TLR7 | Toll-like receptor family | IUPHAR Guide to IMMUNOPHARMACOLOGY

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TLR7

  Target has curated data in GtoImmuPdb

Target id: 1757

Nomenclature: TLR7

Family: Toll-like receptor family

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 1049 Xp22.3 TLR7 toll like receptor 7
Mouse 1 1050 X 78.31 cM Tlr7 toll-like receptor 7
Rat - - Xq21 Tlr7 toll-like receptor 7
Previous and Unofficial Names
toll-like receptor 7 | UNQ248/PRO285-like
Database Links
CATH/Gene3D
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
UniProtKB
Wikipedia

Download all structure-activity data for this target as a CSV file

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
resiquimod Hs Agonist 5.9 pEC50 5-6,8
pEC50 5.9 (EC50 1.34x10-6 M) [5-6,8]
852A Hs Agonist 5.6 pEC50 9
pEC50 5.6 (EC50 2.657x10-6 M) [9]
852A Mm Agonist 5.2 pEC50 9
pEC50 5.2 (EC50 6.224x10-6 M) [9]
imiquimod Hs Agonist 4.9 pEC50 8
pEC50 4.9 (EC50 1.14x10-5 M) [8]
loxoribine Hs Agonist - - 4
[4]
GSK2245035 Hs Agonist - - 2
[2]
View species-specific agonist tables
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
hydroxychloroquine Hs Antagonist 5.6 pIC50 7
pIC50 5.6 (IC50 2.78x10-6 M) [7]
Description: Inhibition of hTLR7 R848-induced luciferase reporter gene activation.
compound 10a [PMID: 31283223] Hs Antagonist 5.1 pIC50 3
pIC50 5.1 (IC50 8.2x10-6 M) [3]
Immunopharmacology Comments
TLR7 is an endosomal receptor detecting ssRNA [10]. It may also bind synthetic imidazoquinoline anti-viral drugs. The potential role of TLR7 in immuno-oncology is reviewed in [1]
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 8 GO processes
GO:0002224 toll-like receptor signaling pathway IBA
GO:0008329 signaling pattern recognition receptor activity IBA
GO:0034154 toll-like receptor 7 signaling pathway IBA
GO:0034162 toll-like receptor 9 signaling pathway TAS
GO:0050729 positive regulation of inflammatory response IC
click arrow to show/hide IEA associations
GO:0001774 microglial cell activation IEA
GO:0002755 MyD88-dependent toll-like receptor signaling pathway IEA
GO:0045087 innate immune response IEA
Immuno Process:  Immune regulation
GO Annotations:  Associated to 6 GO processes
GO:0002224 toll-like receptor signaling pathway IBA
GO:0008329 signaling pattern recognition receptor activity IBA
GO:0034154 toll-like receptor 7 signaling pathway IBA
GO:0034162 toll-like receptor 9 signaling pathway TAS
GO:0050729 positive regulation of inflammatory response IC
click arrow to show/hide IEA associations
GO:0002755 MyD88-dependent toll-like receptor signaling pathway IEA
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 7 GO processes
GO:0032722 positive regulation of chemokine production IDA
GO:0032755 positive regulation of interleukin-6 production IBA
GO:0032757 positive regulation of interleukin-8 production IDA
GO:0045078 positive regulation of interferon-gamma biosynthetic process IDA
GO:0045356 positive regulation of interferon-alpha biosynthetic process IDA
GO:0045359 positive regulation of interferon-beta biosynthetic process IDA
GO:0045416 positive regulation of interleukin-8 biosynthetic process IMP
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 1 GO processes
GO:0032722 positive regulation of chemokine production IDA
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 6 GO processes
GO:0002224 toll-like receptor signaling pathway IBA
GO:0008329 signaling pattern recognition receptor activity IBA
GO:0034154 toll-like receptor 7 signaling pathway IBA
GO:0034162 toll-like receptor 9 signaling pathway TAS
click arrow to show/hide IEA associations
GO:0001774 microglial cell activation IEA
GO:0002755 MyD88-dependent toll-like receptor signaling pathway IEA
Clinically-Relevant Mutations and Pathophysiology
Disease:  Hepatitis C infection
Disease Ontology: DOID:1883
Disease:  Human immunodeficiency virus type 1, susceptibility to
Synonyms: Human immunodeficiency virus infectious disease [Disease Ontology: DOID:526]
Disease Ontology: DOID:526
OMIM: 609423
Orphanet: ORPHA319269
Disease:  Systemic lupus erythematosus
Description: SLE is a complex autoimmune disease that is characterised by inflammation of various connective tissues, and symptoms include dermatitis, arthritis, inflammation of the kidneys (glomerulonephritis), vasculitis, inflammation of the tissue surrounding the heart, and seizures. It is caused by the production of autoantibodies against widely expressed nuclear, cytoplasmic, and cell surface molecules. Extracellular RNA in the circulation in combination with the presence of autoantibodies potently stimulates interferon production and immune system activation.
Disease Ontology: DOID:9074
OMIM: 152700
Orphanet: ORPHA536

