TLR1

Summary

TLR1 (toll like receptor 1, HGNC:11847) is a protein-coding gene on chromosome 4p14, encoding Toll-like receptor 1 (Q15399). Participates in the innate immune response to microbial agents.

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. 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. The various TLRs exhibit different patterns of expression. This gene is ubiquitously expressed, and at higher levels than other TLR genes. Different length transcripts presumably resulting from use of alternative polyadenylation site, and/or from alternative splicing, have been noted for this gene.

Source: NCBI Gene 7096 — RefSeq curated summary.

At a glance

• GWAS associations: 30
• Clinical variants (ClinVar): 152 total — 2 pathogenic
• Phenotypes (HPO): 1
• Druggable target: yes
• MANE Select transcript: NM_003263

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11847
Approved symbol	TLR1
Name	toll like receptor 1
Location	4p14
Locus type	gene with protein product
Status	Approved
Aliases	rsc786, KIAA0012, CD281
Ensembl gene	ENSG00000174125
Ensembl biotype	protein_coding
OMIM	601194
Entrez	7096

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 10 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000308979, ENST00000502213, ENST00000505744, ENST00000505940, ENST00000506146, ENST00000508364, ENST00000508535, ENST00000509754, ENST00000510552, ENST00000515861, ENST00000862584, ENST00000862585, ENST00000862586, ENST00000862587

RefSeq mRNA: 1 — MANE Select: NM_003263 NM_003263

CCDS: CCDS33973

Canonical transcript exons

ENST00000308979 — 4 exons

Exon	Start	End
ENSE00001208820	38796255	38798898
ENSE00001245734	38800857	38800948
ENSE00001245741	38804306	38804382
ENSE00004282108	38804754	38804791

Expression profiles

Bgee: expression breadth ubiquitous, 218 present calls, max score 96.75.

FANTOM5 (CAGE): breadth broad, TPM avg 7.9256 / max 912.5987, expressed in 676 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
51809	6.9161	587
51814	1.4257	413
51811	0.7430	233
51810	0.2147	80
51815	0.1401	50
51812	0.0518	25

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	96.75	gold quality
mononuclear cell	CL:0000842	96.30	gold quality
leukocyte	CL:0000738	96.10	gold quality
blood	UBERON:0000178	94.71	gold quality
bone marrow cell	CL:0002092	90.87	gold quality
bone marrow	UBERON:0002371	89.66	gold quality
calcaneal tendon	UBERON:0003701	89.06	gold quality
granulocyte	CL:0000094	88.99	gold quality
vermiform appendix	UBERON:0001154	88.14	gold quality
gall bladder	UBERON:0002110	85.28	gold quality
spleen	UBERON:0002106	85.12	gold quality
lymph node	UBERON:0000029	83.19	gold quality
periodontal ligament	UBERON:0008266	82.83	gold quality
rectum	UBERON:0001052	81.57	gold quality
right lung	UBERON:0002167	81.21	gold quality
caecum	UBERON:0001153	79.88	gold quality
smooth muscle tissue	UBERON:0001135	79.42	gold quality
palpebral conjunctiva	UBERON:0001812	79.30	gold quality
tonsil	UBERON:0002372	79.06	gold quality
colonic epithelium	UBERON:0000397	78.70	gold quality
epithelium of nasopharynx	UBERON:0001951	78.57	gold quality
nasopharynx	UBERON:0001728	78.55	gold quality
right coronary artery	UBERON:0001625	78.41	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	78.31	gold quality
upper lobe of left lung	UBERON:0008952	77.67	gold quality
minor salivary gland	UBERON:0001830	77.07	gold quality
islet of Langerhans	UBERON:0000006	76.74	gold quality
upper lobe of lung	UBERON:0008948	76.44	gold quality
body of pancreas	UBERON:0001150	76.20	gold quality
descending thoracic aorta	UBERON:0002345	76.04	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.87

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF2, JUN, JUND

miRNA regulators (miRDB)

26 targeting TLR1, 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-548AW	99.99	72.57	3559
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-3973	99.20	69.19	1990
HSA-MIR-140-3P	99.04	67.69	1324
HSA-MIR-520G-3P	98.91	67.38	1914
HSA-MIR-520H	98.91	67.38	1914
HSA-MIR-616-3P	96.82	66.99	784
HSA-MIR-597-5P	96.82	67.57	732

Literature-anchored findings (GeneRIF, showing 40)

