Page last updated: 2024-10-14
azd1981
Cross-References
| ID Source | ID |
|---|---|
| PubMed CID | 11292191 |
| CHEMBL ID | 1914489 |
| SCHEMBL ID | 1053662 |
| MeSH ID | M0570228 |
Synonyms (44)
| Synonym |
|---|
| azd-1981 |
| azd1981 , |
| azd 1981 |
| CHEMBL1914489 , |
| bdbm50357102 |
| azd 1981 [who-dd] |
| S7263 , |
| JWYIGNODXSRKGP-UHFFFAOYSA-N , |
| [4-acetylamino-3-(4-chlorophenylsulfanyl)-2-methyl-1h-indol-1-yl]acetic acid |
| 2-[4-acetamido-3-(4-chlorophenyl)sulfanyl-2-methylindol-1-yl]acetic acid |
| gtpl7680 |
| unii-2ad53wq2cx |
| 802904-66-1 |
| 2ad53wq2cx , |
| 1h-indole-1-acetic acid, 4-(acetylamino)-3-((4-chlorophenyl)thio)-2-methyl- |
| SCHEMBL1053662 |
| CS-4189 |
| 2-(4-acetamido-3-(4-chlorophenylthio)-2-methyl-1h-indol-1-yl)acetic acid |
| AC-33101 |
| HY-15950 |
| AC-33100 |
| 2-(4-acetamido-3-((4-chlorophenyl)thio)-2-methyl-1h-indol-1-yl)acetic acid |
| n-[(1s)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methylthieno[3,2-d]pyrimidin-4-yl)amino]-4,6-dihydropyrrolo[3,4-c]pyrazo le-5(1h)-carboxamide |
| J-690352 |
| EX-A662 |
| AKOS027263775 |
| 2-{3-[(4-chlorophenyl)sulfanyl]-4-acetamido-2-methyl-1h-indol-1-yl}acetic acid |
| HMS3653A06 |
| mfcd26936340 |
| NCGC00386290-04 |
| SW219735-1 |
| DB11946 |
| FT-0700366 |
| BCP20957 |
| AS-75220 |
| Q27074719 |
| 7-methyl-5-[(3-piperazin-1-ylmethyl)-1,2,4-oxadiazol-5-yl-]-2-[4-(trifluoromethoxy)benzyl]-2,3-dihydro-1h-isoindol-1-one methanesulphonate |
| SB16902 |
| CCG-268510 |
| 4-(acetylamino)-3-[(4-chlorophenyl)thio]-2-methyl-1h-indole-1-acetic acid |
| A864713 |
| CHB90466 |
| DTXSID901025620 |
| 4-(acetylamino)-3-((4-chlorophenyl)thio)-2-methyl-1h-indole-1-acetic acid |
Research Excerpts
Overview
AZD1981 is a selective antagonist of chemoattractant receptor-homologous molecule expressed on T helper type 2 and other type 2 cells, including innate lymphoid cells type 2, eosinophils, and basophils. AZD 1981 has progressed to phase II trials for the treatment of allergic asthma.
Treatment
AZD1981 treatment was well tolerated, effectively inhibited PGD2-mediated eosinophil shape change, shifted numbers of circulating eos inophils, and reduced weekly itch scores more than hives.
| Excerpt | Reference |
|---|---|
| "AZD1981 treatment increased circulating eosinophils and significantly impaired PGD2-mediated eosinophil shape change." | ( Effects of an Oral CRTh2 Antagonist (AZD1981) on Eosinophil Activity and Symptoms in Chronic Spontaneous Urticaria. Chichester, K; Devine, K; Oliver, ET; Saini, SS; Sterba, PM; Vonakis, BM; Wegner, C, 2019) |
| "AZD1981 treatment was well tolerated, effectively inhibited PGD2-mediated eosinophil shape change, shifted numbers of circulating eosinophils, and reduced weekly itch scores more than hives during treatment and into washout." | ( Effects of an Oral CRTh2 Antagonist (AZD1981) on Eosinophil Activity and Symptoms in Chronic Spontaneous Urticaria. Chichester, K; Devine, K; Oliver, ET; Saini, SS; Sterba, PM; Vonakis, BM; Wegner, C, 2019) |
Bioavailability
| Excerpt | Reference |
|---|---|
| "AZD1981 is an orally bioavailable chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTh2) receptor antagonist progressed to phase II trials for the treatment of allergic asthma." | ( An S-warfarin and AZD1981 interaction: in vitro and clinical pilot data suggest the N-deacetylated amino acid metabolite as the primary perpetrator. Brännström, M; Brealey, C; Gillen, M; Grime, K; Jones, B; Kühn, W; Mant, T; Nordell, P; Pehrson, R; Svanberg, P, 2017) |
| "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) |
Dosage Studied
| Excerpt | Reference |
|---|---|
| "022); however, there was no dose-response relationship." | ( Two Phase II randomized trials on the CRTh2 antagonist AZD1981 in adults with asthma. Bjermer, L; Kuna, P; Tornling, G, 2016) |
| " In this paper, four methods that assume a number of pre-defined model structure candidates, for example a set of dose-response shape functions, and then combine or select those candidate models are introduced." | ( Model selection and averaging of nonlinear mixed-effect models for robust phase III dose selection. Aoki, Y; Hamrén, B; Hooker, AC; Röshammar, D, 2017) |
