TLR7

Summary

TLR7 (toll like receptor 7, HGNC:15631) is a protein-coding gene on chromosome Xp22.2, encoding Toll-like receptor 7 (Q9NYK1). Endosomal receptor that plays a key role in innate and adaptive immunity.

The protein encoded by this gene is a member of the Toll-like receptor (TLR) family which plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans and share structural and functional similarities. The human TLR family comprises 11 members. They recognize pathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity. For the recognition of structural components in foreign microorganisms, the various TLRs exhibit different patterns of expression as well; in this way for example, TLR-3, -7, and -8 are essential in the recognition of single-stranded RNA viruses. TLR7 senses single-stranded RNA oligonucleotides containing guanosine- and uridine-rich sequences from RNA viruses, a recognition occuring in the endosomes of plasmacytoid dendritic cells and B cells. This gene is predominantly expressed in lung, placenta, and spleen, and is phylogenetically related and lies in close proximity to another family member, TLR8, on chromosome X.

Source: NCBI Gene 51284 — RefSeq curated summary.

At a glance

• Gene–disease (curated): systemic lupus erythematosus 17 (Moderate, ClinGen) — +2 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 372 total — 5 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 62
• Druggable target: yes — 9 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_016562

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15631
Approved symbol	TLR7
Name	toll like receptor 7
Location	Xp22.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000196664
Ensembl biotype	protein_coding
OMIM	300365
Entrez	51284

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000380659, ENST00000484204

RefSeq mRNA: 1 — MANE Select: NM_016562 NM_016562

CCDS: CCDS14151

Canonical transcript exons

ENST00000380659 — 3 exons

Exon	Start	End
ENSE00001413402	12885512	12890361
ENSE00001485768	12867481	12867581
ENSE00001485772	12867072	12867123

Expression profiles

Bgee: expression breadth ubiquitous, 163 present calls, max score 90.05.

FANTOM5 (CAGE): breadth broad, TPM avg 5.9257 / max 336.8810, expressed in 430 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
195533	4.8506	423
195532	0.6229	228
195531	0.2338	110
195530	0.1821	93
195529	0.0363	19

Top tissues by expression

264 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	90.05	gold quality
mononuclear cell	CL:0000842	89.41	gold quality
leukocyte	CL:0000738	89.18	gold quality
granulocyte	CL:0000094	79.26	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	72.96	silver quality
lymph node	UBERON:0000029	70.57	gold quality
vermiform appendix	UBERON:0001154	70.33	gold quality
gall bladder	UBERON:0002110	70.02	gold quality
parietal pleura	UBERON:0002400	69.50	gold quality
rectum	UBERON:0001052	68.99	gold quality
pleura	UBERON:0000977	68.90	gold quality
right coronary artery	UBERON:0001625	68.23	gold quality
placenta	UBERON:0001987	68.09	gold quality
visceral pleura	UBERON:0002401	67.90	gold quality
blood	UBERON:0000178	67.59	gold quality
palpebral conjunctiva	UBERON:0001812	67.33	gold quality
smooth muscle tissue	UBERON:0001135	66.71	gold quality
epithelium of nasopharynx	UBERON:0001951	65.86	silver quality
caecum	UBERON:0001153	65.40	gold quality
layer of synovial tissue	UBERON:0007616	65.26	silver quality
sperm	CL:0000019	64.38	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	64.28	gold quality
spinal cord	UBERON:0002240	63.53	gold quality
male germ cell	CL:0000015	63.36	gold quality
calcaneal tendon	UBERON:0003701	63.20	gold quality
spleen	UBERON:0002106	62.51	gold quality
colonic epithelium	UBERON:0000397	62.03	silver quality
bone marrow cell	CL:0002092	62.01	silver quality
tonsil	UBERON:0002372	61.88	gold quality
germinal epithelium of ovary	UBERON:0001304	61.08	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.71

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): IRF1, NFKB1, RELA

miRNA regulators (miRDB)

70 targeting TLR7, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-652-5P	99.91	67.49	505
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-1255A	99.74	68.09	744
HSA-MIR-1255B-5P	99.74	68.16	741
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-2682-5P	99.73	67.38	1055
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-548AU-3P	99.70	68.22	1373
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-6848-3P	99.64	66.49	885
HSA-MIR-6513-3P	99.59	69.77	1102
HSA-MIR-7844-5P	99.55	68.56	1428

Literature-anchored findings (GeneRIF, showing 40)

• Human TLR7 or TLR8 independently confer responsiveness to the antiviral compound R-848. (PMID:12032557)
• Interferon-alpha and interleukin-12 are induced differentially by Toll-like receptor 7 ligands in human blood dendritic cell subsets. (PMID:12045249)
• IRF5 and IRF7 are critical mediators of TLR7 signaling (PMID:15695821)
• Plasmacytoid dendritic cell-derived type I IFN enhanced TLR7 sensitivity of B cells by selectively up-regulating TLR7 expression (PMID:15778362)
• TLR7 acts as a host sensor for human parechovirus 1, and activates signalling that leads to the synthesis of pro-inflammatory molecules by the host. (PMID:16025564)
• The agonist isatoribine resulted in dose-dependent changes in immunologic biomarkers and a statistically significant antiviral effect with relatively few and mild side effects in hepatitis C. (PMID:16116638)
• TLR9 may have a critical role in the promotion of lupus through the induction of IFN-alpha by predendritic cells. (PMID:16230478)
• evidence showing that a ligand of Toll-like receptor 7 (TLR7) can induce anti-HCV immunity not only by IFN induction, but also through an IFN-independent mechanism (PMID:16446426)
• TLR-7 “licenses” human B cells to respond to cytokines of the adaptive immune system (such as IL-2) and provide a strategy to increase the immunogenicity of lymphoma cells for therapeutic purposes (PMID:16517754)
• Stimulation of in vitro-generated murine Toll-like receptor 7 (TLR7) knockout DC and human TLR-transfected HEK293 cells with dsRNA fragments gave no evidences for the involvement of pDC-specific TLR7 or TLR9 in the observed IFN-alpha induction. (PMID:16623926)
• A profound sex-dependent pathway of TLR7-induced interferon (IFN)-alpha production is revealed with higher production in females. (PMID:16887967)
• TLR3 agonist poly(I:C) activated epithelial cells, primary endothelial cells, and two types of primary human smooth muscle cells (airway [ASMC] and vascular) directly, while the TLR7/8 agonist R848 required the presence of leukocytes to activate ASMC (PMID:16935934)
• Autoantibody production is largely dependent on Toll-like receptor 7 (TLR7) and causes kidney pathology in nucleic acid-containing autoantigen knockin mice. (PMID:16973388)
• These data lead us to suggest that ongoing viral activation of TLR7/8 could alter the adaptive immune response by modifying DC differentiation and by down-regulating DC responsiveness to a subsequent bacterial TLR4-mediated signal. (PMID:17023556)
• TLR8 inhibits TLR7 and TLR9, and TLR9 inhibits TLR7 but not vice versa in HEK293 cells transfected with TLRs in a pairwise combination. (PMID:17040905)
• results implicate involvement of toll-like receptors, particularly TLR7, and type 1 specific interferon signaling in the pathogenesis of BA, especially in early stage, which is associated with upregulation of inflammatory cytokines IL-8 (PMID:17075576)
• Our data reveal for the first time a strong inhibitory effect of TLR7 stimulation on IFN-alpha production induced by CpG-A- and CpG-C-ODNs. (PMID:17371961)
• The c.1-120G TLR7 allele offers protection from the development of inflammation and fibrosis in male patients with chronic HCV-infection. (PMID:17512627)
• CYLD, a novel deubiquitinase, acts as a negative regulator of TLR7 induction by nontypeable Haemophilus influenzae (PMID:17608805)
• Epstein-Barr virus initially uses TLR7 signaling to enhance B-cell proliferation and subsequently modifies the pathway to regulate IRF-5 activity. (PMID:17609264)
• Both types of compounds induced IFN-gamma-inducible protein 10, but only the 7-deazaguanosine-containing compound that activated both TLR7 and TLR8 induced IFN-alpha in monkeys (PMID:17698957)
• relative gene copy number of TLR7 was not significantly increased among our SLE patients as compared with our controls.No trend between the relative gene copy number and the autoantibody profile in SLE patients. (PMID:17907191)
• IFN-alpha produced after HIV-induced TLR7 stimulation was responsible for TRAIL expression and the down-regulation of both CXCR4 and CCR5 by IKpDC (PMID:17956986)
• Our results show that PAMP receptors, TLR3, TLR7 and RIG-I mRNA levels are significantly down-regulated in patients with chronic hepatitis C infection when compared with healthy controls. (PMID:18021446)
• This study reports the association of TLR7 variants with chronic HCV-infection and with the response to interferon-alpha therapy in patients with chronic HCV-infection. (PMID:18088248)
• There is downregulation of TLR7 expression mRNA in peripheral blood mononuclear cells of hepatitis B virus-infected patients (PMID:18215354)
• Direct involvement of human TLR7 is demonstrated in the induction of tumor necrosis factor (TNF)-alpha by single-stranded RNAs in the macrophage-like THP-1 cell line. (PMID:18250417)
• TLR variants are unlikely to have a major impact on overall AMD risk, and the common variants studied were not associated with AMD. (PMID:18385087)
• TLR7-9 recognize single-stranded RNA, nucleoside analogs and single-stranded CpG-DNA, respectively, and their activation initiates the immune response against viruses and bacteria [review] (PMID:18406377)
• These results delineate the complex effects of triggering TLR7/8 for an efficient antiviral defense. (PMID:18431484)
• TLR-7 signaling stimulates apoptosis resistance, associated with enhanced iNOS expression (protein and mRNA) and NO release, notably through an NF-kappaB-dependent activation of the NO pathway. (PMID:18474259)
• CD300a and CD300c play an important role in the cross-regulation of TNF-alpha and IFN-alpha secretion from pDCs; CD300a/c RNA and surface expression were downregulated after stimulation of pDCs with TLR7 and TLR9 ligands (PMID:18535206)
• the Toll-like receptor 7 agonist imiquimod inhibits melanogenesis and proliferation of human melanocytes (PMID:18596825)
• replicated association was obtained for SNPs or haplotypes of TLR7 and TLR8, suggesting these genes as novel disease genes for asthma and related disorders. (PMID:18682521)
• Human epidermal keratinocytes constitutively express all TLR 1-10 mRNA, which may enable human keratinocytes to respond to a wide range of pathogenic micro-organisms. (PMID:18686608)
• Divergent TLR7 and TLR9 signaling and type I interferon production distinguish pathogenic and nonpathogenic AIDS virus infections. (PMID:18806803)
• Up-regulation of natural killer cell function against head and neck cancer in response to single-stranded immunostimulatory RNA requires TLR7. (PMID:18949362)
• Perturbation of TLR-7 on naive human B cells can lead to the induction of immunoglobulin class switch and IgG production in the absence of B-cell receptor cross-linking and CD40-CD40L interaction. (PMID:18995892)
• inappropriate activation of TLR7 predisposes to systemic lupus erythematosus and other autoimmune diseases; nucleotides with antagonistic effect on TLR7 reported for the treatment (PMID:19120473)
• activation via TLR7 and TLR9 affects several eosinophil functions (PMID:19129482)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tlr7	ENSDARG00000068812
mus_musculus	Tlr7	ENSMUSG00000044583
rattus_norvegicus	Tlr7	ENSRNOG00000004249