References

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1. Adams JL, Smothers J, Srinivasan R, Hoos A. (2015) Big opportunities for small molecules in immuno-oncology. Nat Rev Drug Discov, 14 (9): 603-22. [PMID:26228631]

2. Biggadike K, Ahmed M, Ball DI, Coe DM, Dalmas Wilk DA, Edwards CD, Gibbon BH, Hardy CJ, Hermitage SA, Hessey JO et al.. (2016) Discovery of 6-Amino-2-{[(1S)-1-methylbutyl]oxy}-9-[5-(1-piperidinyl)pentyl]-7,9-dihydro-8H-purin-8-one (GSK2245035), a Highly Potent and Selective Intranasal Toll-Like Receptor 7 Agonist for the Treatment of Asthma. J. Med. Chem., 59 (5): 1711-26. [PMID:26861551]

3. Bou Karroum N, Moarbess G, Guichou JF, Bonnet PA, Patinote C, Bouharoun-Tayoun H, Chamat S, Cuq P, Diab-Assaf M, Kassab I et al.. (2019) Novel and Selective TLR7 Antagonists among the Imidazo[1,2-a]pyrazines, Imidazo[1,5-a]quinoxalines, and Pyrazolo[1,5-a]quinoxalines Series. J. Med. Chem., [Epub ahead of print]. DOI: 10.1021/acs.jmedchem.9b00411 [PMID:31283223]

4. Heil F, Ahmad-Nejad P, Hemmi H, Hochrein H, Ampenberger F, Gellert T, Dietrich H, Lipford G, Takeda K, Akira S et al.. (2003) The Toll-like receptor 7 (TLR7)-specific stimulus loxoribine uncovers a strong relationship within the TLR7, 8 and 9 subfamily. Eur. J. Immunol., 33 (11): 2987-97. [PMID:14579267]

5. Hemmi H, Kaisho T, Takeuchi O, Sato S, Sanjo H, Hoshino K, Horiuchi T, Tomizawa H, Takeda K, Akira S. (2002) Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. Nat. Immunol., 3 (2): 196-200. [PMID:11812998]

6. Jurk M, Heil F, Vollmer J, Schetter C, Krieg AM, Wagner H, Lipford G, Bauer S. (2002) Human TLR7 or TLR8 independently confer responsiveness to the antiviral compound R-848. Nat. Immunol., 3 (6): 499. [PMID:12032557]

7. Lamphier M, Zheng W, Latz E, Spyvee M, Hansen H, Rose J, Genest M, Yang H, Shaffer C, Zhao Y et al.. (2014) Novel small molecule inhibitors of TLR7 and TLR9: mechanism of action and efficacy in vivo. Mol. Pharmacol., 85 (3): 429-40. [PMID:24342772]

8. Larson P, Kucaba TA, Xiong Z, Olin M, Griffith TS, Ferguson DM. (2017) Design and Synthesis of N1-Modified Imidazoquinoline Agonists for Selective Activation of Toll-like Receptors 7 and 8. ACS Med. Chem. Lett., Epub ahead of print.

9. Nakamura T, Wada H, Kurebayashi H, McInally T, Bonnert R, Isobe Y. (2013) Synthesis and evaluation of 8-oxoadenine derivatives as potent Toll-like receptor 7 agonists with high water solubility. Bioorg. Med. Chem. Lett., 23 (3): 669-72. [PMID:23265901]

10. Uematsu S, Akira S. (2008) Toll-Like receptors (TLRs) and their ligands. Handb Exp Pharmacol, (183): 1-20. [PMID:18071652]

Contributors

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