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]
Protein Targets (12)
Potency Measurements
| Protein | Taxonomy | Measurement | Average (µ) | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| cytochrome P450 family 3 subfamily A polypeptide 4 | Homo sapiens (human) | Potency | 37.9083 | 0.0123 | 7.9835 | 43.2770 | AID1645841 |
| G | Vesicular stomatitis virus | Potency | 13.4504 | 0.0123 | 8.9648 | 39.8107 | AID1645842 |
| Interferon beta | Homo sapiens (human) | Potency | 13.4504 | 0.0033 | 9.1582 | 39.8107 | AID1645842 |
| HLA class I histocompatibility antigen, B alpha chain | Homo sapiens (human) | Potency | 13.4504 | 0.0123 | 8.9648 | 39.8107 | AID1645842 |
| Inositol hexakisphosphate kinase 1 | Homo sapiens (human) | Potency | 13.4504 | 0.0123 | 8.9648 | 39.8107 | AID1645842 |
| cytochrome P450 2C9, partial | Homo sapiens (human) | Potency | 13.4504 | 0.0123 | 8.9648 | 39.8107 | AID1645842 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
Inhibition Measurements
| Protein | Taxonomy | Measurement | Average | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| Cytochrome P450 1A2 | Homo sapiens (human) | IC50 (µMol) | 10.0000 | 0.0001 | 1.7740 | 10.0000 | AID630022 |
| Cytochrome P450 3A4 | Homo sapiens (human) | IC50 (µMol) | 10.0000 | 0.0001 | 1.7536 | 10.0000 | AID630024 |
| Cytochrome P450 2D6 | Homo sapiens (human) | IC50 (µMol) | 10.0000 | 0.0000 | 2.0151 | 10.0000 | AID630023 |
| Cytochrome P450 2C9 | Homo sapiens (human) | IC50 (µMol) | 10.0000 | 0.0000 | 2.8005 | 10.0000 | AID630021 |
| Aldo-keto reductase family 1 member B1 | Homo sapiens (human) | IC50 (µMol) | 0.7940 | 0.0010 | 1.1913 | 10.0000 | AID630018 |
| Prostaglandin D2 receptor 2 | Homo sapiens (human) | IC50 (µMol) | 0.0062 | 0.0004 | 0.1009 | 0.9600 | AID630011; AID630034; AID705353 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
Biological Processes (107)
Molecular Functions (63)
Ceullar Components (26)
Bioassays (25)
| Assay ID | Title | Year | Journal | Article |
|---|---|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| AID630024 | Inhibition of CYP3A4 | 2011 | Bioorganic & medicinal chemistry letters, Nov-01, Volume: 21, Issue:21 | Substituted indole-1-acetic acids as potent and selective CRTh2 antagonists-discovery of AZD1981. |
| AID630011 | Displacement of [3H]PGD2 from human CRTH2 receptor | 2011 | Bioorganic & medicinal chemistry letters, Nov-01, Volume: 21, Issue:21 | Substituted indole-1-acetic acids as potent and selective CRTh2 antagonists-discovery of AZD1981. |
| AID630034 | Antagonist activity against human CRTh2 receptor in human eosinophils assessed as inhibition of DK-PGD2-induced CD11b expression | 2011 | Bioorganic & medicinal chemistry letters, Nov-01, Volume: 21, Issue:21 | Substituted indole-1-acetic acids as potent and selective CRTh2 antagonists-discovery of AZD1981. |
| AID630019 | Intrinsic clearance in rat hepatocytes assessed as per 1 x 10'6 cells | 2011 | Bioorganic & medicinal chemistry letters, Nov-01, Volume: 21, Issue:21 | Substituted indole-1-acetic acids as potent and selective CRTh2 antagonists-discovery of AZD1981. |
| AID630027 | Clearance in Sprague-Dawley rat at 1 mg/kg, iv | 2011 | Bioorganic & medicinal chemistry letters, Nov-01, Volume: 21, Issue:21 | Substituted indole-1-acetic acids as potent and selective CRTh2 antagonists-discovery of AZD1981. |
| AID630018 | Inhibition of human recombinant aldose reductase 1 after 15 mins by spectrophotometry analysis | 2011 | Bioorganic & medicinal chemistry letters, Nov-01, Volume: 21, Issue:21 | Substituted indole-1-acetic acids as potent and selective CRTh2 antagonists-discovery of AZD1981. |
| AID630030 | Oral bioavailability in Sprague-Dawley rat at 4 mg/kg | 2011 | Bioorganic & medicinal chemistry letters, Nov-01, Volume: 21, Issue:21 | Substituted indole-1-acetic acids as potent and selective CRTh2 antagonists-discovery of AZD1981. |