Paralogs (22): IGFALS (ENSG00000099769), TLR8 (ENSG00000101916), LRRC17 (ENSG00000128606), RXFP2 (ENSG00000133105), CD180 (ENSG00000134061), TLR4 (ENSG00000136869), TLR2 (ENSG00000137462), LRRC32 (ENSG00000137507), LRRC3 (ENSG00000160233), LRRC53 (ENSG00000162621), TLR3 (ENSG00000164342), VASN (ENSG00000168140), RXFP1 (ENSG00000171509), NRROS (ENSG00000174004), TLR10 (ENSG00000174123), TLR1 (ENSG00000174125), TLR6 (ENSG00000174130), LRRC3B (ENSG00000179796), TSKU (ENSG00000182704), TLR5 (ENSG00000187554), LRIT2 (ENSG00000204033), LRRC3C (ENSG00000204913)

Protein

Protein identifiers

Toll-like receptor 7 — Q9NYK1 (reviewed: Q9NYK1)

All UniProt accessions (2): B2R9N9, Q9NYK1

UniProt curated annotations — full annotation on UniProt →

Function. Endosomal receptor that plays a key role in innate and adaptive immunity. Controls host immune response against pathogens through recognition of uridine-containing single strand RNAs (ssRNAs) of viral origin or guanosine analogs. Upon binding to agonists, undergoes dimerization that brings TIR domains from the two molecules into direct contact, leading to the recruitment of TIR-containing downstream adapter MYD88 through homotypic interaction. In turn, the Myddosome signaling complex is formed involving IRAK4, IRAK1, TRAF6, TRAF3 leading to activation of downstream transcription factors NF-kappa-B and IRF7 to induce pro-inflammatory cytokines and interferons, respectively. In plasmacytoid dendritic cells, RNASET2 endonuclease cooperates with PLD3 or PLD4 5’->3’ exonucleases to process RNA and release 2’,3’-cyclic guanosine monophosphate (2’,3’-cGMP) and cytidine-rich RNA fragments that occupy TLR7 ligand-binding pockets and trigger a signaling-competent state.

Subunit / interactions. Homodimer. Interacts with MYD88 via their respective TIR domains. Interacts with UNC93B1. Interacts with SMPDL3B.

Subcellular location. Endoplasmic reticulum membrane. Endosome. Lysosome. Cytoplasmic vesicle. Phagosome.

Tissue specificity. Detected in brain, placenta, spleen, stomach, small intestine, lung and in plasmacytoid pre-dendritic cells. Expressed in peripheral mononuclear blood cells.

Disease relevance. Immunodeficiency 74, COVID19-related, X-linked (IMD74) [MIM:301051] An X-linked recessive immunologic disorder characterized by impaired type I and type II interferon responses due to defective TLR7 signaling. Individuals with TLR7 deficiency develop severe respiratory insufficiency in response to infection with SARS-CoV-2 coronavirus. Death from respiratory failure may occur. The disease is caused by variants affecting the gene represented in this entry. Systemic lupus erythematosus 17 (SLEB17) [MIM:301080] A form of systemic lupus erythematosus, a chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. SLEB17 is an X-linked dominant form characterized by onset of systemic autoinflammatory symptoms in the first decades of life. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Activated by guanosine analogs including deoxyguanosine, 7-thia-8-oxoguanosine or 7-deazaguanosine in a RNA-independent manner. Activated by imiquimod.

Domain organisation. Contains two binding domains, first site for small ligands and second site for ssRNA.

Similarity. Belongs to the Toll-like receptor family.

RefSeq proteins (1): NP_057646* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000157	TIR_dom	Domain
IPR000483	Cys-rich_flank_reg_C	Domain
IPR001611	Leu-rich_rpt	Repeat
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR035897	Toll_tir_struct_dom_sf	Homologous_superfamily

Pfam: PF01582, PF13855

UniProt features (55 total): repeat 27, glycosylation site 14, sequence variant 6, topological domain 2, sequence conflict 2, signal peptide 1, chain 1, transmembrane region 1, domain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7CYN	ELECTRON MICROSCOPY	4.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NYK1-F1	87.60	0.64

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (14): 66, 69, 167, 202, 215, 361, 413, 488, 523, 534, 590, 679, 720, 799

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-1679131	Trafficking and processing of endosomal TLR
R-HSA-168181	Toll Like Receptor 7/8 (TLR7/8) Cascade
R-HSA-5686938	Regulation of TLR by endogenous ligand
R-HSA-9679191	Potential therapeutics for SARS
R-HSA-9692916	SARS-CoV-1 activates/modulates innate immune responses
R-HSA-9705671	SARS-CoV-2 activates/modulates innate and adaptive immune responses
R-HSA-975110	TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling
R-HSA-975138	TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation
R-HSA-975155	MyD88 dependent cascade initiated on endosome
R-HSA-9824856	Defective regulation of TLR7 by endogenous ligand
R-HSA-9833110	RSV-host interactions

MSigDB gene sets: 459 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_CELLULAR_RESPONSE_TO_VIRUS, REACTOME_INNATE_IMMUNE_SYSTEM, LU_IL4_SIGNALING, GOBP_POSITIVE_REGULATION_OF_TYPE_I_INTERFERON_PRODUCTION, GOBP_INFLAMMATORY_RESPONSE, GOBP_POSITIVE_REGULATION_OF_INTERLEUKIN_8_PRODUCTION, GOCC_VACUOLAR_MEMBRANE, GOBP_CELLULAR_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, BOHN_PRIMARY_IMMUNODEFICIENCY_SYNDROM_DN, GOBP_TOLL_LIKE_RECEPTOR_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_ERYTHROCYTE_UP

GO Biological Process (27): toll-like receptor signaling pathway (GO:0002224), inflammatory response (GO:0006954), canonical NF-kappaB signal transduction (GO:0007249), JNK cascade (GO:0007254), positive regulation of chemokine production (GO:0032722), positive regulation of interferon-alpha production (GO:0032727), positive regulation of interferon-beta production (GO:0032728), positive regulation of type II interferon production (GO:0032729), positive regulation of interleukin-6 production (GO:0032755), positive regulation of interleukin-8 production (GO:0032757), toll-like receptor 7 signaling pathway (GO:0034154), toll-like receptor 8 signaling pathway (GO:0034158), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), innate immune response (GO:0045087), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of inflammatory response (GO:0050729), defense response to virus (GO:0051607), positive regulation of macrophage cytokine production (GO:0060907), response to cGMP (GO:0070305), cellular response to mechanical stimulus (GO:0071260), cellular response to virus (GO:0098586), MAPK cascade (GO:0000165), immune system process (GO:0002376), immune response (GO:0006955), signal transduction (GO:0007165), defense response to other organism (GO:0098542), endolysosomal toll-like receptor signaling pathway (GO:0140894)

