TLR2

Summary

TLR2 (toll like receptor 2, HGNC:11848) is a protein-coding gene on chromosome 4q31.3, encoding Toll-like receptor 2 (O60603). Cooperates with LY96 to mediate the innate immune response to bacterial lipoproteins and other microbial cell wall components.

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. This protein is a cell-surface protein that can form heterodimers with other TLR family members to recognize conserved molecules derived from microorganisms known as pathogen-associated molecular patterns (PAMPs). Activation of TLRs by PAMPs leads to an up-regulation of signaling pathways to modulate the host’s inflammatory response. This gene is also thought to promote apoptosis in response to bacterial lipoproteins. This gene has been implicated in the pathogenesis of several autoimmune diseases. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 7097 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 122 total
• Phenotypes (HPO): 9
• Druggable target: yes
• MANE Select transcript: NM_001318789

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11848
Approved symbol	TLR2
Name	toll like receptor 2
Location	4q31.3
Locus type	gene with protein product
Status	Approved
Aliases	TIL4, CD282
Ensembl gene	ENSG00000137462
Ensembl biotype	protein_coding
OMIM	603028
Entrez	7097

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 31 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000260010, ENST00000642580, ENST00000642700, ENST00000643087, ENST00000643501, ENST00000645889, ENST00000646219, ENST00000646900, ENST00000714431, ENST00000714432, ENST00000714433, ENST00000714434, ENST00000714435, ENST00000714436, ENST00000855786, ENST00000855787, ENST00000855788, ENST00000855789, ENST00000855790, ENST00000855791, ENST00000855792, ENST00000914233, ENST00000914234, ENST00000966792, ENST00000966793, ENST00000966794, ENST00000966795, ENST00000966796, ENST00000966797, ENST00000966798, ENST00000966799, ENST00000966800

RefSeq mRNA: 8 — MANE Select: NM_001318789 NM_001318787, NM_001318789, NM_001318790, NM_001318791, NM_001318793, NM_001318795, NM_001318796, NM_003264

CCDS: CCDS3784

Canonical transcript exons

ENST00000642700 — 3 exons

Exon	Start	End
ENSE00003830773	153702892	153706260
ENSE00004023984	153684280	153684360
ENSE00004023988	153687902	153688047

Expression profiles

Bgee: expression breadth ubiquitous, 214 present calls, max score 98.19.

FANTOM5 (CAGE): breadth broad, TPM avg 20.9183 / max 2550.2779, expressed in 813 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
50101	20.0249	807
50102	0.8934	123

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	98.19	gold quality
mononuclear cell	CL:0000842	98.03	gold quality
leukocyte	CL:0000738	97.94	gold quality
blood	UBERON:0000178	97.50	gold quality
granulocyte	CL:0000094	95.69	gold quality
right lung	UBERON:0002167	94.01	gold quality
upper lobe of left lung	UBERON:0008952	92.32	gold quality
upper lobe of lung	UBERON:0008948	91.98	gold quality
spleen	UBERON:0002106	91.39	gold quality
bone marrow	UBERON:0002371	91.04	gold quality
cartilage tissue	UBERON:0002418	90.84	gold quality
bone marrow cell	CL:0002092	88.86	gold quality
lung	UBERON:0002048	88.78	gold quality
periodontal ligament	UBERON:0008266	87.78	gold quality
vermiform appendix	UBERON:0001154	87.15	gold quality
descending thoracic aorta	UBERON:0002345	86.77	gold quality
lower lobe of lung	UBERON:0008949	86.75	gold quality
tibial nerve	UBERON:0001323	85.97	gold quality
minor salivary gland	UBERON:0001830	85.90	gold quality
thoracic aorta	UBERON:0001515	85.39	gold quality
gall bladder	UBERON:0002110	85.25	gold quality
ascending aorta	UBERON:0001496	85.16	gold quality
visceral pleura	UBERON:0002401	84.56	gold quality
omental fat pad	UBERON:0010414	84.17	gold quality
peritoneum	UBERON:0002358	84.11	gold quality
left uterine tube	UBERON:0001303	83.79	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	83.70	gold quality
adipose tissue of abdominal region	UBERON:0007808	83.55	gold quality
right coronary artery	UBERON:0001625	83.28	gold quality
trabecular bone tissue	UBERON:0002483	83.27	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	43.88
E-GEOD-84465	yes	39.36
E-HCAD-35	yes	35.20
E-MTAB-9221	yes	19.54
E-MTAB-8498	yes	11.79
E-MTAB-9801	yes	6.21
E-CURD-119	yes	4.50
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
DEFB131A	Activation
LGALS9	Activation