• The extracellular, but not cytoplasmic domain of TLR1 inhibits Toll-like receptor 4 signaling in endothelial cells. TLR1 might restrain the dangerous innate response to LPS by binding to TLR4 and preventing the formation of active signaling complexes. (PMID:11932926)
• These data indicate that TLR1 and TLR2 are required for lipoprotein recognition and hat defects in the TLR1/2 signaling pathway may account for human hyporesponsiveness to Borrelia burgdorferi OspA vaccination. (PMID:12091878)
• All nine patients expressed all of the TLRs studied, whereas only five out of the nine patients had any granulomas positive for IL-4.The associations between TLRs 1, 5, and 9 were different in IL-4-negative compared with IL-4-positive patients. (PMID:12600829)
• TLR1 and TLR2 are required for ara-lipoarabinomannan- and tripalmitoyl cysteinyl lipopeptide-stimulated cytokine secretion from mononuclear cells. Confocal microscopy revealed that TLR1 and TLR2 cotranslationally form heterodimeric complexes (PMID:12975352)
• Toll-like receptor 2 dimerized with Toll-like receptor 6 or 1 is activated by saturated fatty acid and inhibited by polyunsaturated fatty acid (PMID:14966134)
• The surface expression of TLR1 by FACS analysis after the stimulation of JAR cells with different TLR ligands. (PMID:15790341)
• TLR2-TLR1 coactivation serves as the underlying mechanism for the proinflammatory toxicities associated with Amphotericin B (PMID:15793154)
• The observed multiple associated SNPs at the TLR6-TLR1-TLR10 gene cluster were dependent and suggest the presence of a founder prostate cancer risk variant on this haplotype background. (PMID:15812078)
• Diminished expression and function of TLR1 is a likely consequence of chronic filarial antigen stimulation and could serve as a novel mechanism underlying the dysfunctional immune response in lymphatic filariasis (PMID:16002719)
• Reduced signaling via TLR-2/TLR-1 heterodimers protects from late stage Lyme disease in individuals with heterozygous Arg753Gln polymorphism of Tlr-2 (PMID:16081826)
• Activation of NF-kappa B in monocytic THP-1 cells by a lipid-associated membrane protein (LAMP) from Mycoplasma pneumoniae is mediated by TLR2. (PMID:16177110)
• Toll-Like Receptor 2 (TLR2) recognizes PorB through direct binding, and that PorB-induced cell activation is mediated by a TLR2/TLR1 complex (PMID:16455995)
• Presence of TLR1 239G > C (Arg80 > Thr) or the presence of both TLR1 743A > G (Asn248 > Ser) and TLR6 745C > T (Ser249 > Pro) single nucleotide polymorphism is associated with invasive aspergillosis following allogeneic stem cell transplantation. (PMID:16461792)
• This study suggests that CD14 directly binds to triacylated lipopeptides and facilitates recognition of the lipopeptides by the TLR2/TLR1 complex without binding to the receptor complex. (PMID:16848791)
• TLR-2/6 and TLR2/1 heterodimer sorting at the cell surface determines heterotypic associations with CD36 and intracellular targeting (PMID:16880211)
• In vitro functional studies involving TLR1 Gly676Ala and TLR1 Gly676Leu results in reduced NF-kappa B activation of signal-deficient mutants. (PMID:16893894)
• These data suggest that Toll-like receptor 2 and 4 expression correlates with the extent and severity of coronary artery disease. (PMID:17172927)
• Diminished TLR1/2 signaling may contribute to the increased infection-related morbidity and mortality and the impaired vaccine responses observed in aging humans (PMID:17202359)
• Intestinal enteroendocrine cells express TLRs which may be involved in innate immune responses. (PMID:17395901)
• TLR1 single nucleotide polymorphism P315L may predispose certain individuals to infectious diseases for which the sensing of microbial cell components by TLR1 is critical to innate immune defense. (PMID:17475868)
• We report that I602S, a common single nucleotide polymorphism within TLR1, is associated with aberrant trafficking of the receptor to the cell surface and diminished responses of blood monocytes to bacterial agonists. (PMID:17548585)
• variation in the inflammatory response to bacterial lipopeptides is regulated by a common TLR1 transmembrane domain polymorphism (PMID:17595679)
• Propose that formation of the TLR1-TLR2 heterodimer brings the intracellular TIR domains close to each other to promote dimerization and initiate signaling. (PMID:17889651)
• We genotyped 19 common (>5%) haplotype-tagging SNPs chosen from the SNPs discovered in a resequencing study spanning TLR6, TLR1, and TLR10 to test for the association between sequence variants cluster and prostate cancer. (PMID:17932345)
• activation of NF-kappaB by beta-defensin 3 depends on the expression of both TLR1 and TLR2 (PMID:18006661)
• Heterodimerization of TLR2 with TLR1 or TLR6 evolutionarily has developed to expand the ligand spectrum to enable the innate immune system to recognize the numerous, different structures of various bacterial lipopolysaccharides. (PMID:18056480)
• TLR1, 2, and 4 protein colocalized with adiponectin in human adipocytes. (PMID:18292749)
• The lipoproteins from U. parvum were found to activate NF-kappaB through TLR1, TLR2 and TLR6. (PMID:18451040)
• Findings suggest that TLR1 deficiency influences adaptive immunity during leprosy infection to affect clinical manifestations such as nerve damage and disability. (PMID:18461142)
• the results show that MG149, a triacylated lipoprotein from M. genitalium, activates NF-kappaB through TLR1 and TLR2. (PMID:18474641)
• These results suggest that functional relevant TLR1 and TLR6 variants are directly involved in asthma development. (PMID:18547625)
• Hypermorphic genetic variation in TLR1 (toll-like receptor 1) is associated with increased susceptibility to organ dysfunction, death, and gram-positive infection in sepsis. (PMID:18635889)
• Through cooperation of TLR1 and TLR2 signaling, TLR5 is stored intracellularly in neutrophils and is up-regulated in a protein synthesis-independent manner. (PMID:18684966)
• 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)
• common haplotype in the TLR10-TLR1-TLR6 gene cluster influences prostate cancer risk and clearly supports the need for further investigation of TLR genes in other populations (PMID:18752252)
• Altered TLR1 function, or at least a TLR1 N248S-linked trait, may affect the progression from leprosy infection to disease as well as the disease course and the risk of debilitating reactional episodes. (PMID:19456232)
• the IL-1beta and VDR activation pathways have roles in human TLR2/1-induced antimicrobial responses (PMID:19503839)
• polymorphisms in TLRs 1, 4, and 5 are associated with altered risks of urinary tract infections in adult women (PMID:19543401)
• Studies provide molecular model for TLR and NLR signalling pathways. (PMID:19818630)
• Studies show substantial decreases in older compared with young individuals in cytokine production in response to TLR1/2, TLR6, TLR3, TLR5, and TLR8, TLR7 and TLR9 in DCs. (PMID:20100933)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tlr1	ENSMUSG00000044827
rattus_norvegicus	Tlr1	ENSRNOG00000038722

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), TLR6 (ENSG00000174130), LRRC3B (ENSG00000179796), TSKU (ENSG00000182704), TLR5 (ENSG00000187554), TLR7 (ENSG00000196664), LRIT2 (ENSG00000204033), LRRC3C (ENSG00000204913)

Protein

Protein identifiers

Toll-like receptor 1 — Q15399 (reviewed: Q15399)

Alternative names: Toll/interleukin-1 receptor-like protein

All UniProt accessions (5): Q15399, D6RA99, D6RAP2, D6RCE8, D6RF68

UniProt curated annotations — full annotation on UniProt →

Function. Participates in the innate immune response to microbial agents. Specifically recognizes diacylated and triacylated lipopeptides. Cooperates with TLR2 to mediate the innate immune response to bacterial lipoproteins or lipopeptides. Forms the activation cluster TLR2:TLR1:CD14 in response to triacylated lipopeptides, this cluster triggers signaling from the cell surface and subsequently is targeted to the Golgi in a lipid-raft dependent pathway. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response.

Subunit / interactions. Interacts (via extracellular domain) with TLR2. TLR2 seems to exist in heterodimers with either TLR1 or TLR6 before stimulation by the ligand. The heterodimers form bigger oligomers in response to their corresponding ligands as well as further heterotypic associations with other receptors such as CD14 and/or CD36. The activation cluster TLR2:TLR1:CD14 forms in response to triacylated lipopeptides. Binds MYD88 (via TIR domain). Interacts with CNPY3. Interacts with neutrophil recruitment protein from Aedes aegypti saliva; the interaction probably promotes activation of canonical NF-kappa-B signaling in skin-resident macrophages and subsequent expression of neutrophil chemoattractants.

Subcellular location. Cell membrane. Cytoplasmic vesicle. Phagosome membrane. Membrane raft. Golgi apparatus.

Tissue specificity. Ubiquitous. Highly expressed in spleen, ovary, peripheral blood leukocytes, thymus and small intestine.

Polymorphism. Genetic variations in TLR1 may influence susceptibility to or protection against contracting leprosy and define the leprosy susceptibility locus 5 [MIM:613223]. Ser-602 is a common allele in Caucasians. It is associated with impaired cell surface expression and receptor function resulting in protection against leprosy.

Similarity. Belongs to the Toll-like receptor family.