GO Molecular Function (5): double-stranded RNA binding (GO:0003725), single-stranded RNA binding (GO:0003727), siRNA binding (GO:0035197), pattern recognition receptor activity (GO:0038187), protein binding (GO:0005515)

GO Cellular Component (15): Golgi membrane (GO:0000139), cytoplasm (GO:0005737), lysosome (GO:0005764), endosome (GO:0005768), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), endosome membrane (GO:0010008), early phagosome (GO:0032009), endolysosome membrane (GO:0036020), signaling receptor complex (GO:0043235), endomembrane system (GO:0012505), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410), phagocytic vesicle (GO:0045335)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Toll-like Receptor Cascades	3
MyD88 dependent cascade initiated on endosome	2
SARS-CoV Infections	1
SARS-CoV-1-host interactions	1
SARS-CoV-2-host interactions	1
Toll Like Receptor 9 (TLR9) Cascade	1
Toll Like Receptor 7/8 (TLR7/8) Cascade	1
Diseases associated with the TLR signaling cascade	1
Respiratory Syncytial Virus Infection Pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of cytokine production	4
cellular anatomical structure	3
defense response	2
positive regulation of type I interferon production	2
endolysosomal toll-like receptor signaling pathway	2
RNA binding	2
bounding membrane of organelle	2
endomembrane system	2
cytoplasm	2
pattern recognition receptor signaling pathway	1
intracellular signaling cassette	1
MAPK cascade	1
chemokine production	1
regulation of chemokine production	1
interferon-alpha production	1
regulation of interferon-alpha production	1
interferon-beta production	1
regulation of interferon-beta production	1
type II interferon production	1
regulation of type II interferon production	1
interleukin-6 production	1
regulation of interleukin-6 production	1
interleukin-8 production	1
regulation of interleukin-8 production	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
immune response	1
defense response to symbiont	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
inflammatory response	1
positive regulation of defense response	1
positive regulation of response to external stimulus	1
regulation of inflammatory response	1
response to virus	1
macrophage cytokine production	1
regulation of macrophage cytokine production	1
positive regulation of myeloid leukocyte cytokine production involved in immune response	1

Protein interactions and networks

STRING

4073 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TLR7	MYD88	P78397	999
TLR7	TLR8	Q9NR97	962
TLR7	UNC93B1	Q9H1C4	956
TLR7	TLR3	O15455	939
TLR7	IRAK1	P51617	939
TLR7	TLR4	O00206	930
TLR7	TLR9	Q9NR96	926
TLR7	IFNA13	P01562	921
TLR7	IRAK4	Q9NWZ3	921
TLR7	IRF7	Q92985	920
TLR7	RIGI	O95786	909
TLR7	HMGB1	P09429	892
TLR7	IFNB1	P01574	888
TLR7	IRF3	Q14653	881
TLR7	IL6	P05231	879

IntAct

15 interactions, top by confidence:

A	B	Type	Score
SIGLEC5	TLR7	psi-mi:“MI:0915”(physical association)	0.400
SIGLEC9	TLR7	psi-mi:“MI:0915”(physical association)	0.400
TLR7	TLR8	psi-mi:“MI:0915”(physical association)	0.400
MLF1	TLR7	psi-mi:“MI:0915”(physical association)	0.400
Hacd3	TLR7	psi-mi:“MI:0915”(physical association)	0.400
TLR7	MLF2	psi-mi:“MI:0915”(physical association)	0.400
PSMD2	TLR7	psi-mi:“MI:0915”(physical association)	0.400
AARSD1	TLR7	psi-mi:“MI:0915”(physical association)	0.400
TLR7	TLR7	psi-mi:“MI:0915”(physical association)	0.370
MYD88	TLR7	psi-mi:“MI:0915”(physical association)	0.370
GRAMD1A	TLR7	psi-mi:“MI:0915”(physical association)	0.370
M		psi-mi:“MI:0914”(association)	0.350
TLR7	A2ML1	psi-mi:“MI:0914”(association)	0.350
	TLR7	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (15): EPDR1 (Affinity Capture-MS), HAL (Affinity Capture-MS), DNAJB9 (Affinity Capture-MS), ALOXE3 (Affinity Capture-MS), SDR9C7 (Affinity Capture-MS), A2ML1 (Affinity Capture-MS), RNF115 (Affinity Capture-Western), TLR7 (Positive Genetic), TLR7 (Cross-Linking-MS (XL-MS)), KIAA2026 (Cross-Linking-MS (XL-MS)), EIF4H (Cross-Linking-MS (XL-MS)), TLR7 (Protein-RNA), TLR7 (Cross-Linking-MS (XL-MS)), TLR7 (Two-hybrid), TLR7 (Two-hybrid)

ESM2 similar proteins: A0N0X6, A4IIW9, B2LT61, B2LT62, B2LT64, B2LT65, B3Y613, B3Y614, B3Y615, B3Y618, B5T267, O60602, O60603, P16235, P30730, P58681, P58682, Q0GC71, Q0ZUL9, Q15399, Q2PZH4, Q2V897, Q32Q07, Q3URE9, Q50L44, Q5M8M9, Q5RDJ4, Q66HV9, Q689D1, Q6GV17, Q6T752, Q704V6, Q7L985, Q8CBC6, Q8N7C0, Q95LA9, Q95M53, Q96FE5, Q9BXR5, Q9D1T0

Diamond homologs: B2LT61, B2LT62, B2LT64, B2LT65, B3Y613, B3Y614, B3Y615, B3Y618, B5T267, O00206, O60603, P0DUE1, P10810, P34595, P58727, Q0GC71, Q0ZUL9, Q13478, Q15399, Q28680, Q2PZH4, Q2V897, Q2V898, Q61098, Q63691, Q689D1, Q68Y56, Q6GV17, Q6R5N8, Q6T752, Q704V6, Q8SPE8, Q8SPE9, Q95LA9, Q95M53, Q9BXR5, Q9DD78, Q9DGB6, Q9EPQ1, Q9EPW9

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
imiquimod	“up-regulates activity”	TLR7	“chemical activation”
resiquimod	“up-regulates activity”	TLR7	“chemical activation”
TLR7	“up-regulates quantity”	IFNA1

Disease & clinical

Clinical variants and AI predictions

ClinVar

372 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	1
Uncertain significance	179
Likely benign	125
Benign	12

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
1330375	NM_016562.4(TLR7):c.1521T>G (p.Phe507Leu)	Pathogenic
1686934	NM_016562.4(TLR7):c.82A>G (p.Arg28Gly)	Pathogenic
4086267	NM_016562.4(TLR7):c.1520T>C (p.Phe507Ser)	Pathogenic
977232	NM_016562.4(TLR7):c.2129_2132del (p.Gln710fs)	Pathogenic
977233	NM_016562.4(TLR7):c.2383G>T (p.Val795Phe)	Pathogenic
4813714	NM_016562.4(TLR7):c.995del (p.Asp332fs)	Likely pathogenic

SpliceAI

209 predictions. Top by Δscore:

Variant	Effect	Δscore
X:12867479:A:AG	acceptor_gain	0.9900
X:12867480:G:GG	acceptor_gain	0.9900
X:12867480:GTT:G	acceptor_gain	0.9900
X:12867582:G:GG	donor_gain	0.9900
X:12867583:T:G	donor_loss	0.9900
X:12885506:TTTCA:T	acceptor_loss	0.9900
X:12885507:TTCA:T	acceptor_loss	0.9900
X:12885508:TCAGG:T	acceptor_loss	0.9900
X:12885509:CAGG:C	acceptor_loss	0.9900
X:12885510:A:C	acceptor_loss	0.9900
X:12885511:GGT:G	acceptor_gain	0.9900
X:12867477:TTAGT:T	acceptor_loss	0.9800
X:12867479:A:G	acceptor_loss	0.9800
X:12867479:AGTT:A	acceptor_gain	0.9800
X:12867480:G:C	acceptor_loss	0.9800
X:12867480:GT:G	acceptor_gain	0.9800
X:12867480:GTTG:G	acceptor_gain	0.9800
X:12867480:GTTGA:G	acceptor_gain	0.9800
X:12870652:C:G	donor_gain	0.9800
X:12885510:A:AG	acceptor_gain	0.9800
X:12885511:G:GG	acceptor_gain	0.9800
X:12889939:T:A	acceptor_gain	0.9800
X:12867121:AAGG:A	donor_loss	0.9600
X:12867122:AG:A	donor_loss	0.9600
X:12867123:GG:G	donor_loss	0.9600
X:12867124:G:GC	donor_loss	0.9600
X:12867125:T:G	donor_loss	0.9600
X:12867119:GAAAG:G	donor_gain	0.9400
X:12867482:T:A	acceptor_gain	0.9400
X:12867579:ATG:A	donor_gain	0.9400