Upstream regulators (CollecTRI, top): CREB1, DICER1, ESR1, HBP1, HIF1A, IRF1, IRF6, NFKB1, NFKB, NFKBIA, NR3C1, PPARA, PPARG, RELA, SP1, SPI1, STAT5A, STAT5B, TFAP2A, TRPV4

miRNA regulators (miRDB)

54 targeting TLR2, 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-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-567	99.63	68.57	1219
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-6165	99.44	67.12	1389
HSA-MIR-4318	99.38	66.94	1505
HSA-MIR-548V	99.29	69.47	1157
HSA-MIR-410-3P	99.27	69.98	2457
HSA-MIR-10399-5P	99.17	69.87	2610

Literature-anchored findings (GeneRIF, showing 40)

• TLR2 stimulation resulted in the release of the IL-12 inhibitory p40 homodimer, producing conditions that are predicted to favor Th2 development, also resulted in preferential induction of IL-8 and p19/IL-23. (PMID:11477091)
• These results indicate that the direct interaction of SP-A with TLR2 alters PGN-induced cell signaling (PMID:11724772)
• identification of role in novel signal transduction pathway utilized by exracellular HSP70 (PMID:11836257)
• stimulation of signal pathway by HSP70 (PMID:11842086)
• Glucocorticoids synergistically enhance nontypeable Haemophilus influenzae-induced Toll-like receptor 2 expression via a negative cross-talk with p38 MAP kinase. (PMID:11867630)
• TLR2 initiated the signaling pathway for p38 in response to bacterial products /LPS/ (PMID:11867688)
• signaling events by TLR2 and TLR4 agonists are similar but there are distinct differences in the responses elicited by two bacterial products (PMID:11877429)
• Non-LPS components of Chlamydia pneumoniae stimulate cytokine production through Toll-like receptor 2-dependent pathways. (PMID:11932927)
• mycoplasmal lipoproteins induce caspases-dependent necrotic and apoptotic cell death in lymphocytes and monocytes/macrophages, which is partially induced by TLR2-mediated signaling. (PMID:12061629)
• involvement in cell activation by mannuronic acid polymers (PMID:12089142)
• report that wild-type measles virus but not vaccine strains activate cells via the TLR2, and this is a property of the hemagglutinin (H) protein (PMID:12163593)
• TLR2 has a role in mediating signaling responses to Aspergillus fumigatus (PMID:12171914)
• Porphyromonas gingivalis fimbriae activate human peripheral blood monocytes utilizing TLR2, CD14 and CD11a/CD18 as cellular receptors. (PMID:12207338)
• Susceptibility of human dendritic cells (DCs) to measles virus (MV) depends on their activation stages in conjunction with the level of CDw150: role of Toll stimulators in DC maturation and MV amplification (PMID:12270725)
• glucocorticoids synergistically enhance NTHi-induced TLR2 expression via specific up-regulation of the MAPK phosphatase-1 (MKP-1) that, in turn, leads to dephosphorylation and inactivation of p38 MAPK (PMID:12356755)
• TLR4 was found to be involved in PM(2.5-10) and Pseudomonas-induced activation, whereas TLR2 activation was induced by both Gram+ and Gram- bacteria and by PM. (PMID:12397021)
• An extensively associated dimer is observed in the crystal structure of a mutant of the TIR domain of TLR2. (PMID:12437972)
• lipopolysaccharide may induce proliferation of periodontal epithelial cells by upregulating keratinocyte growth factor 1 expression via the CD14 and Toll-like receptor signaling pathway (PMID:12438323)
• On cell surface. LPS response inhibited with mAb specific for TLR2.LPS response of epidermal keratinocytes might be mediated by TLR2-dependent recognition of non-LPS bacterial components contaminating commercial LPS preparations. (PMID:12443841)
• innate immune response of monocytes against M. lepraeis is mediated by TLR2, the mutation in the intracellular domain of TLR2 gene is associated with IL-12 production in lepromatous leprosy (PMID:12445799)