RefSeq proteins (1): NP_003254* (*=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
IPR017241	Toll-like_receptor	Family
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR035897	Toll_tir_struct_dom_sf	Homologous_superfamily

Pfam: PF01463, PF01582, PF13855

UniProt features (122 total): strand 30, helix 26, repeat 19, sequence variant 18, turn 8, glycosylation site 6, disulfide bond 4, sequence conflict 3, topological domain 2, domain 2, signal peptide 1, chain 1, region of interest 1, transmembrane region 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
7NUW	X-RAY DIFFRACTION	1.9
2Z7X	X-RAY DIFFRACTION	2.1
6NIH	X-RAY DIFFRACTION	2.3
7NUX	X-RAY DIFFRACTION	2.47
1FYV	X-RAY DIFFRACTION	2.9
7NT7	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15399-F1	87.03	0.54

Functional residue map

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

Disulfide bonds (4): 110–132, 223–230, 343–368, 419–442

Glycosylation sites (6): 51, 137, 163, 330, 429, 578

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-1236974	ER-Phagosome pathway
R-HSA-1461957	Beta defensins
R-HSA-166058	MyD88:MAL(TIRAP) cascade initiated on plasma membrane
R-HSA-168179	Toll Like Receptor TLR1:TLR2 Cascade
R-HSA-5602498	MyD88 deficiency (TLR2/4)
R-HSA-5603041	IRAK4 deficiency (TLR2/4)
R-HSA-5686938	Regulation of TLR by endogenous ligand
R-HSA-9705671	SARS-CoV-2 activates/modulates innate and adaptive immune responses

MSigDB gene sets: 387 (showing top): DAVIES_MULTIPLE_MYELOMA_VS_MGUS_DN, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_POSITIVE_REGULATION_OF_INTERLEUKIN_8_PRODUCTION, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, MODULE_45, MODULE_64, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_DETECTION_OF_OTHER_ORGANISM, GOBP_POSITIVE_REGULATION_OF_TUMOR_NECROSIS_FACTOR_SUPERFAMILY_CYTOKINE_PRODUCTION, GOBP_TOLL_LIKE_RECEPTOR_SIGNALING_PATHWAY

GO Biological Process (16): microglial cell activation (GO:0001774), toll-like receptor signaling pathway (GO:0002224), inflammatory response (GO:0006954), immune response (GO:0006955), signal transduction (GO:0007165), positive regulation of interleukin-6 production (GO:0032755), positive regulation of interleukin-8 production (GO:0032757), positive regulation of tumor necrosis factor production (GO:0032760), positive regulation of toll-like receptor 2 signaling pathway (GO:0034137), macrophage activation (GO:0042116), detection of triacyl bacterial lipopeptide (GO:0042495), innate immune response (GO:0045087), cellular response to triacyl bacterial lipopeptide (GO:0071727), immune system process (GO:0002376), defense response (GO:0006952), response to bacterial lipoprotein (GO:0032493)

GO Molecular Function (7): transmembrane signaling receptor activity (GO:0004888), Toll-like receptor 2 binding (GO:0035663), signaling receptor activity (GO:0038023), identical protein binding (GO:0042802), lipopeptide binding (GO:0071723), protein binding (GO:0005515), NAD+ nucleosidase activity, cyclic ADP-ribose generating (GO:0061809)

GO Cellular Component (8): Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), membrane (GO:0016020), phagocytic vesicle membrane (GO:0030670), Toll-like receptor 1-Toll-like receptor 2 protein complex (GO:0035354), signaling receptor complex (GO:0043235), membrane raft (GO:0045121), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Diseases associated with the TLR signaling cascade	2
Antigen processing-Cross presentation	1
Defensins	1
Toll Like Receptor 4 (TLR4) Cascade	1
Toll Like Receptor TLR1:TLR2 Cascade	1
Toll Like Receptor TLR6:TLR2 Cascade	1
Toll Like Receptor 2 (TLR2) Cascade	1
Toll-like Receptor Cascades	1
SARS-CoV-2-host interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of cytokine production	2
response to triacyl bacterial lipopeptide	2
cytoplasm	2
leukocyte activation involved in inflammatory response	1
macrophage activation	1
glial cell activation	1
pattern recognition receptor signaling pathway	1
defense response	1
immune system process	1
response to stimulus	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
interleukin-6 production	1
regulation of interleukin-6 production	1
interleukin-8 production	1
regulation of interleukin-8 production	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
positive regulation of tumor necrosis factor superfamily cytokine production	1
toll-like receptor 2 signaling pathway	1
regulation of toll-like receptor 2 signaling pathway	1
positive regulation of pattern recognition receptor signaling pathway	1
myeloid leukocyte activation	1
detection of bacterial lipopeptide	1
immune response	1
defense response to symbiont	1
cellular response to bacterial lipopeptide	1
biological_process	1
response to stress	1
response to molecule of bacterial origin	1
signaling receptor activity	1
Toll-like receptor binding	1
molecular transducer activity	1
protein binding	1
lipid binding	1
binding	1
hydrolase activity, hydrolyzing N-glycosyl compounds	1

Protein interactions and networks

STRING

3024 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TLR1	TIRAP	P58753	992
TLR1	MYD88	P78397	988
TLR1	TLR2	O60603	986
TLR1	TLR4	O00206	986
TLR1	TLR6	Q9Y2C9	982
TLR1	TLR10	Q9BXR5	978
TLR1	SCARB1	Q8WTV0	941
TLR1	SCARB2	Q14108	931
TLR1	CD36	P16671	930
TLR1	IL6	P05231	884
TLR1	LY96	Q9Y6Y9	883
TLR1	IRAK4	Q9NWZ3	853
TLR1	TLR5	O60602	828
TLR1	IL1B	P01584	807
TLR1	TNF	P01375	804

IntAct

16 interactions, top by confidence:

A	B	Type	Score
TLR1	TLR10	psi-mi:“MI:0915”(physical association)	0.570
TLR1	TLR6	psi-mi:“MI:0915”(physical association)	0.550
TLR6	TLR1	psi-mi:“MI:0915”(physical association)	0.550
TLR1	TLR1	psi-mi:“MI:0915”(physical association)	0.510
TLR1	TLR2	psi-mi:“MI:0915”(physical association)	0.510
TLR2	TLR1	psi-mi:“MI:0915”(physical association)	0.510
SIGLEC5	TLR1	psi-mi:“MI:0915”(physical association)	0.400
SIGLEC9	TLR1	psi-mi:“MI:0915”(physical association)	0.400
SIGLEC10	TLR1	psi-mi:“MI:0915”(physical association)	0.400
TLR1	LRP6	psi-mi:“MI:0914”(association)	0.350

BioGRID (31): TLR1 (Far Western), TLR1 (Far Western), TLR6 (Affinity Capture-MS), ALDH16A1 (Affinity Capture-MS), DERA (Affinity Capture-MS), CNPY3 (Affinity Capture-MS), TBC1D24 (Affinity Capture-MS), TMEM214 (Affinity Capture-MS), PLXNB2 (Affinity Capture-MS), MAVS (Affinity Capture-MS), TLR2 (Affinity Capture-Western), TLR1 (Affinity Capture-Western), STK11IP (Affinity Capture-MS), TLR1 (Affinity Capture-Western), LRP6 (Affinity Capture-MS)

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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	108
Likely benign	20
Benign	11

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
983492	NM_003263.4(TLR1):c.2036T>C (p.Ile679Thr)	Pathogenic
983493	NM_003263.4(TLR1):c.1324T>C (p.Cys442Arg)	Pathogenic

SpliceAI

935 predictions. Top by Δscore:

Variant	Effect	Δscore
4:38804749:CTTA:C	donor_loss	0.9800
4:38804752:A:AC	donor_gain	0.9800
4:38804752:A:C	donor_loss	0.9800
4:38804753:C:CC	donor_gain	0.9800
4:38856511:T:TA	donor_gain	0.9800
4:38856520:A:AC	donor_gain	0.9800
4:38798899:C:CC	acceptor_gain	0.9700
4:38856759:A:AC	donor_gain	0.9700
4:38856760:C:CC	donor_gain	0.9700
4:38844268:C:CT	acceptor_gain	0.9600
4:38844265:A:C	acceptor_gain	0.9500
4:38856755:ACT:A	donor_loss	0.9500
4:38856757:TTAC:T	donor_loss	0.9500
4:38856758:T:TC	donor_loss	0.9500
4:38800855:AC:A	donor_gain	0.9400
4:38800856:CC:C	donor_gain	0.9400
4:38800947:CC:C	acceptor_gain	0.9300
4:38800948:CC:C	acceptor_gain	0.9300
4:38804383:C:CC	acceptor_gain	0.9300
4:38844263:T:C	acceptor_gain	0.9300
4:38798897:TT:T	acceptor_gain	0.9200
4:38804760:A:AT	donor_gain	0.9200
4:38829538:C:CC	acceptor_gain	0.9200
4:38856758:TA:T	donor_gain	0.9200
4:38803032:C:T	acceptor_gain	0.9100
4:38844263:T:TC	acceptor_gain	0.9100
4:38856757:TTA:T	donor_gain	0.9100
4:38856759:A:C	donor_gain	0.9100
4:38829536:TT:T	acceptor_gain	0.9000
4:38856752:TCTAC:T	donor_gain	0.9000

AlphaMissense

5267 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:38796912:A:C	F640L	0.993
4:38796912:A:T	F640L	0.993
4:38796914:A:G	F640L	0.993
4:38796745:A:T	V696D	0.992
4:38796813:A:C	F673L	0.991
4:38796813:A:T	F673L	0.991
4:38796815:A:G	F673L	0.991
4:38796560:A:G	W758R	0.990
4:38796560:A:T	W758R	0.990
4:38796729:A:C	F701L	0.990
4:38796729:A:T	F701L	0.990
4:38796731:A:G	F701L	0.990
4:38796716:A:G	W706R	0.988
4:38796716:A:T	W706R	0.988
4:38797569:C:A	W421C	0.988
4:38797569:C:G	W421C	0.988
4:38796742:A:G	L697S	0.984
4:38796762:A:C	S690R	0.984
4:38796762:A:T	S690R	0.984
4:38796764:T:G	S690R	0.984
4:38796786:A:C	N682K	0.984
4:38796786:A:T	N682K	0.984
4:38796528:A:C	F768L	0.983
4:38796528:A:T	F768L	0.983
4:38796530:A:G	F768L	0.983
4:38796884:A:G	W650R	0.983
4:38796884:A:T	W650R	0.983
4:38796558:C:A	W758C	0.982
4:38796558:C:G	W758C	0.982
4:38796714:C:A	W706C	0.982

dbSNP variants (sampled 300 via entrez): RS1000298484 (4:38805870 A>C,G), RS1000325195 (4:38787460 AAAAAAAAAAAAAG>A), RS1000394289 (4:38805484 A>G), RS10005625 (4:38793531 C>T), RS1000663448 (4:38806912 T>C), RS1000980976 (4:38798263 T>C), RS1001014765 (4:38787231 G>A), RS1001231932 (4:38806638 T>A,C), RS1001258464 (4:38793816 G>A,T), RS1001285055 (4:38807497 G>A,C,T), RS1001338522 (4:38801249 T>C), RS1001750914 (4:38803022 T>A,C), RS1002135181 (4:38807085 G>A,C), RS1002140529 (4:38790900 C>G,T), RS1002279830 (4:38806469 G>A,T)

Disease associations

OMIM: gene MIM:601194 | disease phenotypes: MIM:609888, MIM:613223, MIM:180300

GenCC curated gene-disease

Mondo (3): leprosy, susceptibility to, 1 (MONDO:0012358), leprosy, susceptibility to, 5 (MONDO:0013185), rheumatoid arthritis (MONDO:0008383)

Orphanet (2): Leprosy (Orphanet:548), NON RARE IN EUROPE: Rheumatoid arthritis (Orphanet:284130)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0001370	Rheumatoid arthritis

GWAS associations

30 associations (top):

Study	Trait	p-value
GCST002014_1	Helicobacter pylori serologic status	1.000000e-18
GCST002065_16	Alcohol consumption	3.000000e-06
GCST002083_15	Self-reported allergy	5.000000e-21
GCST002084_3	Allergic sensitization	5.000000e-11
GCST002322_2	Asthma and hay fever	5.000000e-12
GCST003797_3	Diabetes in response to antihypertensive drug treatment (treatment strategy interaction)	1.000000e-07
GCST003987_16	Asthma	4.000000e-11
GCST003990_4	Allergy	1.000000e-15
GCST005038_37	Allergic disease (asthma, hay fever or eczema)	3.000000e-58
GCST005174_11	Coronary artery calcified atherosclerotic plaque score in type 2 diabetes	4.000000e-06
GCST005332_2	Systemic sclerosis (anti-topoisomerase-positive)	2.000000e-06
GCST006408_2	Allergic sensitization	2.000000e-13
GCST006409_35	Allergic rhinitis	4.000000e-27
GCST007563_4	Allergic disease (asthma, hay fever or eczema)	7.000000e-20
GCST007564_38	Asthma or allergic disease (pleiotropy)	2.000000e-19
GCST007797_8	Asthma onset (childhood vs adult)	3.000000e-21
GCST007798_63	Asthma	2.000000e-31
GCST007800_40	Asthma (childhood onset)	3.000000e-74
GCST007994_24	Asthma (age of onset)	5.000000e-22
GCST007995_17	Asthma (childhood onset)	3.000000e-32
GCST008574_1	Composite immunoglobulin trait (IgG/IgM)	4.000000e-09
GCST008916_41	Asthma	3.000000e-10
GCST009719_5	Allergic rhinitis	2.000000e-25
GCST009720_98	Asthma	4.000000e-24
GCST009798_22	Asthma	4.000000e-17
GCST010042_130	Asthma	7.000000e-43
GCST010043_121	Asthma	4.000000e-42
GCST010984_11	Allergic disease (asthma, hay fever and/or eczema) (multivariate analysis)	3.000000e-38
GCST010985_27	Allergic disease (asthma, hay fever and/or eczema) (age of onset)	3.000000e-38
GCST90014325_17	Asthma	3.000000e-17

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004329	alcohol drinking
EFO:0005298	allergic sensitization measurement
EFO:0005405	response to antihypertensive drug
EFO:0007766	response to beta blocker
EFO:0007767	response to calcium channel blocker
EFO:0004723	coronary artery calcification
EFO:0008537	anti-topoisomerase-I-antibody-positive systemic scleroderma
EFO:0004847	age at onset

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D001172	Arthritis, Rheumatoid	C05.550.114.154; C05.799.114; C17.300.775.099; C20.111.199

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3714412 (SINGLE PROTEIN), CHEMBL3885643 (PROTEIN COMPLEX)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: catalytic receptor — Toll-like receptor family