AlphaMissense

6984 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:12886558:T:A	N350K	0.998
X:12886558:T:G	N350K	0.998
X:12886480:C:A	N324K	0.996
X:12886480:C:G	N324K	0.996
X:12886729:C:A	N407K	0.996
X:12886729:C:G	N407K	0.996
X:12888594:T:C	L1029P	0.995
X:12886197:T:C	L230P	0.994
X:12887073:T:C	L522P	0.994
X:12886285:T:A	N259K	0.993
X:12886285:T:G	N259K	0.993
X:12886801:T:A	N431K	0.993
X:12886801:T:G	N431K	0.993
X:12887017:T:A	N503K	0.993
X:12887017:T:G	N503K	0.993
X:12886054:C:A	N182K	0.992
X:12886054:C:G	N182K	0.992
X:12886470:T:C	L321P	0.992
X:12888227:T:A	W907R	0.992
X:12888227:T:C	W907R	0.992
X:12886269:T:C	L254P	0.991
X:12886464:T:C	L319P	0.991
X:12887385:T:C	F626S	0.991
X:12888229:G:C	W907C	0.991
X:12888229:G:T	W907C	0.991
X:12888356:A:C	S950R	0.991
X:12888358:C:A	S950R	0.991
X:12888358:C:G	S950R	0.991
X:12886275:T:C	L256P	0.990
X:12886398:T:C	L297P	0.990

dbSNP variants (sampled 300 via entrez): RS1000192123 (X:12883265 T>C), RS1000196064 (X:12865146 C>T), RS1000244111 (X:12882712 C>T), RS1000292689 (X:12872154 G>A), RS1001405175 (X:12884040 T>C), RS1001491067 (X:12889850 A>T), RS1001622303 (X:12865704 G>A), RS1001665522 (X:12882788 C>T), RS1001696286 (X:12871630 C>A,G), RS1001960719 (X:12867573 C>T), RS1001999350 (X:12884472 C>A,T), RS1002055318 (X:12870527 A>C), RS1002253188 (X:12867194 G>A), RS1002313904 (X:12876119 C>A,T), RS1002410661 (X:12881467 AAAT>A)

Disease associations

OMIM: gene MIM:300365 | disease phenotypes: MIM:152700, MIM:601744, MIM:301080, MIM:301051

GenCC curated gene-disease

Disease	Classification	Inheritance
immunodeficiency 74, COVID-19-related, X-linked	Moderate	X-linked
systemic lupus erythematosus 17	Moderate	X-linked
systemic lupus erythematosus	Supportive	Unknown

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
systemic lupus erythematosus 17	Moderate	XL

Mondo (3): systemic lupus erythematosus (MONDO:0007915), systemic lupus erythematosus 17 (MONDO:0859083), immunodeficiency 74, COVID-19-related, X-linked (MONDO:0026767)

Orphanet (1): Systemic lupus erythematosus (Orphanet:536)

HPO phenotypes

62 total (30 of 62 shown, HPO-id order):

HPO	Term
HP:0000093	Proteinuria
HP:0000155	Oral ulcer
HP:0000488	Retinopathy
HP:0000716	Depression
HP:0000739	Anxiety
HP:0000790	Hematuria
HP:0000822	Hypertension
HP:0000992	Cutaneous photosensitivity
HP:0001250	Seizure
HP:0001369	Arthritis
HP:0001419	X-linked recessive inheritance
HP:0001423	X-linked dominant inheritance
HP:0001596	Alopecia
HP:0001653	Mitral regurgitation
HP:0001824	Weight loss
HP:0001873	Thrombocytopenia
HP:0001878	Hemolytic anemia
HP:0001882	Decreased total leukocyte count
HP:0001888	Decreased total lymphocyte count
HP:0001945	Fever
HP:0001954	Recurrent fever
HP:0001973	Autoimmune thrombocytopenia
HP:0002039	Anorexia
HP:0002072	Chorea
HP:0002315	Headache
HP:0002716	Lymphadenopathy
HP:0002725	Systemic lupus erythematosus
HP:0002829	Arthralgia
HP:0003453	Antineutrophil antibody positivity
HP:0003493	Antinuclear antibody positivity

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST000612_1	Celiac disease	6.000000e-08

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008180	Lupus Erythematosus, Systemic	C17.300.480; C20.111.590

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2111471 (PROTEIN FAMILY), CHEMBL3137288 (PROTEIN FAMILY), CHEMBL5936 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

9 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 121,195 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1282	IMIQUIMOD	4	56,604
CHEMBL1535	HYDROXYCHLOROQUINE	4	42,638
CHEMBL2424780	VESATOLIMOD	2	1,766
CHEMBL383322	RESIQUIMOD	2	18,616
CHEMBL4297492	GSK-2245035	2	809
CHEMBL4650329	AFIMETORAN	2	49
CHEMBL5417170	MHV-370	2	26
CHEMBL549344	CPG-52852	2	659
CHEMBL5314554	GURETOLIMOD	1	28

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs179008	Efficacy	3	imiquimod	Basal Cell Carcinoma

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs179008	TLR7	3	2.50	1	imiquimod

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — Toll-like receptor family

Most potent curated ligand interactions (7 total), top 7:

Ligand	Action	Affinity	Parameter
enpatoran	Antagonist	6.0	pIC50
resiquimod	Agonist	5.87	pEC50
852A	Agonist	5.58	pEC50
hydroxychloroquine	Antagonist	5.56	pIC50
compound 10a [PMID: 31283223]	Antagonist	5.09	pIC50
imiquimod	Agonist	4.94	pEC50
compound 27 [WO2019226977A1]	Agonist	3.42	pEC50

Binding affinities (BindingDB)

