucine (DON) Prodrugs with Enhanced CSF Delivery in Monkeys: A Potential Treatment for Glioblastoma.
AID1319359Antitumor activity against human U87 cells xenografted in RHFoxn1nu mouse assessed as tumor volume at 0.8 mg/kg, ip qd for 6 days measured on day 4 post dose (Rvb = 454 mm3)2016Journal of medicinal chemistry, Sep-22, Volume: 59, Issue:18
Discovery of 6-Diazo-5-oxo-l-norleucine (DON) Prodrugs with Enhanced CSF Delivery in Monkeys: A Potential Treatment for Glioblastoma.
AID1458476Total drug uptake in swine cerebrospinal fluid at 1.6 mg/kg, iv infusion via saphenous vein after 60 mins by LC-MS/MS analysis2017Journal of medicinal chemistry, 08-24, Volume: 60, Issue:16
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.
AID1458477Ratio of total drug level in swine brain to plasma at 1.6 mg/kg, iv infusion via saphenous vein after 60 mins by LC-MS/MS analysis2017Journal of medicinal chemistry, 08-24, Volume: 60, Issue:16
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.
AID1458478Ratio of total drug level in swine cerebrospinal fluid to plasma at 1.6 mg/kg, iv infusion via saphenous vein after 60 mins by LC-MS/MS analysis2017Journal of medicinal chemistry, 08-24, Volume: 60, Issue:16
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.
AID1458465Toxicity in EcoHIV-infected C57BL/6J mouse assessed as diarrhea at 1 mg/kg, ip qd starting 1 day prior to EcoHIV infection and continuing every other day till day 30 measured after 30 days post infection2017Journal of medicinal chemistry, 08-24, Volume: 60, Issue:16
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.
AID1458481Ratio of total drug level in swine cerebrospinal fluid to unbound plasma concentration in swine at 1.6 mg/kg, iv infusion via saphenous vein after 60 mins by LC-MS/MS analysis2017Journal of medicinal chemistry, 08-24, Volume: 60, Issue:16
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.
AID478476Antitumor activity against ip dosed mouse EAC implanted in Swiss albino mouse assessed as inhibition of ascitic fluid administered daily for 7 days measured on 9th day relative to control2010European journal of medicinal chemistry, May, Volume: 45, Issue:5
Synthesis, pharmacological activity and comparative QSAR modeling of 1,5-N,N'-substituted-2-(substituted naphthalenesulphonyl) glutamamides as possible anticancer agents.
AID1319378AUC (0 to t) in C57BL/6 mouse plasma at 0.8 mg/kg administered via oral gavage measured at 10 to 90 mins post dose by LC-MS analysis2016Journal of medicinal chemistry, Sep-22, Volume: 59, Issue:18
Discovery of 6-Diazo-5-oxo-l-norleucine (DON) Prodrugs with Enhanced CSF Delivery in Monkeys: A Potential Treatment for Glioblastoma.
AID1458482Protein binding in swine brain at 10 uM after 30 mins by ultrafiltration method2017Journal of medicinal chemistry, 08-24, Volume: 60, Issue:16
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.
AID553853Antifungal activity against fluconazole sensitive Candida albicans isolate Gu4 in RPMI-1640 buffered medium after 24 hrs by microdilution method2008Antimicrobial agents and chemotherapy, Nov, Volume: 52, Issue:11
Enhanced susceptibility to antifungal oligopeptides in yeast strains overexpressing ABC multidrug efflux pumps.
AID1544004Drug level in human P493B cells suspended in human plasma assessed as tumor cell to plasma ratio at 20 uM measured after 1 hr by LC-MS/MS analysis
AID1458475Unbound plasma concentration in swine at 1.6 mg/kg, iv infusion via saphenous vein after 60 mins by LC-MS/MS analysis2017Journal of medicinal chemistry, 08-24, Volume: 60, Issue:16
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.
AID1319374Tmax in C57BL/6 mouse plasma at 0.8 mg/kg administered via oral gavage by LC-MS analysis2016Journal of medicinal chemistry, Sep-22, Volume: 59, Issue:18
Discovery of 6-Diazo-5-oxo-l-norleucine (DON) Prodrugs with Enhanced CSF Delivery in Monkeys: A Potential Treatment for Glioblastoma.