| AID630017 | Inhibition of human recombinant aldose reductase 2 after 15 mins by spectrophotometry analysis | 2011 | Bioorganic & medicinal chemistry letters, Nov-01, Volume: 21, Issue:21 | Substituted indole-1-acetic acids as potent and selective CRTh2 antagonists-discovery of AZD1981. |
| AID630020 | Intrinsic clearance in human liver microsomes assessed as per mg of tissue | 2011 | Bioorganic & medicinal chemistry letters, Nov-01, Volume: 21, Issue:21 | Substituted indole-1-acetic acids as potent and selective CRTh2 antagonists-discovery of AZD1981. |
| AID630026 | Antagonist activity at prostanoid TP receptor assessed as inhibition of arachidonic acid-induced platelet aggregation at >/= 1 uM | 2011 | Bioorganic & medicinal chemistry letters, Nov-01, Volume: 21, Issue:21 | Substituted indole-1-acetic acids as potent and selective CRTh2 antagonists-discovery of AZD1981. |
| AID630022 | Inhibition of CYP1A2 | 2011 | Bioorganic & medicinal chemistry letters, Nov-01, Volume: 21, Issue:21 | Substituted indole-1-acetic acids as potent and selective CRTh2 antagonists-discovery of AZD1981. |
| AID630023 | Inhibition of CYP2D6 | 2011 | Bioorganic & medicinal chemistry letters, Nov-01, Volume: 21, Issue:21 | Substituted indole-1-acetic acids as potent and selective CRTh2 antagonists-discovery of AZD1981. |
| AID630032 | Antagonist activity at prostanoid DP1 receptor | 2011 | Bioorganic & medicinal chemistry letters, Nov-01, Volume: 21, Issue:21 | Substituted indole-1-acetic acids as potent and selective CRTh2 antagonists-discovery of AZD1981. |
| AID630025 | Lipophilicity, log D of the compound at pH 7.4 | 2011 | Bioorganic & medicinal chemistry letters, Nov-01, Volume: 21, Issue:21 | Substituted indole-1-acetic acids as potent and selective CRTh2 antagonists-discovery of AZD1981. |
| AID630028 | Volume of distribution at steady state in Sprague-Dawley rat at 1 mg/kg, iv | 2011 | Bioorganic & medicinal chemistry letters, Nov-01, Volume: 21, Issue:21 | Substituted indole-1-acetic acids as potent and selective CRTh2 antagonists-discovery of AZD1981. |
| AID705353 | Displacement of [3H]PGD2 from recombinant human CRTH2 expressed in HEK293 cells after 2 hrs by microbeta scintillation counting | 2012 | Journal of medicinal chemistry, Apr-12, Volume: 55, Issue:7 | Update on the development of antagonists of chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2). From lead optimization to clinical proof-of-concept in asthma and allergic rhinitis. |
| AID630029 | Half life in Sprague-Dawley rat at 1 mg/kg, iv | 2011 | Bioorganic & medicinal chemistry letters, Nov-01, Volume: 21, Issue:21 | Substituted indole-1-acetic acids as potent and selective CRTh2 antagonists-discovery of AZD1981. |
| AID630021 | Inhibition of CYP2C9 | 2011 | Bioorganic & medicinal chemistry letters, Nov-01, Volume: 21, Issue:21 | Substituted indole-1-acetic acids as potent and selective CRTh2 antagonists-discovery of AZD1981. |
| AID630033 | Inhibition of COX1 assessed as inhibition of arachidonic acid-induced platelet aggregation at >/= 1 uM | 2011 | Bioorganic & medicinal chemistry letters, Nov-01, Volume: 21, Issue:21 | Substituted indole-1-acetic acids as potent and selective CRTh2 antagonists-discovery of AZD1981. |
| AID1346326 | Human DP2 receptor (Prostanoid receptors) | 2011 | Bioorganic & medicinal chemistry letters, Nov-01, Volume: 21, Issue:21 | Substituted indole-1-acetic acids as potent and selective CRTh2 antagonists-discovery of AZD1981. |
| [information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||||
Research
Studies (15)
| 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 | 12 (80.00) | 24.3611 |
| 2020's | 3 (20.00) | 2.80 |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
Study Types
| Publication Type | This drug (%) | All Drugs (%) |
|---|---|---|
| Trials | 7 (46.67%) | 5.53% |
| Reviews | 1 (6.67%) | 6.00% |
| Case Studies | 0 (0.00%) | 4.05% |
| Observational | 0 (0.00%) | 0.25% |
| Other | 7 (46.67%) | 84.16% |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||