• TLR2 and TLR4 mRNA were significantly up-regulated by IL-10 in monocyte cells that were adherent compared to those nonadherent. (PMID:12525572)
• The relative absence of TLR2 protein expression by intestinal epithelial cells may be important in preventing chronic proinflammatory cytokine secretion in response to commensal Gram-positive bacteria in the gut. (PMID:12538701)
• findings suggest that oral treponemes and their outer membrane extracts activate human gingival epithelial cells through TLR2 (PMID:12540550)
• participates in the innate immune response to stimulation by bacterial products in periodontal tissues (PMID:12588460)
• innate immune recognition of LTA via LBP, CD14, and TLR-2 represents an important mechanism in the pathogenesis of systemic complications in the course of infectious diseases brought about by Gram-positive pathogens. while TLR-4 and MD-2 are not involved. (PMID:12594207)
• Review. Maturation of dendritic cells (DCs) and cytokine induction by the cell wall skeleton of Mycobacterium bovis bacillus Calmette-Guerin are induced via both TLR2 and TLR4. (PMID:12630564)
• Expression of the Arg677Trp variant of human TLR2, which was identified in Korean patients with lepromous leprosy, was not able to mediate a response to either M. leprae or M. tuberculosis. (PMID:12646604)
• role in synovial fibroblast activation in rheumatoid arthritis (PMID:12651614)
• Human cytomegalovirus activates inflammatory cytokine responses via CD14 and Toll-like receptor 2 (PMID:12663765)
• Costimulation with TLR2 (or TLR9) and TLR4 induces synergistic release of Th1 cytokines, IFN-gamma and TNF-alpha, and additive HIV-LTR trans-activation and HIV replication, as measured by p24 antigen release from HIV-1 transgenic mouse spleen cells. (PMID:12734363)
• First comparative investigation in highly purified, monocyte-depleted neutrophil populations shows a distinct and separate role for TLR2, compared with TLR4, in neutrophil responses and neutrophil survival. (PMID:12734376)
• Data show that Toll-like receptors TLR2 and TLR4 were expressed on dendritic cells, whereas only TLR2 was weakly detected on Langerhans cells. (PMID:12810071)
• TLR2 is an endocytic receptor that channels ligands into the major histocompatibility complex class II presentation pathway for stimulation of specific CD4+ T cells. (PMID:12816980)
• Zymosan cosediments the soluble form of recombinant TLR2 possessing the putative extracellular domain (sTLR2); sTLR2 directly binds to zymosan with an apparent binding constant of 48 nM. (PMID:12817025)
• contains multiple binding domains for ligands that may contribute to the characterization of its promiscuous molecular pattern recognition (PMID:12860988)
• Human TLR2, but not TLR4, can mediate cellular activation by heat-killed Brucella abortus (HKBA); human embryonic kidney 293 cells, which do not respond to HKBA, are made responsive by transfecting TLR2, but not TLR4 or TLR9. (PMID:12874236)
• Results show that the surface receptors TLR2/4 and CD14 are essential for in vitro cellular activation induced by Neisseria meningitidis lipopolysaccharide-containing outer membrane vesicles and purified lipopolysaccharides. (PMID:12942028)
• TLR-2 on human NK cells is upregulated and stimulated by Leishmania major lipophosphoglycan (LPG), a phosphoglycan belonging to a family of unique Leishmania glycoconjugates (PMID:12946842)
• Toll-like receptor 2 mediates beta-defensin 2 gene induction through NF-kappaB in lung epithelial cells. (PMID:12958190)
• In addition to TLR2, the activation of NF-kappaB by H.8/Lip in HEK cells was enhanced upon coexpression of TLR1 but not TLR6. (PMID:12966099)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tlr2	ENSDARG00000037758
mus_musculus	Tlr2	ENSMUSG00000027995
rattus_norvegicus	Tlr2	ENSRNOG00000009822