ChEMBL bioactivities

194 potent at pChembl≥5 of 198 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.40	EC50	0.04	nM	CHEMBL5179849
10.30	EC50	0.05	nM	CHEMBL5202312
10.30	EC50	0.05	nM	CHEMBL5195088
10.22	EC50	0.06	nM	CHEMBL5208283
10.15	EC50	0.07	nM	CHEMBL5205616
10.15	EC50	0.07	nM	CHEMBL5179644
10.10	EC50	0.08	nM	CHEMBL5279981
10.00	EC50	0.1	nM	CHEMBL5185917
10.00	EC50	0.1	nM	CHEMBL5187007
10.00	EC50	0.1	nM	CHEMBL5194188
10.00	EC50	0.1	nM	CHEMBL5169846
10.00	EC50	0.1	nM	CHEMBL5192641
10.00	EC50	0.1	nM	CHEMBL5273912
10.00	EC50	0.1	nM	CHEMBL5267649
9.96	EC50	0.11	nM	CHEMBL4472879
9.89	EC50	0.13	nM	CHEMBL5265998
9.85	EC50	0.14	nM	CHEMBL5203424
9.85	EC50	0.14	nM	CHEMBL5181631
9.82	EC50	0.15	nM	CHEMBL5201759
9.82	EC50	0.15	nM	CHEMBL5197238
9.77	EC50	0.17	nM	CHEMBL5186180
9.77	EC50	0.17	nM	CHEMBL5276021
9.74	EC50	0.18	nM	CHEMBL5172228
9.74	EC50	0.18	nM	CHEMBL5275357
9.70	EC50	0.2	nM	CHEMBL5190772
9.70	EC50	0.2	nM	CHEMBL5196750
9.70	EC50	0.2	nM	CHEMBL5196411
9.70	EC50	0.2	nM	CHEMBL5284136
9.68	EC50	0.21	nM	CHEMBL5199615
9.68	EC50	0.21	nM	CHEMBL5188254
9.64	EC50	0.23	nM	CHEMBL5193367
9.60	EC50	0.25	nM	CHEMBL5169343
9.60	EC50	0.25	nM	CHEMBL5183964
9.60	EC50	0.25	nM	CHEMBL5191001
9.60	EC50	0.25	nM	CHEMBL5191057
9.60	EC50	0.25	nM	CHEMBL5282814
9.59	EC50	0.26	nM	CHEMBL5184916
9.59	EC50	0.26	nM	CHEMBL5198565
9.57	EC50	0.27	nM	CHEMBL5180856
9.55	EC50	0.28	nM	CHEMBL5269670
9.54	EC50	0.29	nM	CHEMBL5208333
9.52	EC50	0.3	nM	CHEMBL5205549
9.49	EC50	0.32	nM	CHEMBL5205005
9.48	EC50	0.33	nM	CHEMBL5196512
9.48	EC50	0.33	nM	CHEMBL5194475
9.48	EC50	0.33	nM	CHEMBL5281226
9.43	EC50	0.37	nM	CHEMBL5176430
9.42	EC50	0.38	nM	CHEMBL5193298
9.30	EC50	0.5	nM	CHEMBL5172955
9.30	EC50	0.5	nM	CHEMBL5207112