AID553851Antifungal activity against Saccharomyces cerevisiae ADMDR1 expressing Candida albicans MDR1 efflux pump in YNPG medium containing 1 mg/ml 1-glutamate after 24 hrs by microdilution method2008Antimicrobial agents and chemotherapy, Nov, Volume: 52, Issue:11
Enhanced susceptibility to antifungal oligopeptides in yeast strains overexpressing ABC multidrug efflux pumps.
AID1458483Fraction unbound in swine brain at 1.6 mg/kg, iv infusion via saphenous vein after 60 min post-infusion by LC-MS/MS analysis2017Journal of medicinal chemistry, 08-24, Volume: 60, Issue:16
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.
AID393856Anticancer activity against mouse EAC cells xenografted in Swiss albino mouse assessed as inhibition of ascitic fluid weight at 1 mg/kg2009European journal of medicinal chemistry, Jan, Volume: 44, Issue:1
Possible anticancer agents: QSAR analogs of glutamamide: synthesis and pharmacological activity of 1,5-N,N'-disubstituted-2-(substituted benzenesulphonyl) glutamamides.
AID553852Antifungal activity against wild type Candida albicans 10261 in RPMI-1640 buffered medium after 24 hrs by microdilution method2008Antimicrobial agents and chemotherapy, Nov, Volume: 52, Issue:11
Enhanced susceptibility to antifungal oligopeptides in yeast strains overexpressing ABC multidrug efflux pumps.
AID553536Drug accumulation in Saccharomyces cerevisiae ADCDR2 expressing Candida albicans CDR2 efflux pump reenergized with glucose at pH 6.0 after 60 mins by fluorescamine staining2008Antimicrobial agents and chemotherapy, Nov, Volume: 52, Issue:11
Enhanced susceptibility to antifungal oligopeptides in yeast strains overexpressing ABC multidrug efflux pumps.
AID74392Limiting rate constant for inactivation of Escherichia coli glucosamine synthetase was determined2000Bioorganic & medicinal chemistry letters, Dec-18, Volume: 10, Issue:24
Inhibition of Escherichia coli glucosamine synthetase by novel electrophilic analogues of glutamine--comparison with 6-diazo-5-oxo-norleucine.
AID1458464Toxicity in EcoHIV-infected C57BL/6J mouse assessed as change in body weight at 1 mg/kg, ip qd starting 1 day prior to EcoHIV infection and continuing every other day till day 30 measured after 30 days post infection2017Journal of medicinal chemistry, 08-24, Volume: 60, Issue:16
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.
AID1458462Toxicity in EcoHIV-infected C57BL/6J mouse assessed as change in visual impairment at 1 mg/kg, ip qd starting 1 day prior to EcoHIV infection and continuing every other day till day 30 measured after 30 days post infection2017Journal of medicinal chemistry, 08-24, Volume: 60, Issue:16
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.
AID1458484Protein binding in swine plasma at 10 uM after 30 mins by ultrafiltration method2017Journal of medicinal chemistry, 08-24, Volume: 60, Issue:16
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.
AID1319356Invivo inhibition of glutamine metabolism in RHFoxn1nu mouse xenografted with human U87 cells assessed as accumulation of endogenous glutamine in tumor at 0.8 mg/kg, ip administered as single dose measured after 2 hrs by HPLC-MS analysis2016Journal of medicinal chemistry, Sep-22, Volume: 59, Issue:18
Discovery of 6-Diazo-5-oxo-l-norleucine (DON) Prodrugs with Enhanced CSF Delivery in Monkeys: A Potential Treatment for Glioblastoma.
AID1319384Cmax in pig-tail monkey plasma at 1.6 mg/kg, iv by LC-MS analysis2016Journal of medicinal chemistry, Sep-22, Volume: 59, Issue:18
Discovery of 6-Diazo-5-oxo-l-norleucine (DON) Prodrugs with Enhanced CSF Delivery in Monkeys: A Potential Treatment for Glioblastoma.
AID553516Drug uptake in Saccharomyces cerevisiae AD12345678 at 200 uM pretreated for 10 mins measured after 60 mins by fluorescamine staining2008Antimicrobial agents and chemotherapy, Nov, Volume: 52, Issue:11
Enhanced susceptibility to antifungal oligopeptides in yeast strains overexpressing ABC multidrug efflux pumps.
AID1458488Increase in EcoHIV viral DNA load in infected C57BL/6J mouse spleen at 1 mg/kg, ip qd starting 1 day prior to EcoHIV infection and continuing every other day till day 30 measured after 30 days post infection by qPCR method2017Journal of medicinal chemistry, 08-24, Volume: 60, Issue:16
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.