Paralogs (22): IGFALS (ENSG00000099769), TLR8 (ENSG00000101916), LRRC17 (ENSG00000128606), RXFP2 (ENSG00000133105), CD180 (ENSG00000134061), TLR4 (ENSG00000136869), 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), TLR7 (ENSG00000196664), LRIT2 (ENSG00000204033), LRRC3C (ENSG00000204913)

Protein

Protein identifiers

Toll-like receptor 2 — O60603 (reviewed: O60603)

Alternative names: Toll/interleukin-1 receptor-like protein 4

All UniProt accessions (7): A0A0S2Z4L7, A0A0S2Z4S4, A0A2R8Y4N9, A0A2R8Y7R7, A0A2R8YHF6, A0AAQ5BI37, O60603

UniProt curated annotations — full annotation on UniProt →

Function. Cooperates with LY96 to mediate the innate immune response to bacterial lipoproteins and other microbial cell wall components. Cooperates with TLR1 or TLR6 to mediate the innate immune response to bacterial lipoproteins or lipopeptides. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. May also activate immune cells and promote apoptosis in response to the lipid moiety of lipoproteins. Recognizes mycoplasmal macrophage-activating lipopeptide-2kD (MALP-2), soluble tuberculosis factor (STF), phenol-soluble modulin (PSM) and B.burgdorferi outer surface protein A lipoprotein (OspA-L) cooperatively with TLR6. Stimulation of monocytes in vitro with M.tuberculosis PstS1 induces p38 MAPK and ERK1/2 activation primarily via this receptor, but also partially via TLR4. MAPK activation in response to bacterial peptidoglycan also occurs via this receptor. Acts as a receptor for M.tuberculosis lipoproteins LprA, LprG, LpqH and PstS1, some lipoproteins are dependent on other coreceptors (TLR1, CD14 and/or CD36); the lipoproteins act as agonists to modulate antigen presenting cell functions in response to the pathogen. M.tuberculosis HSP70 (dnaK) but not HSP65 (groEL-2) acts via this protein to stimulate NF-kappa-B expression. Recognizes M.tuberculosis major T-antigen EsxA (ESAT-6) which inhibits downstream MYD88-dependent signaling (shown in mouse). Forms activation clusters composed of several receptors depending on the ligand, these clusters trigger signaling from the cell surface and subsequently are targeted to the Golgi in a lipid-raft dependent pathway. Forms the cluster TLR2:TLR6:CD14:CD36 in response to diacylated lipopeptides and TLR2:TLR1:CD14 in response to triacylated lipopeptides. Required for normal uptake of M.tuberculosis, a process that is inhibited by M.tuberculosis LppM.

Subunit / interactions. Interacts with LY96, TLR1 and TLR6 (via extracellular domain). 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. Binds MYD88 (via TIR domain). Interacts with TICAM1. Interacts with CNPY3. Interacts with ATG16L1. Interacts with PPP1R11. Interacts with TICAM2. Interacts with TIRAP. (Microbial infection) Interacts with M.tuberculosis EsxA. (Microbial infection) Interacts with M.bovis MPB83. (Microbial infection) Interacts with Staphylococcus aureus protein SSL5.

Subcellular location. Membrane. Cytoplasmic vesicle. Phagosome membrane. Membrane raft.

Tissue specificity. Highly expressed in peripheral blood leukocytes, in particular in monocytes, in bone marrow, lymph node and in spleen. Also detected in lung and in fetal liver. Levels are low in other tissues.

Post-translational modifications. Glycosylation of Asn-442 is critical for secretion of the N-terminal ectodomain of TLR2. Ubiquitinated at Lys-754 by PPP1R11, leading to its degradation. Deubiquitinated by USP2.