PubChem BioAssay actives

179 with measured affinity, of 449 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
(3S,4S)-1-[4-[(3S,4S)-3,4-bis[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]-3-N-[(1S,2R)-2-phenylcyclopropyl]-4-N-tetradec-13-ynylpyrrolidine-3,4-dicarboxamide	1893014: Agonist activity at TLR1/TLR2 in human THP-1 derived macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay	ec50	<0.0001	uM
(3S,4S)-1-[4-[(3S,4S)-3,4-bis[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]-3-N,4-N-bis[(1S,2R)-2-phenylcyclopropyl]pyrrolidine-3,4-dicarboxamide	1549436: Agonist activity at TLR1/2 in human THP-1 cells assessed as increase in TNF-alpha release incubated for 4 hrs by ELISA	ec50	0.0001	uM
12-[[(3S,4S)-1-[4-[(3S,4S)-3,4-bis[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]-4-[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-3-carbonyl]amino]dodecyl 2-[(2-methylpropan-2-yl)oxycarbonylamino]acetate	1893014: Agonist activity at TLR1/TLR2 in human THP-1 derived macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay	ec50	0.0001	uM
(3S,4S)-1-[4-[(3S,4S)-3,4-bis[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]-4-N-dodecyl-3-N-[(1S,2R)-2-phenylcyclopropyl]pyrrolidine-3,4-dicarboxamide	1893014: Agonist activity at TLR1/TLR2 in human THP-1 derived macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay	ec50	0.0001	uM
12-[[(3S,4S)-1-[4-[(3S,4S)-3,4-bis[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]-4-[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-3-carbonyl]amino]dodecyl 2-aminoacetate	1893014: Agonist activity at TLR1/TLR2 in human THP-1 derived macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay	ec50	0.0001	uM
12-[[(3S,4S)-1-[4-[(3S,4S)-3,4-bis[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]-4-[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-3-carbonyl]amino]dodecyl 2-(phenylmethoxycarbonylamino)acetate	1893014: Agonist activity at TLR1/TLR2 in human THP-1 derived macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay	ec50	0.0001	uM
12-[[(3S,4S)-1-[4-[(3S,4S)-3,4-bis[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]-4-[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-3-carbonyl]amino]dodecyl 2-acetamidoacetate	1893014: Agonist activity at TLR1/TLR2 in human THP-1 derived macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay	ec50	0.0001	uM
12-[[(3S,4S)-1-[4-[(3S,4S)-3,4-bis[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]-4-[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-3-carbonyl]amino]dodecyl (2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylmethoxypropanoate	1893014: Agonist activity at TLR1/TLR2 in human THP-1 derived macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay	ec50	0.0001	uM
(3S,4S)-1-[4-[(3S,4S)-3,4-bis[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]-4-N-decyl-3-N-[(1S,2R)-2-phenylcyclopropyl]pyrrolidine-3,4-dicarboxamide	1893014: Agonist activity at TLR1/TLR2 in human THP-1 derived macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay	ec50	0.0001	uM
12-[[(3S,4S)-1-[4-[(3S,4S)-3,4-bis[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]-4-[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-3-carbonyl]amino]dodecyl 4-aminobenzoate	1893014: Agonist activity at TLR1/TLR2 in human THP-1 derived macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay	ec50	0.0001	uM
(3S,4S)-1-[4-[(3S,4S)-3,4-bis[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]-3-N-[(1S,2R)-2-phenylcyclopropyl]-4-N-tetradecylpyrrolidine-3,4-dicarboxamide	1893014: Agonist activity at TLR1/TLR2 in human THP-1 derived macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay	ec50	0.0001	uM
(3S,4S)-1-[4-[(3S,4S)-3,4-bis[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]-4-N-[8-(4-hydroxyphenyl)octyl]-3-N-[(1S,2R)-2-phenylcyclopropyl]pyrrolidine-3,4-dicarboxamide	1893014: Agonist activity at TLR1/TLR2 in human THP-1 derived macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay	ec50	0.0001	uM
12-[[(3S,4S)-1-[4-[(3S,4S)-3,4-bis[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]-4-[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-3-carbonyl]amino]dodecyl 2-(dimethylamino)acetate	1893014: Agonist activity at TLR1/TLR2 in human THP-1 derived macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay	ec50	0.0001	uM
12-[[(3S,4S)-1-[4-[(3S,4S)-3,4-bis[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]-4-[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-3-carbonyl]amino]dodecyl acetate	1893014: Agonist activity at TLR1/TLR2 in human THP-1 derived macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay	ec50	0.0001	uM
12-[[(3S,4S)-1-[4-[(3S,4S)-3,4-bis[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]-4-[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-3-carbonyl]amino]dodecyl 2-phenylmethoxyacetate	1893014: Agonist activity at TLR1/TLR2 in human THP-1 derived macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay	ec50	0.0001	uM
(3S,4S)-4-N-(12-azidododecyl)-1-[4-[(3S,4S)-3,4-bis[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]-3-N-[(1S,2R)-2-phenylcyclopropyl]pyrrolidine-3,4-dicarboxamide	1893014: Agonist activity at TLR1/TLR2 in human THP-1 derived macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay	ec50	0.0001	uM
(3S,4S)-3-N,4-N-bis[(1S,2R)-2-(4-fluorophenyl)cyclopropyl]-1-[4-[(3S,4S)-4-[[(1S,2R)-2-(4-fluorophenyl)cyclopropyl]carbamoyl]-3-[[(1R,2S)-2-(4-fluorophenyl)cyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]pyrrolidine-3,4-dicarboxamide	1923425: Agonist activity at TLR2/TLR1 in human THP-1 cells	ec50	0.0001	uM
(3S,4S)-4-N-dodecyl-3-N-[(1S,2R)-2-phenylcyclopropyl]-1-[4-[(3S,4S)-4-[[(1R,2S)-2-phenylcyclopropyl]carbamoyl]-3-[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]pyrrolidine-3,4-dicarboxamide	1923425: Agonist activity at TLR2/TLR1 in human THP-1 cells	ec50	0.0001	uM
(3S,4S)-3-N-[(1S,2R)-2-phenylcyclopropyl]-1-[4-[(3S,4S)-4-[[(1R,2S)-2-phenylcyclopropyl]carbamoyl]-3-[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]-4-N-tetradecylpyrrolidine-3,4-dicarboxamide	1923425: Agonist activity at TLR2/TLR1 in human THP-1 cells	ec50	0.0001	uM
(3S,4S)-4-N-decyl-3-N-[(1S,2R)-2-phenylcyclopropyl]-1-[4-[(3S,4S)-4-[[(1R,2S)-2-phenylcyclopropyl]carbamoyl]-3-[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]pyrrolidine-3,4-dicarboxamide	1923425: Agonist activity at TLR2/TLR1 in human THP-1 cells	ec50	0.0001	uM
(3S,4S)-1-[(2E,4E)-6-[(3S,4S)-3,4-bis[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidin-1-yl]-6-oxohexa-2,4-dienoyl]-3-N,4-N-bis[(1S,2R)-2-phenylcyclopropyl]pyrrolidine-3,4-dicarboxamide	1923425: Agonist activity at TLR2/TLR1 in human THP-1 cells	ec50	0.0002	uM
tert-butyl N-[12-[[(3S,4S)-1-[4-[(3S,4S)-3,4-bis[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]-4-[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-3-carbonyl]amino]dodecyl]carbamate	1893014: Agonist activity at TLR1/TLR2 in human THP-1 derived macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay	ec50	0.0002	uM
12-[[(3S,4S)-1-[4-[(3S,4S)-3,4-bis[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]-4-[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-3-carbonyl]amino]dodecyl 2-azidoacetate	1893014: Agonist activity at TLR1/TLR2 in human THP-1 derived macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay	ec50	0.0002	uM
4-[[2-[12-[[(3S,4S)-1-[4-[(3S,4S)-3,4-bis[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]-4-[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-3-carbonyl]amino]dodecoxy]-2-oxoethyl]carbamoyl]benzoic acid	1893014: Agonist activity at TLR1/TLR2 in human THP-1 derived macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay	ec50	0.0002	uM
methyl 12-[[(3S,4S)-1-[4-[(3S,4S)-3,4-bis[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]-4-[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-3-carbonyl]amino]dodecanoate	1893014: Agonist activity at TLR1/TLR2 in human THP-1 derived macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay	ec50	0.0002	uM
methyl 2-[12-[[(3S,4S)-1-[4-[(3S,4S)-3,4-bis[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]-4-[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-3-carbonyl]amino]dodecoxycarbonylamino]acetate	1893014: Agonist activity at TLR1/TLR2 in human THP-1 derived macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay	ec50	0.0002	uM
12-[[(3S,4S)-1-[4-[(3S,4S)-3,4-bis[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]-4-[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-3-carbonyl]amino]dodecyl 2-hydroxyacetate	1893014: Agonist activity at TLR1/TLR2 in human THP-1 derived macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay	ec50	0.0002	uM