2002 measured of 2097 human assays (2097 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-[4-[2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-3-propan-2-yl-1H-pyrrolo[3,2-b]pyridin-5-yl]cyclohexyl]oxolan-3-amine	IC50	0.08 nM	US-10544143: 4-azaindole compounds
3-[4-[2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-indol-5-yl]piperidin-1-yl]pentane-1,5-diol	IC50	0.1 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
2-(dimethylamino)-1-[(3R)-4-[2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-pyrrolo[3,2-b]pyridin-5-yl]-3-methylpiperazin-1-yl]ethanone	IC50	0.19 nM	US-10544143: 4-azaindole compounds
2-[4-[2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-indol-5-yl]piperidin-1-yl]-1-pyrrolidin-1-ylethanone	IC50	0.2 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
8-chloro-7-methyl-6-(5-piperidin-4-yl-3-propan-2-yl-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine	IC50	0.2 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
1-[4-[2-(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-indol-5-yl]piperidin-1-yl]-2-methylpropan-2-ol	IC50	0.2 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
8-methoxy-6-[5-[1-(2-methylsulfonylethyl)piperidin-4-yl]-3-propan-2-yl-1H-indol-2-yl]-[1,2,4]triazolo[1,5-a]pyridine	IC50	0.2 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
2-[4-[2-(8-cyclopropyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-indol-5-yl]piperidin-1-yl]-N-methylacetamide	IC50	0.2 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
3-[4-[2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-indol-5-yl]piperidin-1-yl]propan-1-ol	IC50	0.2 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
2-(dimethylamino)-1-[4-[3-propan-2-yl-2-[8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl]-1H-indol-5-yl]piperidin-1-yl]ethanone	IC50	0.2 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
1-[4-[2-(8-cyclopropyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-indol-5-yl]piperidin-1-yl]-2-(dimethylamino)ethanone	IC50	0.2 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
1-[4-[2-(8-cyclopropyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-indol-5-yl]piperidin-1-yl]-2-(methylamino)ethanone	IC50	0.2 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
2-[cyclopropyl(2-hydroxyethyl)amino]-1-[4-[2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-indol-5-yl]piperidin-1-yl]ethanone	IC50	0.2 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
1-[4-[2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-indol-5-yl]piperidin-1-yl]-2-[methyl(propan-2-yl)amino]ethanone	IC50	0.2 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
1-(3,3-difluoroazetidin-1-yl)-2-[4-[2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-indol-5-yl]piperidin-1-yl]ethanone	IC50	0.2 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
2-[[3-[4-[2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-indol-5-yl]piperidin-1-yl]-3-oxopropyl]amino]acetamide	IC50	0.2 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
1-[(2R,5S)-4-[2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-pyrrolo[3,2-b]pyridin-5-yl]-2,5-dimethylpiperazin-1-yl]-3-(1-oxa-6-azaspiro[3.3]heptan-6-yl)propan-1-one	IC50	0.27 nM	US-10544143: 4-azaindole compounds
6-[5-[(2S,5S)-2,5-dimethylpiperazin-1-yl]-3-propan-2-yl-1H-pyrrolo[3,2-b]pyridin-2-yl]-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine	IC50	0.27 nM	US-10544143: 4-azaindole compounds
2-(dimethylamino)-1-[(2S,6R)-4-[2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-pyrrolo[3,2-b]pyridin-5-yl]-2,6-dimethylpiperazin-1-yl]ethanone	IC50	0.29 nM	US-10544143: 4-azaindole compounds
6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine dihydrochloride	IC50	0.3 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
6-[5-[1-(isocyanomethyl)piperidin-4-yl]-3-propan-2-yl-1H-indol-2-yl]-8-methyl-[1,2,4]triazolo[1,5-a]pyridine	IC50	0.3 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
2-[4-[2-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-indol-5-yl]piperidin-1-yl]acetamide	IC50	0.3 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
2-(4-(3-isopropyl-2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-indol-5-yl)piperidin-1-yl)-N,N-dimethylacetamide	IC50	0.3 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
8-methyl-6-[5-[1-(2-methylpropyl)piperidin-4-yl]-3-propan-2-yl-1H-indol-2-yl]-[1,2,4]triazolo[1,5-a]pyridine	IC50	0.3 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
8-methoxy-6-[5-[1-(oxan-4-yl)piperidin-4-yl]-3-propan-2-yl-1H-indol-2-yl]-[1,2,4]triazolo[1,5-a]pyridine	IC50	0.3 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
8-ethyl-6-(3-isopropyl-5-(piperidin-4-yl)-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine	IC50	0.3 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
8-chloro-2,7-dimethyl-6-(5-piperidin-4-yl-3-propan-2-yl-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine	IC50	0.3 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
8-cyclopropyl-6-(5-piperidin-4-yl-3-propan-2-yl-1H-indol-2-yl)-[1,2,4]triazolo[1,5-a]pyridine	IC50	0.3 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
2-[4-[2-(8-cyclopropyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-indol-5-yl]piperidin-1-yl]-N,N-dimethylacetamide	IC50	0.3 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
8-methyl-6-[5-[1-(oxolan-3-yl)piperidin-4-yl]-3-propan-2-yl-1H-indol-2-yl]-[1,2,4]triazolo[1,5-a]pyridine	IC50	0.3 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
6-[5-[1-[(3-methyloxetan-3-yl)methyl]piperidin-4-yl]-3-propan-2-yl-1H-indol-2-yl]-8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridine	IC50	0.3 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
8-methoxy-6-[5-[1-[(3-methyloxetan-3-yl)methyl]piperidin-4-yl]-3-propan-2-yl-1H-indol-2-yl]-[1,2,4]triazolo[1,5-a]pyridine	IC50	0.3 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
2-(methylamino)-1-[4-[3-propan-2-yl-2-[8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl]-1H-indol-5-yl]piperidin-1-yl]ethanone	IC50	0.3 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
2-[ethyl(methyl)amino]-1-[4-[3-propan-2-yl-2-[8-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl]-1H-indol-5-yl]piperidin-1-yl]ethanone	IC50	0.3 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
2-[4-[2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-indol-5-yl]piperidin-1-yl]-N-[(3-methyloxetan-3-yl)methyl]acetamide	IC50	0.3 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
3-(dimethylamino)-1-[(2S,6R)-4-[2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-pyrrolo[3,2-b]pyridin-5-yl]-2,6-dimethylpiperazin-1-yl]propan-1-one	IC50	0.3 nM	US-10544143: 4-azaindole compounds
6-[5-[(2R,6R)-2,6-dimethylpiperazin-1-yl]-3-propan-2-yl-1H-pyrrolo[3,2-b]pyridin-2-yl]-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine	IC50	0.31 nM	US-10544143: 4-azaindole compounds
[(2S)-1-[4-[2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-pyrrolo[3,2-b]pyridin-5-yl]cyclohexyl]pyrrolidin-2-yl]methanol	IC50	0.34 nM	US-10544143: 4-azaindole compounds
1-[(2R,5S)-4-[2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-pyrrolo[3,2-b]pyridin-5-yl]-2,5-dimethylpiperazin-1-yl]-2-[ethyl(methyl)amino]ethanone	IC50	0.34 nM	US-10544143: 4-azaindole compounds
1-[(2R,5S)-4-[2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-pyrrolo[3,2-b]pyridin-5-yl]-2,5-dimethylpiperazin-1-yl]-3-(2-oxa-7-azaspiro[3.4]octan-7-yl)propan-1-one	IC50	0.35 nM	US-10544143: 4-azaindole compounds
3-(dimethylamino)-1-[(3S)-4-[2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-pyrrolo[3,2-b]pyridin-5-yl]-3-methylpiperazin-1-yl]propan-1-one	IC50	0.36 nM	US-10544143: 4-azaindole compounds
6-[5-[(2S)-2-ethylpiperazin-1-yl]-3-propan-2-yl-1H-pyrrolo[3,2-b]pyridin-2-yl]-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine	IC50	0.36 nM	US-10544143: 4-azaindole compounds
2-(dimethylamino)-1-[(2S,5R)-4-[2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-pyrrolo[3,2-b]pyridin-5-yl]-2,5-dimethylpiperazin-1-yl]ethanone	IC50	0.37 nM	US-10544143: 4-azaindole compounds
1-[(2R,5S)-4-[2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-pyrrolo[3,2-b]pyridin-5-yl]-2,5-dimethylpiperazin-1-yl]-2-[methyl(propyl)amino]ethanone	IC50	0.37 nM	US-10544143: 4-azaindole compounds
2-(dimethylamino)-1-[(3S,5S)-4-[2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-pyrrolo[3,2-b]pyridin-5-yl]-3,5-dimethylpiperazin-1-yl]ethanone	IC50	0.38 nM	US-10544143: 4-azaindole compounds
3-(dimethylamino)-1-[(2S,5R)-4-[2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-pyrrolo[3,2-b]pyridin-5-yl]-2,5-dimethylpiperazin-1-yl]propan-1-one	IC50	0.38 nM	US-10544143: 4-azaindole compounds
2-(dimethylamino)-1-[(2R,5S)-4-[2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-pyrrolo[3,2-b]pyridin-5-yl]-2,5-dimethylpiperazin-1-yl]ethanone	IC50	0.38 nM	US-10544143: 4-azaindole compounds
1-[(2R,5S)-4-[2-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-pyrrolo[3,2-b]pyridin-5-yl]-2,5-dimethylpiperazin-1-yl]-3-[ethyl(methyl)amino]propan-1-one	IC50	0.39 nM	US-10544143: 4-azaindole compounds
2-[4-[2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-indol-5-yl]piperidin-1-yl]-N-methylacetamide	IC50	0.4 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds
1-[4-[2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-propan-2-yl-1H-indol-5-yl]piperidin-1-yl]-2-methylpropan-2-ol	IC50	0.4 nM	US-10071079: [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 44 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.15	EC50	0.07	nM	CHEMBL5266091
10.10	IC50	0.08	nM	CHEMBL5751106
10.10	IC50	0.08	nM	CHEMBL5885111
10.05	IC50	0.09	nM	CHEMBL5858961
10.00	IC50	0.1	nM	CHEMBL5079910
10.00	IC50	0.1	nM	CHEMBL5940072
9.96	EC50	0.11	nM	CHEMBL5267703
9.92	IC50	0.12	nM	CHEMBL5921788
9.89	IC50	0.13	nM	CHEMBL5998206
9.85	IC50	0.14	nM	CHEMBL5976680
9.80	IC50	0.16	nM	CHEMBL5897666
9.77	IC50	0.17	nM	CHEMBL5875231
9.77	IC50	0.17	nM	CHEMBL5873838
9.74	IC50	0.18	nM	CHEMBL5915096
9.72	IC50	0.19	nM	CHEMBL5925587
9.72	IC50	0.19	nM	CHEMBL5802160
9.70	IC50	0.2	nM	CHEMBL5824058
9.70	IC50	0.2	nM	CHEMBL5821604
9.70	IC50	0.2	nM	CHEMBL5817501
9.70	IC50	0.2	nM	CHEMBL5847695
9.70	IC50	0.2	nM	CHEMBL5971057
9.70	IC50	0.2	nM	CHEMBL6035407
9.70	IC50	0.2	nM	CHEMBL5765718
9.70	IC50	0.2	nM	CHEMBL6045270
9.70	IC50	0.2	nM	CHEMBL5992367
9.70	IC50	0.2	nM	CHEMBL6049483
9.70	IC50	0.2	nM	CHEMBL5886174
9.70	IC50	0.2	nM	CHEMBL5939754
9.70	IC50	0.2	nM	CHEMBL5837680
9.70	IC50	0.2	nM	CHEMBL5772569
9.70	IC50	0.2	nM	CHEMBL5926258
9.70	EC50	0.2	nM	CHEMBL1836893
9.68	IC50	0.21	nM	CHEMBL6051658
9.68	IC50	0.21	nM	CHEMBL5982619
9.66	IC50	0.22	nM	CHEMBL5804883
9.62	EC50	0.24	nM	CHEMBL5277999
9.62	IC50	0.24	nM	CHEMBL5919009
9.60	IC50	0.25	nM	CHEMBL6045093
9.59	IC50	0.26	nM	CHEMBL6048002
9.57	EC50	0.27	nM	CHEMBL5273537
9.57	IC50	0.27	nM	CHEMBL5931592
9.57	IC50	0.27	nM	CHEMBL5797419
9.57	IC50	0.27	nM	CHEMBL5835698
9.57	IC50	0.27	nM	CHEMBL6024977