Domain organisation. Ester-bound lipid substrates are bound through a crevice formed between the LRR 11 and LRR 12. The ATG16L1-binding motif mediates interaction with ATG16L1.

Induction. (Microbial infection) In macrophages, induced by SARS-CoV-2 infection.

Polymorphism. Genetic variations in TLR2 are associated with susceptibility to leprosy [MIM:246300]. Leprosy is a chronic disease associated with depressed cellular (but not humoral) immunity, the bacterium requires a lower temperature than 37 degrees Celsius and thrives particularly in peripheral Schwann cells and macrophages. The Trp-677 polymorphism in the intracellular domain of TLR2 has a role in susceptibility to lepromatous leprosy. Wild-type TLR2 mediates CD14-enhanced Mycobacterium leprae-dependent activation of NFKB1, but TLR2 containing the Trp-677 polymorphism did not. The impaired function of the Trp-677 polymorphism provides a molecular mechanism for the poor cellular immune response associated with lepromatous leprosy.

Similarity. Belongs to the Toll-like receptor family.

RefSeq proteins (8): NP_001305716, NP_001305718, NP_001305719, NP_001305720, NP_001305722, NP_001305724, NP_001305725, NP_003255 (=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: PF00560, PF01463, PF01582, PF13855

UniProt features (127 total): strand 33, helix 26, repeat 19, turn 10, mutagenesis site 10, sequence variant 9, glycosylation site 4, disulfide bond 3, sequence conflict 3, topological domain 2, domain 2, signal peptide 1, chain 1, short sequence motif 1, site 1, transmembrane region 1, cross-link 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
2Z80	X-RAY DIFFRACTION	1.8
2Z7X	X-RAY DIFFRACTION	2.1
6NIG	X-RAY DIFFRACTION	2.35
1FYX	X-RAY DIFFRACTION	2.8
1FYW	X-RAY DIFFRACTION	3
1O77	X-RAY DIFFRACTION	3.2
8AR0	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60603-F1	87.87	0.63

Functional residue map

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

Catalytic / active sites (1): 349 (interaction with bacterial lipopeptide)

Post-translational modifications (1): 754

Disulfide bonds (3): 30–36, 353–382, 432–454

Glycosylation sites (4): 114, 199, 414, 442

Mutagenesis-validated functional residues (10):

Position	Phenotype
114	prevents addition of n-glycans. reduces secretion of the n-terminal ectodomain.
199	prevents addition of n-glycans. reduces secretion of the n-terminal ectodomain.
416	prevents addition of n-glycans. reduces secretion of the n-terminal ectodomain.
442	prevents addition of n-glycans. prevents secretion of the n-terminal ectodomain.
681	abolishes the interaction with myd88. no effect on oligomerization or on the structure of the tir domain.
709	reduced protein stability.
714	reduced protein stability.
742–743	reduced protein stability.
751	reduced protein stability.
754	loss of ppp1r11-mediated ubiquitination and degradation.

Function

Pathways and Gene Ontology

Reactome pathways

12 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-168188	Toll Like Receptor TLR6: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-6798695	Neutrophil degranulation
R-HSA-9637628	Modulation by Mtb of host immune system
R-HSA-9705671	SARS-CoV-2 activates/modulates innate and adaptive immune responses
R-HSA-9833110	RSV-host interactions

MSigDB gene sets: 523 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_COGNITION, GOBP_BEHAVIOR, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_POSITIVE_REGULATION_OF_TYPE_I_INTERFERON_PRODUCTION, GOBP_MYELOID_CELL_DEVELOPMENT, GOBP_INFLAMMATORY_RESPONSE, GOBP_POSITIVE_REGULATION_OF_INTERLEUKIN_8_PRODUCTION, GOBP_SYNAPSE_ASSEMBLY, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, GOCC_SECRETORY_GRANULE, MODULE_545

