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TLR8

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 1758

Nomenclature: TLR8

Family: Toll-like receptor family

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 1041 Xp22.2 TLR8 toll like receptor 8
Mouse 1 1032 X F5 Tlr8 toll-like receptor 8
Rat - - X Tlr8 toll-like receptor 8
Previous and Unofficial Names Click here for help
toll-like receptor 8 | CD288 | UNQ249/PRO286
Database Links Click here for help
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
UniProtKB
Wikipedia

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
CU-CPT8m Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.7 pKd 8
pKd 6.7 (Kd 2.2x10-7 M) [8]
Description: Dissociation constant measured using isothermal titration calorimetry (ITC) and the hTRL8 ectodomain.
CU-CPT8m Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.2 pIC50 8
pIC50 7.2 (IC50 6.7x10-8 M) [8]
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
motolimod Small molecule or natural product Immunopharmacology Ligand Hs Agonist ~7.0 pEC50 4
pEC50 ~7.0 (EC50 ~1x10-7 M) [4]
selgantolimod Small molecule or natural product Hs Agonist 6.7 pEC50 5
pEC50 6.7 (EC50 2.2x10-7 M) [5]
3M-002 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Immunopharmacology Ligand Hs Agonist 5.9 pEC50 6
pEC50 5.9 (EC50 1.32x10-6 M) [6]
Description: Assessed as ability to activate NF-κB in HEK293 cells expressing human TLR8.
compound 12p [Larson et al., 2017] Small molecule or natural product Primary target of this compound Immunopharmacology Ligand Hs Agonist 5.3 pEC50 2
pEC50 5.3 (EC50 4.98x10-6 M) [2]
Immunopharmacology Comments
TLR8 is an endosomal receptor detecting ssRNA [7]. It may also bind synthetic imidazoquinoline anti-viral drugs. TLR8 signalling is reported to reprogramme the glycolytic metabolic profile of Treg cells, in a mechanism that blocks Treg-induced immunosuppression in the local microenvironment and that can re-activate effective Treg anti-tumour activity [3]. Additional evidence that demonstrates the potential role of TLR8 in immuno-oncology is reviewed in [1]
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 3 GO processes
GO:0045087 innate immune response NAS
GO:0045089 positive regulation of innate immune response IDA
click arrow to show/hide IEA associations
GO:0001774 microglial cell activation IEA
Immuno Process:  T cell (activation)
GO Annotations:  Associated to 1 GO processes
GO:0016064 immunoglobulin mediated immune response TAS
Immuno Process:  B cell (activation)
GO Annotations:  Associated to 1 GO processes
GO:0016064 immunoglobulin mediated immune response TAS
Immuno Process:  Immune regulation
GO Annotations:  Associated to 1 GO processes
GO:0045089 positive regulation of innate immune response IDA
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 1 GO processes
GO:0032755 positive regulation of interleukin-6 production IBA
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 1 GO processes
click arrow to show/hide IEA associations
GO:0001774 microglial cell activation IEA
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Atherosclerosis susceptibility
Disease Ontology: DOID:1936
OMIM: 108725
Disease:  Crimean-Congo hemorrhagic fever
Disease Ontology: DOID:12287
Disease:  Fibrosis
Disease:  Mycobacterium tuberculosis, susceptibility to
Disease Ontology: DOID:399
OMIM: 607948

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. 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, 8 (11): 1148-1152. [PMID:29152046]

3. Li L, Liu X, Sanders KL, Edwards JL, Ye J, Si F, Gao A, Huang L, Hsueh EC, Ford DA et al.. (2019) TLR8-Mediated Metabolic Control of Human Treg Function: A Mechanistic Target for Cancer Immunotherapy. Cell Metab., 29 (1): 103-123.e5. DOI: https://doi.org/10.1016/j.cmet.2018.09.020 [PMID:30344014]

4. Lu H, Dietsch GN, Matthews MA, Yang Y, Ghanekar S, Inokuma M, Suni M, Maino VC, Henderson KE, Howbert JJ et al.. (2012) VTX-2337 is a novel TLR8 agonist that activates NK cells and augments ADCC. Clin. Cancer Res., 18 (2): 499-509. [PMID:22128302]

5. Mackman RL, Mish M, Chin G, Perry JK, Appleby T, Aktoudianakis V, Metobo S, Pyun P, Niu C, Daffis S et al.. (2020) Discovery of GS-9688 (Selgantolimod) as a Potent and Selective Oral Toll-Like Receptor 8 Agonist for the Treatment of Chronic Hepatitis B. J Med Chem, 63 (18): 10188-10203. [PMID:32407112]

6. Salunke DB, Yoo E, Shukla NM, Balakrishna R, Malladi SS, Serafin KJ, Day VW, Wang X, David SA. (2012) Structure-activity relationships in human Toll-like receptor 8-active 2,3-diamino-furo[2,3-c]pyridines. J. Med. Chem., 55 (18): 8137-51. [PMID:22924757]

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

8. Zhang S, Hu Z, Tanji H, Jiang S, Das N, Li J, Sakaniwa K, Jin J, Bian Y, Ohto U et al.. (2018) Small-molecule inhibition of TLR8 through stabilization of its resting state. Nat. Chem. Biol., 14 (1): 58-64. [PMID:29155428]

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