PubChem BioAssay actives

1297 with measured affinity, of 2998 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
5-cyclopropyl-6-(3-fluoro-2-methyl-4-pyridinyl)-N-[(3S,4S)-3-fluoropiperidin-4-yl]-1H-indazol-3-amine	1827792: Antagonist activity at human TLR7 expressed in human PBMC cells assessed as inhibition of ssRNA stimulated IFNalpha level preincubated for 30 mins followed by stimulation and measured after 20 hrs by AlphaLISA method	ic50	0.0001	uM
2-[3-methyl-4-propan-2-yl-5-(3,5,6-triazatricyclo[7.3.0.02,6]dodeca-1(9),2,4,7-tetraen-8-yl)-6H-thieno[2,3-b]pyrrol-2-yl]-5-oxa-8-azaspiro[3.5]nonane	1956347: Antagonist activity at human TLR7 expressed in human PBMC cells preincubated for 1 hr followed by GS-986 stimulation measured after 6 hrs by electrochemiluminescence immunoassay	ec50	0.0001	uM
2-[(1S,4R,5R)-5-[3-methyl-5-(4-methyl-3,5,6-triazatricyclo[7.3.0.02,6]dodeca-1(9),2,4,7-tetraen-8-yl)-4-propan-2-yl-6H-thieno[2,3-b]pyrrol-2-yl]-2-azabicyclo[2.2.1]heptan-2-yl]acetamide	1956347: Antagonist activity at human TLR7 expressed in human PBMC cells preincubated for 1 hr followed by GS-986 stimulation measured after 6 hrs by electrochemiluminescence immunoassay	ec50	0.0002	uM
4-amino-1-[[6-(2-piperidin-1-ylethylamino)-3-pyridinyl]methyl]-6-(trifluoromethyl)-3H-imidazo[4,5-c]pyridin-2-one	622817: Agonist activity at TLR7	ec50	0.0002	uM
3-methyl-4-propan-2-yl-2-(5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)-5-(3,5,6-triazatricyclo[7.3.0.02,6]dodeca-1(9),2,4,7-tetraen-8-yl)-6H-thieno[2,3-b]pyrrole	1956347: Antagonist activity at human TLR7 expressed in human PBMC cells preincubated for 1 hr followed by GS-986 stimulation measured after 6 hrs by electrochemiluminescence immunoassay	ec50	0.0003	uM
3-methyl-2-[(1S,4R,5R)-2-(2-methylsulfonylethyl)-2-azabicyclo[2.2.1]heptan-5-yl]-4-propan-2-yl-5-(3,5,6-triazatricyclo[7.3.0.02,6]dodeca-1(9),2,4,7-tetraen-8-yl)-6H-thieno[2,3-b]pyrrole	1956347: Antagonist activity at human TLR7 expressed in human PBMC cells preincubated for 1 hr followed by GS-986 stimulation measured after 6 hrs by electrochemiluminescence immunoassay	ec50	0.0003	uM
5-cyclopropyl-6-(3-fluoro-2-methyl-4-pyridinyl)-N-(1-methylpiperidin-4-yl)-1H-indazol-3-amine	1827792: Antagonist activity at human TLR7 expressed in human PBMC cells assessed as inhibition of ssRNA stimulated IFNalpha level preincubated for 30 mins followed by stimulation and measured after 20 hrs by AlphaLISA method	ic50	0.0004	uM
4-amino-1-[[6-[methyl-[2-(4-methylpiperazin-1-yl)ethyl]amino]-3-pyridinyl]methyl]-6-(trifluoromethyl)-3H-imidazo[4,5-c]pyridin-2-one	622817: Agonist activity at TLR7	ec50	0.0004	uM
N-[4-[[5-(1,6-dimethylpyrazolo[3,4-b]pyridin-4-yl)-3-methyl-6,7-dihydro-4H-pyrazolo[4,5-c]pyridin-1-yl]methyl]-1-bicyclo[2.2.2]octanyl]-2-[ethyl(methyl)amino]acetamide	1846688: Antagonist activity at TLR7 in human PBMC incubated for 3 hrs by TR-FRET assay	ic50	0.0005	uM
2-(6-azaspiro[3.4]octan-2-yl)-3-methyl-4-propan-2-yl-5-(3,5,6-triazatricyclo[7.3.0.02,6]dodeca-1(9),2,4,7-tetraen-8-yl)-6H-thieno[2,3-b]pyrrole	1956347: Antagonist activity at human TLR7 expressed in human PBMC cells preincubated for 1 hr followed by GS-986 stimulation measured after 6 hrs by electrochemiluminescence immunoassay	ec50	0.0005	uM
6-amino-2-[(2S)-butan-2-yl]oxy-9-(5-piperidin-1-ylpentyl)-7H-purin-8-one	1949280: Agonist activity at TLR7 in human PBMC assessed as IFN-alpha production after 24 hrs by electrochemiluminescence assay	ec50	0.0005	uM
5-[(5,6-dimethoxy-2-pyridinyl)methyl]-4-N-[(5-methyl-1,2-oxazol-3-yl)methyl]pyrrolo[3,2-d]pyrimidine-2,4-diamine	1475526: Agonist activity at TLR7 in human PBMC assessed as induction of IFNalpha-mediated inhibition of HCV genotype 1b RNA replication in human HuH luc/neo replicon cells after 24 hrs by luciferase reporter gene assay	ec50	0.0006	uM
8-[2-[(3S,4S)-3-fluoropiperidin-4-yl]-7-(trifluoromethyl)indazol-5-yl]-2,3-dihydro-1H-indolizin-5-one	1661554: Antagonist activity at TLR7 in human PBMC assessed as inhibition of DOTAP-ssRNA40 induced IFNalpha production preincubated for 30 mins followed by ssRNA40 addition measured after 20 hrs by alphaLISA	ic50	0.0006	uM
6-amino-2-[(2S)-hexan-2-yl]oxy-9-(4-piperidin-1-ylbutyl)-7H-purin-8-one	1949280: Agonist activity at TLR7 in human PBMC assessed as IFN-alpha production after 24 hrs by electrochemiluminescence assay	ec50	0.0006	uM
6-amino-2-butoxy-9-(4-piperidin-4-ylbutyl)-7H-purin-8-one	1949280: Agonist activity at TLR7 in human PBMC assessed as IFN-alpha production after 24 hrs by electrochemiluminescence assay	ec50	0.0006	uM
2-(2,6-dimethyl-4-pyridinyl)-5-piperidin-4-yl-3-propan-2-yl-1H-indole	1880294: Antagonist activity at gardiquimod stimulated human TRL7 overexpressed in HEK293 cells assessed as inhibition of NF kappa B/Ap-1 activation preincubated with compound for 30 mins followed by gardiquimod stimulation measured after 22 hrs by SEAP reporter assay	ic50	0.0007	uM
6-(3-fluoro-2-methyl-4-pyridinyl)-5-methoxy-N-(1-methylpiperidin-4-yl)-1H-indazol-3-amine	1827792: Antagonist activity at human TLR7 expressed in human PBMC cells assessed as inhibition of ssRNA stimulated IFNalpha level preincubated for 30 mins followed by stimulation and measured after 20 hrs by AlphaLISA method	ic50	0.0007	uM
6-fluoro-2-(2-methyl-4-pyridinyl)-5-piperidin-4-yl-3-propan-2-yl-1H-indole	1880294: Antagonist activity at gardiquimod stimulated human TRL7 overexpressed in HEK293 cells assessed as inhibition of NF kappa B/Ap-1 activation preincubated with compound for 30 mins followed by gardiquimod stimulation measured after 22 hrs by SEAP reporter assay	ic50	0.0008	uM
2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3,4-dimethyl-6-piperidin-4-yl-9H-carbazole	1768800: Inhibition of human TLR7 in HEK-Blue hTLR7 cells assessed as reduction in gardiquimod-activated NF-KappaB by SEAP reporter assay	ic50	0.0008	uM
6-amino-2-[(2S)-pentan-2-yl]oxy-9-(4-piperidin-1-ylbutyl)-7H-purin-8-one	1949280: Agonist activity at TLR7 in human PBMC assessed as IFN-alpha production after 24 hrs by electrochemiluminescence assay	ec50	0.0008	uM
6-amino-2-butoxy-9-[4-(1-propan-2-ylpiperidin-4-yl)butyl]-7H-purin-8-one	1949280: Agonist activity at TLR7 in human PBMC assessed as IFN-alpha production after 24 hrs by electrochemiluminescence assay	ec50	0.0008	uM
2-(2,6-dimethyl-4-pyridinyl)-4-fluoro-5-piperidin-4-yl-3-propan-2-yl-1H-indole	1880294: Antagonist activity at gardiquimod stimulated human TRL7 overexpressed in HEK293 cells assessed as inhibition of NF kappa B/Ap-1 activation preincubated with compound for 30 mins followed by gardiquimod stimulation measured after 22 hrs by SEAP reporter assay	ic50	0.0009	uM
6-amino-2-[(2S)-pentan-2-yl]oxy-9-(5-piperidin-1-ylpentyl)-7H-purin-8-one	1949283: Agonist activity at TLR7 in human whole blood assessed as induction of IFNalpha production after 20 hrs by electrochemiluminescence assay	ec50	0.0009	uM
5-[(6-methoxy-2-pyridinyl)methyl]-4-N-[(5-methyl-1,2-oxazol-3-yl)methyl]pyrrolo[3,2-d]pyrimidine-2,4-diamine	1475526: Agonist activity at TLR7 in human PBMC assessed as induction of IFNalpha-mediated inhibition of HCV genotype 1b RNA replication in human HuH luc/neo replicon cells after 24 hrs by luciferase reporter gene assay	ec50	0.0010	uM
