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 Source | ID |
|---|---|
| PubMed CID | 10369242 |
| SCHEMBL ID | 2875156 |
| MeSH ID | M000598956 |
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.
| Excerpt | Reference | Relevance |
|---|---|---|
| "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
| Excerpt | Reference | Relevance |
|---|---|---|
| " 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
| Excerpt | Reference | Relevance |
|---|---|---|
| "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
| Excerpt | Relevance | Reference |
|---|---|---|
| " 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
| Protein | Taxonomy | Measurement | Average | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| Monocarboxylate transporter 1 | Homo sapiens (human) | Kd | 0.0016 | 0.0016 | 0.0016 | 0.0016 | AID1167921 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
Biological Processes (16)
Molecular Functions (9)
| Process | via Protein(s) | Taxonomy |
|---|---|---|
| protein binding | Monocarboxylate transporter 1 | Homo sapiens (human) |
| monocarboxylic acid transmembrane transporter activity | Monocarboxylate transporter 1 | Homo sapiens (human) |
| lactate transmembrane transporter activity | Monocarboxylate transporter 1 | Homo sapiens (human) |
| mevalonate transmembrane transporter activity | Monocarboxylate transporter 1 | Homo sapiens (human) |
| succinate transmembrane transporter activity | Monocarboxylate transporter 1 | Homo sapiens (human) |
| lactate:proton symporter activity | Monocarboxylate transporter 1 | Homo sapiens (human) |
| identical protein binding | Monocarboxylate transporter 1 | Homo sapiens (human) |
| carboxylic acid transmembrane transporter activity | Monocarboxylate transporter 1 | Homo sapiens (human) |
| organic cyclic compound binding | Monocarboxylate transporter 1 | Homo sapiens (human) |
| [Information is prepared from geneontology information from the June-17-2024 release] | ||
Ceullar Components (11)
Bioassays (10)
| Assay ID | Title | Year | Journal | Article |
|---|---|---|---|---|
| AID1167921 | Binding affinity to MCT1 (unknown origin) | 2014 | Bioorganic & medicinal chemistry letters, Nov-01, Volume: 24, Issue:21 | An update on therapeutic opportunities offered by cancer glycolytic metabolism. |
| AID1654519 | Inhibition of MCT1 in human A673 cells assessed as reduction in BrPA-induced cytotoxicity at 10 nM by SRB assay | 2020 | Journal 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 |
| AID1654520 | Growth inhibition of human A673 cells assessed as reduction in cell viability up to 10 uM after 48 hrs by SRB assay | 2020 | Journal 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 |
| AID1723954 | Antiplasmodial 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 method | 2020 | Journal 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. |
| AID1296008 | Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening | 2020 | SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1 | Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening. |
| AID1347159 | Primary screen GU Rhodamine qHTS for Zika virus inhibitors: Unlinked NS2B-NS3 protease assay | 2020 | Proceedings 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. |
| AID1346986 | P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen | 2019 | Molecular pharmacology, 11, Volume: 96, Issue:5 | A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein. |
| AID1346987 | P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen | 2019 | Molecular pharmacology, 11, Volume: 96, Issue:5 | A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein. |
| AID1347160 | Primary screen NINDS Rhodamine qHTS for Zika virus inhibitors | 2020 | Proceedings 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. |
| AID1347411 | qHTS 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) Libary | 2020 | ACS 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)
| Timeframe | Studies, This Drug (%) | All Drugs % |
|---|---|---|
| pre-1990 | 0 (0.00) | 18.7374 |
| 1990's | 0 (0.00) | 18.2507 |
| 2000's | 0 (0.00) | 29.6817 |
| 2010's | 17 (41.46) | 24.3611 |
| 2020's | 24 (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.
| This Compound (34.07) All Compounds (24.57) |
Study Types
| Publication Type | This drug (%) | All Drugs (%) |
|---|---|---|
| Trials | 1 (2.44%) | 5.53% |
| Reviews | 3 (7.32%) | 6.00% |
| Case Studies | 1 (2.44%) | 4.05% |
| Observational | 0 (0.00%) | 0.25% |
| Other | 36 (87.80%) | 84.16% |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||