GO Biological Process (38): toll-like receptor signaling pathway (GO:0002224), apoptotic process (GO:0006915), inflammatory response (GO:0006954), immune response (GO:0006955), signal transduction (GO:0007165), learning (GO:0007612), positive regulation of gene expression (GO:0010628), microglia development (GO:0014005), positive regulation of Wnt signaling pathway (GO:0030177), positive regulation of chemokine production (GO:0032722), positive regulation of interferon-beta production (GO:0032728), positive regulation of interleukin-12 production (GO:0032735), positive regulation of interleukin-18 production (GO:0032741), 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), toll-like receptor 2 signaling pathway (GO:0034134), toll-like receptor TLR6:TLR2 signaling pathway (GO:0038124), detection of triacyl bacterial lipopeptide (GO:0042495), detection of diacyl bacterial lipopeptide (GO:0042496), 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), negative regulation of phagocytosis (GO:0050765), defense response to Gram-positive bacterium (GO:0050830), obsolete positive regulation of NF-kappaB transcription factor activity (GO:0051092), defense response to virus (GO:0051607), negative regulation of synapse assembly (GO:0051964), cellular response to bacterial lipopeptide (GO:0071221), cellular response to lipoteichoic acid (GO:0071223), cellular response to type II interferon (GO:0071346), cellular response to diacyl bacterial lipopeptide (GO:0071726), cellular response to triacyl bacterial lipopeptide (GO:0071727), positive regulation of cellular response to macrophage colony-stimulating factor stimulus (GO:1903974), positive regulation of matrix metallopeptidase secretion (GO:1904466), immune system process (GO:0002376), lipopolysaccharide-mediated signaling pathway (GO:0031663)

GO Molecular Function (13): lipopolysaccharide binding (GO:0001530), amyloid-beta binding (GO:0001540), lipopolysaccharide immune receptor activity (GO:0001875), transmembrane signaling receptor activity (GO:0004888), Toll-like receptor binding (GO:0035325), signaling receptor activity (GO:0038023), pattern recognition receptor activity (GO:0038187), triacyl lipopeptide binding (GO:0042497), identical protein binding (GO:0042802), peptidoglycan binding (GO:0042834), protein-containing complex binding (GO:0044877), protein binding (GO:0005515), NAD+ nucleosidase activity, cyclic ADP-ribose generating (GO:0061809)

GO Cellular Component (14): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), cell surface (GO:0009986), secretory granule membrane (GO:0030667), phagocytic vesicle membrane (GO:0030670), Toll-like receptor 1-Toll-like receptor 2 protein complex (GO:0035354), Toll-like receptor 2-Toll-like receptor 6 protein complex (GO:0035355), signaling receptor complex (GO:0043235), membrane raft (GO:0045121), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Toll Like Receptor 2 (TLR2) Cascade	2
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 Cascades	1
Innate Immune System	1
Infection with Mycobacterium tuberculosis	1
SARS-CoV-2-host interactions	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	5
cellular anatomical structure	5
cytoplasm	3
detection of bacterial lipopeptide	2
signaling receptor activity	2
binding	2
plasma membrane signaling receptor complex	2
pattern recognition receptor signaling pathway	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	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
learning or memory	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
microglia differentiation	1
glial cell development	1
myeloid cell development	1
positive regulation of signal transduction	1
Wnt signaling pathway	1
regulation of Wnt signaling pathway	1
chemokine production	1
regulation of chemokine production	1
positive regulation of type I interferon production	1
interferon-beta production	1
regulation of interferon-beta production	1
interleukin-12 production	1
regulation of interleukin-12 production	1
interleukin-18 production	1
regulation of interleukin-18 production	1
interleukin-6 production	1
regulation of interleukin-6 production	1

Protein interactions and networks

STRING

4916 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TLR2	TIRAP	P58753	998
TLR2	CLEC7A	Q9BXN2	998
TLR2	HMGB1	P09429	996
TLR2	CD36	P16671	996
TLR2	SCARB2	Q14108	996
TLR2	SCARB1	Q8WTV0	996
TLR2	HSPA4	P34932	992
TLR2	LY96	Q9Y6Y9	992
TLR2	TLR4	O00206	990
TLR2	MYD88	P78397	990
TLR2	HSPA1A	P08107	988
TLR2	BGN	P13247	986
TLR2	TLR1	Q15399	986
TLR2	TLR10	Q9BXR5	986
TLR2	TLR6	Q9Y2C9	986