4-amino-2-butoxy-7-[[6-(pyrrolidin-1-ylmethyl)-3-pyridinyl]methyl]-5H-pyrrolo[3,2-d]pyrimidine-6-carbonitrile	1940775: Agonist activity at TLR7 (unknown origin)	ec50	0.0010	uM
16-amino-6-[4-[(cyclobutylamino)methyl]phenyl]-8,13-dioxa-1,15,18,21-tetrazatetracyclo[12.5.2.13,7.017,20]docosa-3(22),4,6,14,16,20-hexaen-19-one	1940779: Agonist activity at human TLR7 in HEK-Blue hTLR7 cells incubated for 18 hrs by quanti-blue reagent based analysis	ec50	0.0010	uM
4-[[3-methyl-5-(1H-pyrazolo[3,4-b]pyridin-4-yl)-2-pyridinyl]oxymethyl]bicyclo[2.2.2]octan-1-amine	1721815: Antagonist activity at TLR7 in human PBMC assessed as inhibition of ssRNA40-induced IFNalpha production	ic50	0.0010	uM
2-deuterio-5-[(2S,6R)-6-methyl-11-piperidin-4-yloxy-4,7,10-triazatricyclo[7.4.0.02,7]trideca-1(9),10,12-trien-4-yl]quinoline-8-carbonitrile	1777159: Inhibition of human TLR7 expressed in HEK293-Blue cells assessed as inhibition of R848-induced NF-kappaB/AP-1 activation measured after 20 hrs using quanti-blue as substrate by SEAP reporter gene based spectrophotometry assay	ic50	0.0010	uM
4-[[5-(1,6-dimethylpyrazolo[3,4-b]pyridin-4-yl)-3-methyl-2-pyridinyl]oxymethyl]bicyclo[2.2.2]octan-1-amine	1721815: Antagonist activity at TLR7 in human PBMC assessed as inhibition of ssRNA40-induced IFNalpha production	ic50	0.0010	uM
3-[6-[(4-amino-1-bicyclo[2.2.2]octanyl)methoxy]-5-methyl-3-pyridinyl]-1-methylpyrazolo[3,4-d]pyrimidin-6-amine	1721815: Antagonist activity at TLR7 in human PBMC assessed as inhibition of ssRNA40-induced IFNalpha production	ic50	0.0010	uM
6-(3-fluoro-2-methyl-4-pyridinyl)-5-methyl-N-(1-methylpiperidin-4-yl)-1H-indazol-3-amine	1827792: Antagonist activity at human TLR7 expressed in human PBMC cells assessed as inhibition of ssRNA stimulated IFNalpha level preincubated for 30 mins followed by stimulation and measured after 20 hrs by AlphaLISA method	ic50	0.0010	uM
6-amino-9-[[6-[2-(dimethylamino)ethoxy]-3-pyridinyl]methyl]-2-[ethyl(methyl)phosphoryl]-7H-purin-8-one	2035519: Agonist activity at TLR7 in human HEK-Blue hTLR7 cells assessed as activation of NF-kappaB incubated for 20 hrs by SEAP reporter gene based quanti-blue reagent spectrophotometric analysis	ec50	0.0010	uM
2-(azetidin-1-yl)-N-[4-[[5-(1,6-dimethylpyrazolo[3,4-b]pyridin-4-yl)-3-methyl-6,7-dihydro-4H-pyrazolo[4,5-c]pyridin-1-yl]methyl]-1-bicyclo[2.2.2]octanyl]acetamide	2011578: Antagonist activity at TLR7 in human PBMC cells assessed as reduction in IFN alpha measured after 20 hrs by AlphaLISA assay	ic50	0.0010	uM
4-amino-1-[[6-[2-(diethylamino)ethyl-methylamino]-3-pyridinyl]methyl]-6-(trifluoromethyl)-3H-imidazo[4,5-c]pyridin-2-one	622817: Agonist activity at TLR7	ec50	0.0010	uM
6-amino-9-(5-piperidin-1-ylpentyl)-2-propan-2-yloxy-7H-purin-8-one	1949280: Agonist activity at TLR7 in human PBMC assessed as IFN-alpha production after 24 hrs by electrochemiluminescence assay	ec50	0.0010	uM
[6-(2,6-dimethyl-4-pyridinyl)-5-methoxy-1H-indazol-3-yl]-(4-methylpiperazin-1-yl)methanone	1827792: Antagonist activity at human TLR7 expressed in human PBMC cells assessed as inhibition of ssRNA stimulated IFNalpha level preincubated for 30 mins followed by stimulation and measured after 20 hrs by AlphaLISA method	ic50	0.0011	uM
5-[(2S,6R)-11-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-methyl-4,7,10-triazatricyclo[7.4.0.02,7]trideca-1(9),10,12-trien-4-yl]-2-deuterioquinoline-8-carbonitrile	1777159: Inhibition of human TLR7 expressed in HEK293-Blue cells assessed as inhibition of R848-induced NF-kappaB/AP-1 activation measured after 20 hrs using quanti-blue as substrate by SEAP reporter gene based spectrophotometry assay	ic50	0.0013	uM
2-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-methyl-6-piperidin-4-yl-9H-carbazole	1768800: Inhibition of human TLR7 in HEK-Blue hTLR7 cells assessed as reduction in gardiquimod-activated NF-KappaB by SEAP reporter assay	ic50	0.0014	uM
1-[[2-methoxy-4-[(oxan-4-ylamino)methyl]phenyl]methyl]-7-N-[(2R)-pentan-2-yl]pyrazolo[4,5-d]pyrimidine-5,7-diamine	2006822: Agonist activity at human TLR7 in HEK-Blue hTLR7 cells incubated for 18 hrs by QUANTI-Blue reagent based SEAP reporter assay	ic50	0.0014	uM
1-[4-[7-(2,6-dimethyl-4-pyridinyl)-5-methyl-9H-carbazol-3-yl]piperidin-1-yl]-2-methylpropan-2-ol	1768800: Inhibition of human TLR7 in HEK-Blue hTLR7 cells assessed as reduction in gardiquimod-activated NF-KappaB by SEAP reporter assay	ic50	0.0015	uM
4-amino-1-[[6-[4-[2-(dimethylamino)ethyl]piperazin-1-yl]-3-pyridinyl]methyl]-6-(trifluoromethyl)-3H-imidazo[4,5-c]pyridin-2-one	622817: Agonist activity at TLR7	ec50	0.0015	uM
4-amino-1-[[6-[methyl(2-piperidin-1-ylethyl)amino]-3-pyridinyl]methyl]-6-(trifluoromethyl)-3H-imidazo[4,5-c]pyridin-2-one	622817: Agonist activity at TLR7	ec50	0.0016	uM
6-amino-9-[4-(azepan-1-yl)butyl]-2-butoxy-7H-purin-8-one	1949280: Agonist activity at TLR7 in human PBMC assessed as IFN-alpha production after 24 hrs by electrochemiluminescence assay	ec50	0.0016	uM
6-amino-2-butoxy-9-(6-piperidin-1-ylhexyl)-7H-purin-8-one	1949280: Agonist activity at TLR7 in human PBMC assessed as IFN-alpha production after 24 hrs by electrochemiluminescence assay	ec50	0.0016	uM
2-deuterio-5-[(2S,6R)-11-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-6-methyl-4,7,10-triazatricyclo[7.4.0.02,7]trideca-1(9),10,12-trien-4-yl]quinoline-8-carbonitrile	1777159: Inhibition of human TLR7 expressed in HEK293-Blue cells assessed as inhibition of R848-induced NF-kappaB/AP-1 activation measured after 20 hrs using quanti-blue as substrate by SEAP reporter gene based spectrophotometry assay	ic50	0.0017	uM
4-amino-1-[[6-[(2S)-2-(pyrrolidin-1-ylmethyl)pyrrolidin-1-yl]-3-pyridinyl]methyl]-6-(trifluoromethyl)-3H-imidazo[4,5-c]pyridin-2-one	622816: Agonist activity at TLR7 in human PBMC assessed as induction of type 1 interferon production	ec50	0.0017	uM
4-amino-1-[[6-(2-pyrrolidin-1-ylethylamino)-3-pyridinyl]methyl]-6-(trifluoromethyl)-3H-imidazo[4,5-c]pyridin-2-one	622817: Agonist activity at TLR7	ec50	0.0017	uM
2-(2-fluoro-6-methyl-4-pyridinyl)-5-piperidin-4-yl-3-propan-2-yl-1H-indole	1880294: Antagonist activity at gardiquimod stimulated human TRL7 overexpressed in HEK293 cells assessed as inhibition of NF kappa B/Ap-1 activation preincubated with compound for 30 mins followed by gardiquimod stimulation measured after 22 hrs by SEAP reporter assay	ic50	0.0018	uM
4-butyl-3-[[4-(methylaminomethyl)phenyl]methyl]-12-thia-3,5,8-triazatricyclo[7.3.0.02,6]dodeca-1(9),2(6),4,7,10-pentaen-7-amine	1970792: Agonist activity at human TLR7 expressed in HEK-Blue hTLR7 cells by reporter gene assay	ec50	0.0018	uM
2-(2-methoxy-6-methyl-4-pyridinyl)-5-piperidin-4-yl-3-propan-2-yl-1H-indole	1880294: Antagonist activity at gardiquimod stimulated human TRL7 overexpressed in HEK293 cells assessed as inhibition of NF kappa B/Ap-1 activation preincubated with compound for 30 mins followed by gardiquimod stimulation measured after 22 hrs by SEAP reporter assay	ic50	0.0019	uM

