Target Information
| Target General Information | Top | |||||
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| Target ID |
T23666
(Former ID: TTDI02013)
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| Target Name |
Aryl hydrocarbon receptor (AHR)
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| Synonyms |
bHLHe76; Class E basic helixloophelix protein 76; Class E basic helix-loop-helix protein 76; AhR; Ah receptor
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| Gene Name |
AHR
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Thrombocytopenia [ICD-11: 3B64] | |||||
| Function |
Binds to the XRE promoter region of genes it activates. Activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons. Involved in cell-cycle regulation. Likely to play an important role in the development and maturation of many tissues. Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1. Inhibits PER1 by repressing the CLOCK-ARNTL/BMAL1 heterodimer mediated transcriptional activation of PER1. The heterodimer ARNT:AHR binds to core DNA sequence 5'-TGCGTG-3' within the dioxin response element (DRE) of target gene promoters and activates their transcription. Ligand-activated transcriptional activator.
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| UniProt ID | ||||||
| Sequence |
MNSSSANITYASRKRRKPVQKTVKPIPAEGIKSNPSKRHRDRLNTELDRLASLLPFPQDV
INKLDKLSVLRLSVSYLRAKSFFDVALKSSPTERNGGQDNCRAANFREGLNLQEGEFLLQ ALNGFVLVVTTDALVFYASSTIQDYLGFQQSDVIHQSVYELIHTEDRAEFQRQLHWALNP SQCTESGQGIEEATGLPQTVVCYNPDQIPPENSPLMERCFICRLRCLLDNSSGFLAMNFQ GKLKYLHGQKKKGKDGSILPPQLALFAIATPLQPPSILEIRTKNFIFRTKHKLDFTPIGC DAKGRIVLGYTEAELCTRGSGYQFIHAADMLYCAESHIRMIKTGESGMIVFRLLTKNNRW TWVQSNARLLYKNGRPDYIIVTQRPLTDEEGTEHLRKRNTKLPFMFTTGEAVLYEATNPF PAIMDPLPLRTKNGTSGKDSATTSTLSKDSLNPSSLLAAMMQQDESIYLYPASSTSSTAP FENNFFNESMNECRNWQDNTAPMGNDTILKHEQIDQPQDVNSFAGGHPGLFQDSKNSDLY SIMKNLGIDFEDIRHMQNEKFFRNDFSGEVDFRDIDLTDEILTYVQDSLSKSPFIPSDYQ QQQSLALNSSCMVQEHLHLEQQQQHHQKQVVVEPQQQLCQKMKHMQVNGMFENWNSNQFV PFNCPQQDPQQYNVFTDLHGISQEFPYKSEMDSMPYTQNFISCNQPVLPQHSKCTELDYP MGSFEPSPYPTTSSLEDFVTCLQLPENQKHGLNPQSAIITPQTCYAGAVSMYQCQPEPQH THVGQMQYNPVLPGQQAFLNKFQNGVLNETYPAELNNINNTQTTTHLQPLHHPSEARPFP DLTSSGFL Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T84W8G | |||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
| 1 | Romiplostim | Drug Info | Approved | Thrombocytopenia | [2], [3] | |
| Clinical Trial Drug(s) | [+] 3 Clinical Trial Drugs | + | ||||
| 1 | RVT-505 | Drug Info | Phase 2 | Atopic dermatitis | [4] | |
| 2 | BAY 2416964 | Drug Info | Phase 1 | Solid tumour/cancer | [5] | |
| 3 | IK-175 | Drug Info | Phase 1 | Urothelial carcinoma | [6] | |
| Preclinical Drug(s) | [+] 2 Preclinical Drugs | + | ||||
| 1 | 2-(1H-indole-3,-carbonyl)-thiazole-4-carboxylic acid methyl ester | Drug Info | Preclinical | Glioma | [7] | |
| 2 | CB7993113 | Drug Info | Preclinical | Solid tumour/cancer | [8] | |
| Mode of Action | [+] 3 Modes of Action | + | ||||
| Modulator | [+] 2 Modulator drugs | + | ||||
| 1 | Romiplostim | Drug Info | [1], [9] | |||
| 2 | RVT-505 | Drug Info | [4] | |||
| Antagonist | [+] 4 Antagonist drugs | + | ||||
| 1 | BAY 2416964 | Drug Info | [5] | |||
| 2 | IK-175 | Drug Info | [10] | |||
| 3 | CB7993113 | Drug Info | [11] | |||
| 4 | CH-223191 | Drug Info | [13] | |||
| Agonist | [+] 2 Agonist drugs | + | ||||
| 1 | 2-(1H-indole-3,-carbonyl)-thiazole-4-carboxylic acid methyl ester | Drug Info | [7] | |||
| 2 | 6-Formylindolo[3,2-b]carbazole | Drug Info | [12] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Co-Targets | Top | |||||
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| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target-interacting Proteins | ||||||
| References | Top | |||||
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| REF 1 | A Phase I study of the angiogenesis inhibitor SU5416 (semaxanib) in solid tumours, incorporating dynamic contrast MR pharmacodynamic end points. Br J Cancer. 2005 Oct 17;93(8):876-83. | |||||
| REF 2 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6974). | |||||
| REF 3 | 2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6. | |||||
| REF 4 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 5 | ClinicalTrials.gov (NCT04069026) A First-in-Humans Dose Finding Study for an Aryl Hydrocarbon Receptor Inhibitor (AhRi) in Patients With Advanced Cancer. U.S. National Institutes of Health. | |||||
| REF 6 | ClinicalTrials.gov (NCT04200963) A Phase 1a/b Study of IK-175 as a Single Agent and in Combination With Nivolumab in Patients With Locally Advanced or Metastatic Solid Tumors and Urothelial Carcinoma. U.S. National Institutes of Health. | |||||
| REF 7 | 1'H-Indole-3'-Carbonyl-Thiazole-4-Carboxylic Acid Methyl Ester Blocked Human Glioma Cell Invasion via Aryl Hydrocarbon Receptor's Regulation of Cytoskeletal Contraction. Biomed Res Int. 2020 Oct 3;2020:2616930. | |||||
| REF 8 | Tryptophan metabolism as a common therapeutic target in cancer, neurodegeneration and beyond. Nat Rev Drug Discov. 2019 May;18(5):379-401. | |||||
| REF 9 | SU5416, a VEGF Receptor Inhibitor and Ligand of the AHR, Represents a New Alternative for Immunomodulation | |||||
| REF 10 | Clinical pipeline report, company report or official report of Ikena Oncology. | |||||
| REF 11 | In silico identification of an aryl hydrocarbon receptor antagonist with biological activity in vitro and in vivo. Mol Pharmacol. 2014 Nov;86(5):593-608. | |||||
| REF 12 | 6-Formylindolo(3,2-b)carbazole induced aryl hydrocarbon receptor activation prevents intestinal barrier dysfunction through regulation of claudin-2 expression. Chem Biol Interact. 2018 May 25;288:83-90. | |||||
| REF 13 | Novel compound 2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazo-phenyl)-amide (CH-223191) prevents 2,3,7,8-TCDD-induced toxicity by antagonizing the aryl hydrocarbon receptor. Mol Pharmacol. 2006 Jun;69(6):1871-8. | |||||
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