2-[[2-[12-[[(3S,4S)-1-[4-[(3S,4S)-3,4-bis[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]-4-[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-3-carbonyl]amino]dodecoxy]-2-oxoethyl]amino]-2-oxoacetic acid	1893014: Agonist activity at TLR1/TLR2 in human THP-1 derived macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay	ec50	0.0002	uM
(3S,4S)-1-[4-[(3S,4S)-3,4-bis[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]-4-N-(12-hydroxydodecyl)-3-N-[(1S,2R)-2-phenylcyclopropyl]pyrrolidine-3,4-dicarboxamide	1893014: Agonist activity at TLR1/TLR2 in human THP-1 derived macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay	ec50	0.0002	uM
(3S,4S)-1-[4-[(3S,4S)-4-[[(1R,2S)-2-phenylcyclopropyl]carbamoyl]-3-[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]-3-N,4-N-di(tetradecyl)pyrrolidine-3,4-dicarboxamide	1923425: Agonist activity at TLR2/TLR1 in human THP-1 cells	ec50	0.0002	uM
(3S,4S)-3-N,4-N-didecyl-1-[4-[(3S,4S)-4-[[(1R,2S)-2-phenylcyclopropyl]carbamoyl]-3-[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]pyrrolidine-3,4-dicarboxamide	1923425: Agonist activity at TLR2/TLR1 in human THP-1 cells	ec50	0.0002	uM
12-[[(3S,4S)-1-[4-[(3S,4S)-3,4-bis[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]-4-[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-3-carbonyl]amino]dodecyl 2-cyanoacetate	1893014: Agonist activity at TLR1/TLR2 in human THP-1 derived macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay	ec50	0.0003	uM
12-[[(3S,4S)-1-[4-[(3S,4S)-3,4-bis[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]-4-[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-3-carbonyl]amino]dodecyl 2-(2,2,2-trichloroethoxycarbonylamino)acetate	1893014: Agonist activity at TLR1/TLR2 in human THP-1 derived macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay	ec50	0.0003	uM
(3S,4S)-1-[4-[(3S,4S)-3,4-bis[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]-4-N-[12-[(4-nitrophenyl)methoxy]dodecyl]-3-N-[(1S,2R)-2-phenylcyclopropyl]pyrrolidine-3,4-dicarboxamide	1893014: Agonist activity at TLR1/TLR2 in human THP-1 derived macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay	ec50	0.0003	uM
(3S,4S)-4-N-[12-[(4-aminophenyl)methoxy]dodecyl]-1-[4-[(3S,4S)-3,4-bis[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]-3-N-[(1S,2R)-2-phenylcyclopropyl]pyrrolidine-3,4-dicarboxamide	1893014: Agonist activity at TLR1/TLR2 in human THP-1 derived macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay	ec50	0.0003	uM
tert-butyl N-[2-[12-[[(3S,4S)-1-[4-[(3S,4S)-3,4-bis[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]-4-[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-3-carbonyl]amino]dodecylamino]-2-oxoethyl]carbamate	1893014: Agonist activity at TLR1/TLR2 in human THP-1 derived macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay	ec50	0.0003	uM
12-[[(3S,4S)-1-[4-[(3S,4S)-3,4-bis[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]-4-[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-3-carbonyl]amino]dodecyl (2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate	1893014: Agonist activity at TLR1/TLR2 in human THP-1 derived macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay	ec50	0.0003	uM
(3S,4S)-1-[4-[(3S,4S)-3,4-bis[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]-4-N-hexyl-3-N-[(1S,2R)-2-phenylcyclopropyl]pyrrolidine-3,4-dicarboxamide	1893014: Agonist activity at TLR1/TLR2 in human THP-1 derived macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay	ec50	0.0003	uM
(3S,4S)-1-[4-[(3S,4S)-3,4-bis[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]-4-N-octyl-3-N-[(1S,2R)-2-phenylcyclopropyl]pyrrolidine-3,4-dicarboxamide	1893014: Agonist activity at TLR1/TLR2 in human THP-1 derived macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay	ec50	0.0003	uM
12-[[(3S,4S)-1-[4-[(3S,4S)-3,4-bis[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]-4-[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-3-carbonyl]amino]dodecyl 3-[2-[2-[2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethoxy]ethoxy]ethoxy]ethoxy]propanoate	1893014: Agonist activity at TLR1/TLR2 in human THP-1 derived macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay	ec50	0.0003	uM
12-[[(3S,4S)-1-[4-[(3S,4S)-3,4-bis[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]-4-[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-3-carbonyl]amino]dodecyl 2-prop-2-ynoxyacetate	1893014: Agonist activity at TLR1/TLR2 in human THP-1 derived macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay	ec50	0.0003	uM
(E)-4-[[2-[12-[[(3S,4S)-1-[4-[(3S,4S)-3,4-bis[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]-4-[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-3-carbonyl]amino]dodecoxy]-2-oxoethyl]amino]-4-oxobut-2-enoic acid	1893014: Agonist activity at TLR1/TLR2 in human THP-1 derived macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay	ec50	0.0003	uM
(3S,4S)-4-N-[8-(4-aminophenyl)octyl]-1-[4-[(3S,4S)-3,4-bis[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]-3-N-[(1S,2R)-2-phenylcyclopropyl]pyrrolidine-3,4-dicarboxamide	1893014: Agonist activity at TLR1/TLR2 in human THP-1 derived macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay	ec50	0.0003	uM
(3S,4S)-3-N,4-N-dibutyl-1-[4-[(3S,4S)-4-[[(1R,2S)-2-phenylcyclopropyl]carbamoyl]-3-[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]pyrrolidine-3,4-dicarboxamide	1923425: Agonist activity at TLR2/TLR1 in human THP-1 cells	ec50	0.0003	uM
(3S,4S)-4-N-octyl-3-N-[(1S,2R)-2-phenylcyclopropyl]-1-[4-[(3S,4S)-4-[[(1R,2S)-2-phenylcyclopropyl]carbamoyl]-3-[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]pyrrolidine-3,4-dicarboxamide	1923425: Agonist activity at TLR2/TLR1 in human THP-1 cells	ec50	0.0003	uM
(3S,4S)-4-N-hexyl-3-N-[(1S,2R)-2-phenylcyclopropyl]-1-[4-[(3S,4S)-4-[[(1R,2S)-2-phenylcyclopropyl]carbamoyl]-3-[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]pyrrolidine-3,4-dicarboxamide	1923425: Agonist activity at TLR2/TLR1 in human THP-1 cells	ec50	0.0003	uM
methyl 10-[[(3S,4S)-1-[4-[(3S,4S)-3,4-bis[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]-4-[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-3-carbonyl]amino]decanoate	1893014: Agonist activity at TLR1/TLR2 in human THP-1 derived macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay	ec50	0.0004	uM
12-[[(3S,4S)-1-[4-[(3S,4S)-3,4-bis[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]-4-[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-3-carbonyl]amino]dodecyl 2-(methoxycarbonylamino)acetate	1893014: Agonist activity at TLR1/TLR2 in human THP-1 derived macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay	ec50	0.0004	uM
(3S,4S)-1-[4-[(3S,4S)-3,4-bis[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]-4-N-hexadecyl-3-N-[(1S,2R)-2-phenylcyclopropyl]pyrrolidine-3,4-dicarboxamide	1893014: Agonist activity at TLR1/TLR2 in human THP-1 derived macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay	ec50	0.0005	uM
(3S,4S)-1-[4-[(3S,4S)-3,4-bis[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]pyrrolidine-1-carbonyl]benzoyl]-4-N-(10-hydroxydecyl)-3-N-[(1S,2R)-2-phenylcyclopropyl]pyrrolidine-3,4-dicarboxamide	1893014: Agonist activity at TLR1/TLR2 in human THP-1 derived macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay	ec50	0.0005	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Nickel	decreases expression, increases expression	3
Silicon Dioxide	decreases expression, increases expression	2
GSK-J4	decreases expression	1
sotorasib	affects cotreatment, decreases expression	1
Asian ginseng	affects cotreatment, decreases expression	1
2-anisidine	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
deoxynivalenol	decreases expression	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
tetrabromobisphenol A	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
lipopolysaccharide, E. coli O26-B6	decreases expression	1
abrine	decreases expression	1
3,5-bis(2-fluorobenzylidene)piperidin-4-one	decreases reaction, increases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Resveratrol	decreases reaction, increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression	1
Air Pollutants, Occupational	decreases expression	1
Arsenic	increases expression	1
Benzene	increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Cadmium	increases expression	1
Cisplatin	increases expression	1
Curcumin	increases expression, decreases reaction	1