CTD chemical–gene interactions

37 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
resiquimod	affects binding, increases activity	2
gardiquimod	increases activity, increases expression, decreases reaction	2
Benzo(a)pyrene	increases methylation, affects methylation, decreases expression	2
SZU-101	affects binding, increases activity	1
AZD8848	increases activity	1
triphenyl phosphate	affects expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
lipopolysaccharide, E. coli O26-B6	increases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
N-(4-(4-amino-2-ethyl-1H-imidazo(4,5c)quinolin-1-yl)butyl)methanesulfonamide	increases activity	1
CL097 compound	affects binding, increases activity	1
Antigens, Viral	increases activity	1
Arsenic	increases expression	1
Cadmium	decreases expression, increases abundance	1
Chloroquine	decreases activity	1
Endosulfan	decreases expression	1
Hydroxychloroquine	decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment, decreases expression	1
Metformin	affects cotreatment, increases expression	1
Nickel	increases expression	1
Oligoribonucleotides	increases activity	1
Paraquat	affects cotreatment, decreases expression	1
Poly I-C	increases expression	1
Progesterone	increases expression	1
Zidovudine	affects cotreatment, increases expression	1
Mifepristone	decreases expression	1
Paclitaxel	affects cotreatment, increases expression	1
Gold Compounds	affects cotreatment, increases expression	1
Silver Compounds	increases expression	1

ChEMBL screening assays

356 unique, capped per target: 321 binding, 35 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1247821	Binding	Inhibition of TLR7/TLR9-mediated activation of aldrithiol-2-treated HIV1 Ada-stimulated human PBMC assessed as CD86 expressing cells at 100 uM after 20 hrs by flow cytometry	Chloroquine modulates HIV-1-induced plasmacytoid dendritic cell alpha interferon: implication for T-cell activation. — Antimicrob Agents Chemother
CHEMBL1023610	Functional	Agonist activity at human TLR7 expressed in HEK293XL cells assessed as NF-kappaB activation after 18 hrs	Synthetic oligoribonucleotides containing arabinonucleotides act as agonists of TLR7 and 8. — Bioorg Med Chem Lett

Cellosaurus cell lines

13 cell lines: 7 transformed cell line, 4 cancer cell line, 1 induced pluripotent stem cell, 1 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B8R1	Abcam HCT 116 TLR7 KO	Cancer cell line	Male
CVCL_B9TF	Abcam A-549 TLR7 KO	Cancer cell line	Male
CVCL_C7YS	HAP1 TLR7 (-)	Cancer cell line	Male
CVCL_D7A3	Leeporter HEK293 TLR7/NF-kB luciferase	Transformed cell line	Female
CVCL_E6V1	Genomeditech HEK-293 H_TLR7 Reporter	Transformed cell line	Female
CVCL_E8DA	HEK-Blue hTLR7 v2	Transformed cell line	Female
CVCL_E8FB	THP1-Dual hTLR7	Cancer cell line	Male
CVCL_IM84	HEK-Blue hTLR7	Transformed cell line	Female
CVCL_RQ76	HEK 293/TLR7/NF-kB Luciferase Reporter	Transformed cell line	Female
CVCL_WR14	KSCBi005-A-4	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00120887	PHASE4	COMPLETED	Lupus Atherosclerosis Prevention Study
NCT00125307	PHASE4	COMPLETED	Tacrolimus for the Treatment of Systemic Lupus Erythematosus With Membranous Nephritis
NCT00188188	PHASE4	UNKNOWN	Study of Endothelial Dysfunction in Systemic Lupus and Its Role in Heart Disease
NCT00371501	PHASE4	COMPLETED	Aspirin and Statins for Prevention of Atherosclerosis and Arterial Thromboembolism in Systemic Lupus Erythematosus
NCT00392093	PHASE4	COMPLETED	Effect of Hormone Replacement Therapy on Lupus Activity
NCT00413361	PHASE4	COMPLETED	The Reduction of Systemic Lupus Erythematosus Flares :Study PLUS
NCT00508898	PHASE4	WITHDRAWN	The Efficacy and Safety of Calcitriol for the Treatment of Lupus Nephritis and Persistent Proteinuria
NCT00668330	PHASE4	COMPLETED	Steroid Induced Osteoporosis in Patients With Systemic Lupus Erythematosus
NCT00739050	PHASE4	TERMINATED	Effect of Simvastatin on Endothelial Function in Premenopausal Women With Systemic Lupus Erythematosus (0733-271)(TERMINATED)
NCT00815282	PHASE4	COMPLETED	Immune Response After Human Papillomavirus Vaccination in Patients With Autoimmune Disease
NCT00828178	PHASE4	COMPLETED	Efficacy of Fish Oil in Lupus Patients
NCT00866229	PHASE4	UNKNOWN	Efficacy and Adverse Effect of Simvastatin Compare to Rosuvastatin in Systemic Lupus Erythematosus (SLE) Patients With Corticosteroid Therapy and High Low-Density Lipoprotein (LDL) Cholesterol Level
NCT00911521	PHASE4	COMPLETED	Immunogenicity and Safety of a Quadrivalent Human Papillomavirus (HPV) Vaccine in Patients With SLE: a Controlled Study
NCT01101802	PHASE4	COMPLETED	Mycophenolate Mofetil in Systemic Lupus Erythematosus (MISSILE)
NCT01112215	PHASE4	COMPLETED	Enteric-coated Mycophenolate Sodium Versus Azathioprine for the Extra-renal Lupus Manifestations
NCT01151644	PHASE4	UNKNOWN	Safety and Efficacy of Anti-Pandemic H1N1 Vaccination in Rheumatic Diseases
NCT01276782	PHASE4	WITHDRAWN	Levothyroxine in Pregnant SLE Patients
NCT01322308	PHASE4	COMPLETED	Effect of Pioglitazone on Endothelial Function in Premenopausal Women With Uncomplicated Systemic Lupus Erythematosus
NCT01359826	PHASE4	WITHDRAWN	The Effect of Milnacipran on Fatigue and Quality of Life in Lupus Patients
NCT01597492	PHASE4	COMPLETED	A Study to Evaluate the Effect of Belimumab on Vaccine Responses in Subjects With Systemic Lupus Erythematosus (SLE)
NCT01632241	PHASE4	COMPLETED	Efficacy and Safety of Belimumab in Black Race Patients With Systemic Lupus Erythematosus (SLE)
NCT01705977	PHASE4	COMPLETED	Belimumab Assessment of Safety in SLE
NCT01753401	PHASE4	COMPLETED	Acthar for the Treatment of Systemic Lupus Erythematosus (SLE) in Patients With a History of Persistently Active Disease
NCT02270970	PHASE4	UNKNOWN	Evaluation of Belimumab Impact on a BLyS Activity Signature Test in the Absence of Confounding Polypharmacy
NCT02477150	PHASE4	COMPLETED	Safety and Immunogenicity of a Zoster Vaccine in SLE
NCT02741960	PHASE4	COMPLETED	The Effect of Metformin on Reducing Lupus Flares
NCT02779153	PHASE4	WITHDRAWN	Acthar SLE (Systemic Lupus Erythematosus)
NCT02953821	PHASE4	COMPLETED	Acthar Gel for Active Systemic Lupus Erythematosus (SLE)
NCT03042260	PHASE4	UNKNOWN	Prophylactic Trimethoprim/Sulfamethoxazole to Prevent Severe Infections in Patients With Lupus Erythematous
NCT03098823	PHASE4	COMPLETED	A Crossover Study to Compare RAYOS to IR Prednisone to Improve Fatigue and Morning Symptoms for SLE
NCT03122431	PHASE4	COMPLETED	Relevance of Monitoring Blood and Salivar Levels of Drugs Used in Rheumatic Autoimmune Diseases
NCT03543839	PHASE4	RECRUITING	Trial of Belimumab in Early Lupus
NCT04447053	PHASE4	UNKNOWN	Sequential Belimumab and T-cell Based Therapy in SLE
NCT04515719	PHASE4	COMPLETED	Efficacy and Safety of Belimumab in SLE Patients
NCT04893161	PHASE4	UNKNOWN	A Model About the Response of Belimumab in SLE
NCT04908865	PHASE4	COMPLETED	Open-label Study of Belimumab Plus Standard Therapy in Chinese Pediatric Participants With Active Systemic Lupus Erythematosus (SLE)
NCT04956484	PHASE4	COMPLETED	Belimumab In Early Systemic Lupus Erythematosus
NCT05559671	PHASE4	RECRUITING	Safety of the Herpes Zoster Subunit Vaccine in Lupus
NCT05666336	PHASE4	UNKNOWN	Multi-omics Studies on the Efficacy of Telitacicept in Chinese SLE Patients
NCT05748925	PHASE4	COMPLETED	Cardio Renal Effects of SGLT2 Inhibitors Among Lupus Nephritis Patients