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 4-5,7
pEC50 5.9 (EC50 1.34x10-6 M) [4-5,7]
852A Hs Agonist 5.6 pEC50 8
pEC50 5.6 (EC50 2.657x10-6 M) [8]
852A Mm Agonist 5.2 pEC50 8
pEC50 5.2 (EC50 6.224x10-6 M) [8]
imiquimod Hs Agonist 4.9 pEC50 7
pEC50 4.9 (EC50 1.14x10-5 M) [7]
loxoribine Hs Agonist - - 3
[3]
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 6
pIC50 5.6 (IC50 2.78x10-6 M) [6]
Description: Inhibition of hTLR7 R848-induced luciferase reporter gene activation.
Immunopharmacology Comments
TLR7 is an endosomal receptor detecting ssRNA [9]. 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
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. 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]

4. 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]

5. 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]

6. 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]

7. 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.

8. 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]

9. 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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How to cite this page

Clare Bryant, Tom P. Monie.
Toll-like receptor family: TLR7. Last modified on 26/10/2017. Accessed on 23/08/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=1757.