ChEMBL screening assays

59 unique, capped per target: 59 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4392899	Binding	Induction of human TLR1 homodimerization expressed in insect Hi5 cells by size exclusion chromatography	Structural Basis of TLR2/TLR1 Activation by the Synthetic Agonist Diprovocim. — J Med Chem

Cellosaurus cell lines

8 cell lines: 5 transformed cell line, 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8QW	Abcam HCT 116 TLR1 KO	Cancer cell line	Male
CVCL_B9TA	Abcam A-549 TLR1 KO	Cancer cell line	Male
CVCL_E1DH	Ubigene THP-1 TLR1 KO	Cancer cell line	Male
CVCL_UF27	HEK-Blue hTLR2 KO-TLR1/6	Transformed cell line	Female
CVCL_UF28	HEK-Blue hTLR2-TLR1	Transformed cell line	Female
CVCL_UF29	HEK-Blue hTLR2-TLR6	Transformed cell line	Female
CVCL_Y385	293/hTLR1-HA	Transformed cell line	Female
CVCL_Y417	293/hTLR1-TLR2	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00056667	PHASE4	COMPLETED	Relaxation Response Training for the Treatment of Rheumatoid Arthritis
NCT00094341	PHASE4	COMPLETED	Preference of Rheumatoid Arthritis (RA) Patients of Enbrel® (Etanercept) Auto-Injector Versus Enbrel® Pre-Filled Syringes
NCT00099554	PHASE4	COMPLETED	Effectiveness and Safety of Enbrel® (Etanercept) in Rheumatoid Arthritis Subjects Who Have Failed Remicade® (Infliximab)
NCT00111410	PHASE4	COMPLETED	Evaluating the Effect of Anakinra (r-metHuIL-1ra) on Vaccine AntibodyResponse in Subjects With Rheumatoid Arthritis (RA)
NCT00115219	PHASE4	COMPLETED	Evaluating Efficacy and Safety of Etanercept 50 mg Twice Weekly (BIW) in Rheumatoid Arthritis (RA) Subjects Who Are Sub-Optimal Responders to Etanercept 50 mg Once Weekly (QW)
NCT00121043	PHASE4	COMPLETED	Evaluating Kineret® (Anakinra) in Rheumatoid Arthritis (RA) Subjects Using aSelf-Reported Questionnaire
NCT00132418	PHASE4	COMPLETED	Study of Enbrel in Rheumatoid Arthritis (RA) Subjects With Comorbid Disorders
NCT00157872	PHASE4	COMPLETED	A Study of Rofecoxib Versus Naproxen in the Treatment of Chinese Patient With Rheumatoid Arthritis (0966-231)
NCT00195494	PHASE4	COMPLETED	Study Comparing Etanercept and Methotrexate vs. Methotrexate Alone in Rheumatoid Arthritis
NCT00208364	PHASE4	TERMINATED	A Two Centre Study to Assess the Long-term Performance of the Pinnacle™ Cup With a Metal-on-Metal Bearing in Primary Total Hip Replacement
NCT00208377	PHASE4	TERMINATED	A Multi-centre Study to Assess the Long-term Performance of the DePuy ASR™ System in Primary Hip Resurfacing Surgery
NCT00208390	PHASE4	TERMINATED	A Multi-centre Study to Assess the Long-term Performance of the Summit™ Hip in Primary Total Hip Replacement
NCT00208429	PHASE4	WITHDRAWN	A Multi-centre Study to Assess the Long-term Performance of the Pinnacle™ Cup With a Polyethylene-on-metal Bearing in Primary Total Hip Replacement
NCT00208455	PHASE4	TERMINATED	A Multi-centre Study to Assess the Long-term Performance of the DePuy PROXIMA™ Hip in Primary Total Hip Replacement
NCT00209859	PHASE4	COMPLETED	Methotrexate and Cyclosporine in Treatment of Early Rheumatoid Arthritis
NCT00216177	PHASE4	UNKNOWN	Comparison of Adalimumab and Infliximab Treatment of Rheumatoid Arthritis
NCT00233558	PHASE4	TERMINATED	Open-Label Steroid Reduction Study of Adalimumab With Methotrexate in Patients With Active Rheumatoid Arthritis
NCT00234234	PHASE4	COMPLETED	Predictors of the Response to Adalimumab in Rheumatoid Arthritis
NCT00234897	PHASE4	COMPLETED	Efficacy of HUMIRA in Subjects With Active Rheumatoid Arthritis
NCT00244556	PHASE4	COMPLETED	Study Comparing Enbrel (Etanercept) Plus Methotrexate Versus Enbrel Alone in Active Rheumatoid Arthritis Despite Current Methotrexate Therapy
NCT00252668	PHASE4	COMPLETED	Study Evaluating the Combination of Etanercept and Methotrexate in Rheumatoid Arthritis Subjects
NCT00259610	PHASE4	COMPLETED	Treatment of Early Aggressive Rheumatoid Arthritis (TEAR)
NCT00291915	PHASE4	UNKNOWN	Multicenter Randomized Prospective Trial Comparing Methotrexate Alone or in Combination With Adalimumab in Early Arthritis
NCT00319917	PHASE4	COMPLETED	A Double Blind Placebo Controlled Study to Assess the Efficacy on Joint Damage in RA Patients
NCT00334620	PHASE4	COMPLETED	Effectiveness of Radon Spa Therapy in Multimodal Rehabilitative Treatment of Rheumatoid Arthritis
NCT00346294	PHASE4	COMPLETED	An Open-Label Study to Assess the Rate of Failure of an Enbrel® (Etanercept) SureClick™ Auto-injector in Subjects With Rheumatoid Arthritis
NCT00356473	PHASE4	COMPLETED	Effects of Atorvastatin on Disease Activity and HDL Cholesterol Function in Patients With Rheumatoid Arthritis
NCT00369187	PHASE4	COMPLETED	Study of a Large Protein Molecule Administered With Escalating Doses of Recombinant Human Hyaluronidase
NCT00385528	PHASE4	COMPLETED	Effects of a Multi-Faceted Psychiatric Intervention Targeted at the Complex Medically Ill: a Randomized Controlled Trial
NCT00396747	PHASE4	COMPLETED	A Comparison of Methotrexate Alone or Combined to Infliximab or to Pulse Methylprednisolone in Early Rheumatoid Arthritis: A Magnetic Resonance Imaging Study
NCT00420927	PHASE4	COMPLETED	Study of the Optimal Protocol for Methotrexate and Adalimumab Combination Therapy in Early Rheumatoid Arthritis
NCT00422227	PHASE4	COMPLETED	Study Comparing Etanercept With Usual DMARD Therapy in Subjects With Rheumatoid Arthritis in the Asia Pacific Region
NCT00424502	PHASE4	COMPLETED	A Study of MabThera (Rituximab) in Patients With Rheumatoid Arthritis Who Have Had an Inadequate Response to a TNF-Blocker.
NCT00434200	PHASE4	UNKNOWN	Rheumatoid Arthritis Patients in Training
NCT00439062	PHASE4	COMPLETED	Treatment of Rheumatoid Arthritis With Roxithromycin
NCT00447759	PHASE4	COMPLETED	The Standard Care Versus Celecoxib Outcome Trial
NCT00462072	PHASE4	COMPLETED	Centocor Microarray Study of Patients
NCT00462345	PHASE4	COMPLETED	A Study of MabThera (Rituximab) in Combination With Methotrexate in Patients With Rheumatoid Arthritis Who Have Had an Inadequate Response to Anti-TNF Therapies.
NCT00480272	PHASE4	COMPLETED	Prospective Study on Intensive Early Rheumatoid Arthritis Treatment
NCT00502853	PHASE4	COMPLETED	A Pilot Study of MabThera (Rituximab) Evaluated by MRI in Patients With Rheumatoid Arthritis.