AID553855Antifungal activity against fluconazole sensitive Candida albicans isolate B3 in RPMI-1640 buffered medium after 24 hrs by microdilution method2008Antimicrobial agents and chemotherapy, Nov, Volume: 52, Issue:11
Enhanced susceptibility to antifungal oligopeptides in yeast strains overexpressing ABC multidrug efflux pumps.
AID1458479Ratio of total drug level in swine cerebrospinal fluid to unbound drug level in swine brain at 1.6 mg/kg, iv infusion via saphenous vein after 60 mins by LC-MS/MS analysis2017Journal of medicinal chemistry, 08-24, Volume: 60, Issue:16
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.
AID227760Second order rate constant (Ki / K+2) with Escherichia coli glucosamine synthetase2000Bioorganic & medicinal chemistry letters, Dec-18, Volume: 10, Issue:24
Inhibition of Escherichia coli glucosamine synthetase by novel electrophilic analogues of glutamine--comparison with 6-diazo-5-oxo-norleucine.
AID1319360Antitumor activity against human U87 cells xenografted in RHFoxn1nu mouse assessed as tumor volume at 0.8 mg/kg, ip qd for 6 days measured on day 6 post dose (Rvb = 533 mm3)2016Journal of medicinal chemistry, Sep-22, Volume: 59, Issue:18
Discovery of 6-Diazo-5-oxo-l-norleucine (DON) Prodrugs with Enhanced CSF Delivery in Monkeys: A Potential Treatment for Glioblastoma.
AID1458480Ratio of unbound drug level in swine brain to plasma at 1.6 mg/kg, iv infusion via saphenous vein after 60 mins by LC-MS/MS analysis2017Journal of medicinal chemistry, 08-24, Volume: 60, Issue:16
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.
AID1319362Toxicity in RHFoxn1nu mouse xenografted with human U87 cells assessed as hunching at 0.8 mg/kg, ip qd for 6 days2016Journal of medicinal chemistry, Sep-22, Volume: 59, Issue:18
Discovery of 6-Diazo-5-oxo-l-norleucine (DON) Prodrugs with Enhanced CSF Delivery in Monkeys: A Potential Treatment for Glioblastoma.
AID1319369Antitumor activity against human U87 cells xenografted in RHFoxn1nu mouse assessed as reduction in tumor volume at 0.8 mg/kg, ip qd for 6 days measured 2 to 6 days post dose2016Journal of medicinal chemistry, Sep-22, Volume: 59, Issue:18
Discovery of 6-Diazo-5-oxo-l-norleucine (DON) Prodrugs with Enhanced CSF Delivery in Monkeys: A Potential Treatment for Glioblastoma.
AID478477Antitumor activity against ip dosed mouse EAC implanted in Swiss albino mouse assessed as inhibition of ascitic cell administered daily for 7 days measured on 9th day relative to control2010European journal of medicinal chemistry, May, Volume: 45, Issue:5
Synthesis, pharmacological activity and comparative QSAR modeling of 1,5-N,N'-substituted-2-(substituted naphthalenesulphonyl) glutamamides as possible anticancer agents.
AID1319361Toxicity in RHFoxn1nu mouse xenografted with human U87 cells assessed as weight loss at 0.8 mg/kg, ip qd for 6 days2016Journal of medicinal chemistry, Sep-22, Volume: 59, Issue:18
Discovery of 6-Diazo-5-oxo-l-norleucine (DON) Prodrugs with Enhanced CSF Delivery in Monkeys: A Potential Treatment for Glioblastoma.
AID409956Inhibition of mouse brain MAOB2008Journal of medicinal chemistry, Nov-13, Volume: 51, Issue:21
Quantitative structure-activity relationship and complex network approach to monoamine oxidase A and B inhibitors.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (325)

TimeframeStudies, This Drug (%)All Drugs %
pre-1990168 (51.69)18.7374
1990's52 (16.00)18.2507
2000's35 (10.77)29.6817
2010's46 (14.15)24.3611
2020's24 (7.38)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials1 (0.30%)5.53%
Reviews14 (4.18%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other320 (95.52%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (1)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
DON in Pediatric Cerebral Malaria: A Phase I/IIa Dose-Escalation Safety Study [NCT05478720]Phase 1/Phase 2152 participants (Anticipated)Interventional2022-08-16Recruiting
[information is prepared from clinicaltrials.gov, extracted Sep-2024]