Page last updated: 2024-11-12

azd3965

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

Description

AZD3965: a monocarboxylate transporter-1 inhibitor with antineoplastic activity; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID10369242
SCHEMBL ID2875156
MeSH IDM000598956

Synonyms (34)

Synonym
cid 10369242
S7339
5-[[(4s)-4-hydroxy-4-methyl-2-isoxazolidinyl]carbonyl]-3-methyl-1-(1-methylethyl)-6-[[5-methyl-3-(trifluoromethyl)-1h-pyrazol-4-yl]methyl]-thieno[2,3-d]pyrimidine-2,4(1h,3h)-dione
SCHEMBL2875156
azd3965
1448671-31-5
HY-12750
AC-33040
4-(2-{[5-methyl-1-(2-naphthyl)-1h-pyrazol-3-yl]oxy}ethyl)morpholine hydrochloride
J-690346
azd-3965 ,
azd 3965
EX-A806
AKOS027323783
(s)-5-(4-hydroxy-4-methylisoxazolidine-2-carbonyl)-1-isopropyl-3-methyl-6-((3-methyl-5-(trifluoromethyl)-1h-pyrazol-4-yl)methyl)thieno[2,3-d]pyrimidine-2,4(1h,3h)-dione
(s)-5-(4-hydroxy-4-methylisoxazolidine-2-carbonyl)-1-isopropyl-3-methyl-6-((5-methyl-3-(trifluoromethyl)-1h-pyrazol-4-yl)methyl)thieno[2,3-d]pyrimidine-2,4(1h,3h)-dione
NCGC00415059-01
733809-45-5
unii-39om5y4k2f
39OM5Y4K2F ,
azd 3965 [who-dd]
5-(((4s)-4-hydroxy-4-methyl-2-isoxazolidinyl)carbonyl)-3-methyl-1-(1-methylethyl)-6-((5-methyl-3-(trifluoromethyl)-1h-pyrazol-4-yl)methyl)thieno(2,3-d)pyrimidine-2,4(1h,3h)-dione
BCP17734
5-[(4s)-4-hydroxy-4-methyl-1,2-oxazolidine-2-carbonyl]-3-methyl-6-{[5-methyl-3-(trifluoromethyl)-1h-pyrazol-4-yl]methyl}-1-(propan-2-yl)-1h,2h,3h,4h-thieno[2,3-d]pyrimidine-2,4-dione
AS-75322
BCP09948
5-[(4s)-4-hydroxy-4-methyl-1,2-oxazolidine-2-carbonyl]-1-isopropyl-3-methyl-6-{[3-methyl-5-(trifluoromethyl)-2h-pyrazol-4-yl]methyl}thieno[2,3-d]pyrimidine-2,4-dione
HMS3873L03
CCG-269813
5-[(4s)-4-hydroxy-4-methyl-1,2-oxazolidine-2-carbonyl]-3-methyl-6-[[5-methyl-3-(trifluoromethyl)-1h-pyrazol-4-yl]methyl]-1-propan-2-ylthieno[2,3-d]pyrimidine-2,4-dione
gtpl10605
nsc-787047
nsc787047
BA164976

Research Excerpts

Treatment

AZD3965 treatment led to a rapid accumulation of intracellular lactate in a panel of lymphoma cell lines with low monocarboxylate transporter 4 protein expression and potently inhibited their proliferation.

ExcerptReferenceRelevance
"AZD3965 treatment resulted in trough plasma and tumor concentrations of 29.1 ± 13.9 and 1670 ± 946 nM, respectively."( In Vitro and In Vivo Efficacy of AZD3965 and Alpha-Cyano-4-Hydroxycinnamic Acid in the Murine 4T1 Breast Tumor Model.
Guan, X; Morris, ME, 2020
)
1.56
"AZD3965 treatment led to a rapid accumulation of intracellular lactate in a panel of lymphoma cell lines with low monocarboxylate transporter 4 protein expression and potently inhibited their proliferation."( Inhibition of monocarboxyate transporter 1 by AZD3965 as a novel therapeutic approach for diffuse large B-cell lymphoma and Burkitt lymphoma.
Bacon, CM; Bell, N; Blair, H; Bomken, S; Critchlow, SE; Crossland, R; Keun, HC; Long, A; Miwa, S; Nakjang, S; Noble, RA; Phillips, N; Rand, V; Sikka, A; Televantou, D; Thomas, H; Wedge, SR, 2017
)
1.43

Pharmacokinetics

ExcerptReferenceRelevance
" This assay was successfully applied to pharmacokinetic and murine 4T1 breast tumor xenograft studies of AZD3965 in mice."( Development and validation of a liquid chromatography tandem mass spectrometry assay for AZD3965 in mouse plasma and tumor tissue: Application to pharmacokinetic and breast tumor xenograft studies.
Guan, X; Morris, ME; Ruszaj, D, 2018
)
0.92

Bioavailability

ExcerptReferenceRelevance
"AZD3965, a pyrole pyrimidine derivative, is a potent and orally bioavailable inhibitor of monocarboxylate transporter 1 (MCT1), currently in a Phase I clinical trial in UK for lymphomas and solid tumors."( Development and validation of a liquid chromatography tandem mass spectrometry assay for AZD3965 in mouse plasma and tumor tissue: Application to pharmacokinetic and breast tumor xenograft studies.
Guan, X; Morris, ME; Ruszaj, D, 2018
)
2.15
"The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit both brain penetration and oral bioavailability of many chemotherapy drugs."( A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
Ambudkar, SV; Brimacombe, KR; Chen, L; Gottesman, MM; Guha, R; Hall, MD; Klumpp-Thomas, C; Lee, OW; Lee, TD; Lusvarghi, S; Robey, RW; Shen, M; Tebase, BG, 2019
)
0.51

Dosage Studied

ExcerptRelevanceReference
" The effects of AZD3965 on visual acuity and electroretinography (ERG) were further investigated in pigmented (Long-Evans) rats, with dosing for up to 7 days."( Effects of a monocarboxylate transport 1 inhibitor, AZD3965, on retinal and visual function in the rat.
Allen, AE; Grant, C; Greenwood, K; Lucas, RJ; Martin, EA; Redfern, WS; Vince, P, 2020
)
1.15
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (1)

Activation Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Monocarboxylate transporter 1Homo sapiens (human)Kd0.00160.00160.00160.0016AID1167921
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (16)

Processvia Protein(s)Taxonomy
lipid metabolic processMonocarboxylate transporter 1Homo sapiens (human)
centrosome cycleMonocarboxylate transporter 1Homo sapiens (human)
monocarboxylic acid transportMonocarboxylate transporter 1Homo sapiens (human)
mevalonate transportMonocarboxylate transporter 1Homo sapiens (human)
response to foodMonocarboxylate transporter 1Homo sapiens (human)
plasma membrane lactate transportMonocarboxylate transporter 1Homo sapiens (human)
glucose homeostasisMonocarboxylate transporter 1Homo sapiens (human)
pyruvate catabolic processMonocarboxylate transporter 1Homo sapiens (human)
regulation of insulin secretionMonocarboxylate transporter 1Homo sapiens (human)
behavioral response to nutrientMonocarboxylate transporter 1Homo sapiens (human)
cellular response to organic cyclic compoundMonocarboxylate transporter 1Homo sapiens (human)
succinate transmembrane transportMonocarboxylate transporter 1Homo sapiens (human)
transport across blood-brain barrierMonocarboxylate transporter 1Homo sapiens (human)
pyruvate transmembrane transportMonocarboxylate transporter 1Homo sapiens (human)
proton transmembrane transportMonocarboxylate transporter 1Homo sapiens (human)
carboxylic acid transmembrane transportMonocarboxylate transporter 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (9)

Processvia Protein(s)Taxonomy
protein bindingMonocarboxylate transporter 1Homo sapiens (human)
monocarboxylic acid transmembrane transporter activityMonocarboxylate transporter 1Homo sapiens (human)
lactate transmembrane transporter activityMonocarboxylate transporter 1Homo sapiens (human)
mevalonate transmembrane transporter activityMonocarboxylate transporter 1Homo sapiens (human)
succinate transmembrane transporter activityMonocarboxylate transporter 1Homo sapiens (human)
lactate:proton symporter activityMonocarboxylate transporter 1Homo sapiens (human)
identical protein bindingMonocarboxylate transporter 1Homo sapiens (human)
carboxylic acid transmembrane transporter activityMonocarboxylate transporter 1Homo sapiens (human)
organic cyclic compound bindingMonocarboxylate transporter 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (11)

Processvia Protein(s)Taxonomy
centrosomeMonocarboxylate transporter 1Homo sapiens (human)
plasma membraneMonocarboxylate transporter 1Homo sapiens (human)
basal plasma membraneMonocarboxylate transporter 1Homo sapiens (human)
membraneMonocarboxylate transporter 1Homo sapiens (human)
basolateral plasma membraneMonocarboxylate transporter 1Homo sapiens (human)
apical plasma membraneMonocarboxylate transporter 1Homo sapiens (human)
lateral plasma membraneMonocarboxylate transporter 1Homo sapiens (human)
cell junctionMonocarboxylate transporter 1Homo sapiens (human)
intracellular membrane-bounded organelleMonocarboxylate transporter 1Homo sapiens (human)
synapseMonocarboxylate transporter 1Homo sapiens (human)
extracellular exosomeMonocarboxylate transporter 1Homo sapiens (human)
basolateral plasma membraneMonocarboxylate transporter 1Homo sapiens (human)
plasma membraneMonocarboxylate transporter 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (10)

Assay IDTitleYearJournalArticle
AID1167921Binding affinity to MCT1 (unknown origin)2014Bioorganic & medicinal chemistry letters, Nov-01, Volume: 24, Issue:21
An update on therapeutic opportunities offered by cancer glycolytic metabolism.
AID1654519Inhibition of MCT1 in human A673 cells assessed as reduction in BrPA-induced cytotoxicity at 10 nM by SRB assay2020Journal of natural products, 03-27, Volume: 83, Issue:3
Using the Cancer Dependency Map to Identify the Mechanism of Action of a Cytotoxic Alkenyl Derivative from the Fruit of
AID1654520Growth inhibition of human A673 cells assessed as reduction in cell viability up to 10 uM after 48 hrs by SRB assay2020Journal of natural products, 03-27, Volume: 83, Issue:3
Using the Cancer Dependency Map to Identify the Mechanism of Action of a Cytotoxic Alkenyl Derivative from the Fruit of
AID1723954Antiplasmodial activity against Plasmodium falciparum 3D7 assessed as reduction in parasitemia incubated for 48 hrs supplemented with fresh medium containing compound at 24 hrs by LSR II FACS method2020Journal of medicinal chemistry, 09-10, Volume: 63, Issue:17
Introduction of Scaffold Nitrogen Atoms Renders Inhibitors of the Malarial l-Lactate Transporter, PfFNT, Effective against the Gly107Ser Resistance Mutation.
AID1296008Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening2020SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1
Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening.
AID1347159Primary screen GU Rhodamine qHTS for Zika virus inhibitors: Unlinked NS2B-NS3 protease assay2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1346986P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1346987P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1347160Primary screen NINDS Rhodamine qHTS for Zika virus inhibitors2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1347411qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS Mechanism Interrogation Plate v5.0 (MIPE) Libary2020ACS chemical biology, 07-17, Volume: 15, Issue:7
High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (41)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's0 (0.00)29.6817
2010's17 (41.46)24.3611
2020's24 (58.54)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 34.07

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 moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index34.07 (24.57)
Research Supply Index3.76 (2.92)
Research Growth Index4.67 (4.65)
Search Engine Demand Index43.69 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (34.07)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials1 (2.44%)5.53%
Reviews3 (7.32%)6.00%
Case Studies1 (2.44%)4.05%
Observational0 (0.00%)0.25%
Other36 (87.80%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]