IntAct

53 interactions, top by confidence:

A	B	Type	Score
MYD88	TLR2	psi-mi:“MI:0407”(direct interaction)	0.740
TLR2	MYD88	psi-mi:“MI:0915”(physical association)	0.740
MYD88	TLR2	psi-mi:“MI:0403”(colocalization)	0.740
TLR2	TLR6	psi-mi:“MI:0915”(physical association)	0.680
TLR6	TLR2	psi-mi:“MI:0915”(physical association)	0.680
TLR2	EGFR	psi-mi:“MI:0915”(physical association)	0.680
EGFR	TLR2	psi-mi:“MI:0915”(physical association)	0.680
CXCR4	TLR2	psi-mi:“MI:0407”(direct interaction)	0.590
CXCR4	TLR2	psi-mi:“MI:0914”(association)	0.590
TLR2	CXCR4	psi-mi:“MI:0914”(association)	0.590
TLR2	TLR2	psi-mi:“MI:0915”(physical association)	0.580
TLR2	ZG16B	psi-mi:“MI:0915”(physical association)	0.580
TLR2	TLR10	psi-mi:“MI:0915”(physical association)	0.570
TLR2	BMPR1A	psi-mi:“MI:0914”(association)	0.530
TLR1	TLR2	psi-mi:“MI:0915”(physical association)	0.510
TLR2	TLR1	psi-mi:“MI:0915”(physical association)	0.510
TLR2	CD14	psi-mi:“MI:0407”(direct interaction)	0.440
porB	TLR2	psi-mi:“MI:0407”(direct interaction)	0.440
BGN	TLR2	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (68): TLR2 (Two-hybrid), TLR2 (PCA), TLR2 (Reconstituted Complex), TLR2 (Far Western), TLR2 (Far Western), TLR2 (Affinity Capture-Western), TLR2 (Affinity Capture-Western), gag (Affinity Capture-Western), STAT5A (Affinity Capture-MS), TMEM214 (Affinity Capture-MS), ACVR2A (Affinity Capture-MS), BMPR1A (Affinity Capture-MS), ITPRIP (Affinity Capture-MS), USP33 (Affinity Capture-MS), STK11IP (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

8 interactions.

A	Effect	B	Mechanism
S	“up-regulates activity”	TLR2	binding
TLR2	“down-regulates activity”	NfKb-p65/p50
BGLF5	“down-regulates quantity by repression”	TLR2	“post transcriptional regulation”
“muramyl dipeptide”	“up-regulates activity”	TLR2	binding
TLR2	“up-regulates activity”	MYD88	binding
TLR2	“up-regulates activity”	TIRAP	binding
TLR2	“up-regulates activity”	TICAM1	binding
TLR2	“up-regulates activity”	TICAM2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 32 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
MyD88 deficiency (TLR2/4)	6	156.8×	2e-10
IRAK4 deficiency (TLR2/4)	6	149.0×	2e-10
MyD88:MAL(TIRAP) cascade initiated on plasma membrane	7	46.3×	1e-08
ER-Phagosome pathway	6	33.9×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of interleukin-8 production	5	45.2×	1e-05
positive regulation of tumor necrosis factor production	7	39.7×	2e-07
positive regulation of interleukin-6 production	6	37.1×	4e-06
positive regulation of ERK1 and ERK2 cascade	5	15.8×	5e-04
inflammatory response	9	12.6×	4e-06
cell surface receptor signaling pathway	5	11.9×	1e-03
positive regulation of cell migration	5	11.4×	1e-03
immune response	6	10.5×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	84
Likely benign	15
Benign	8

Top pathogenic / likely-pathogenic (0)

SpliceAI

295 predictions. Top by Δscore:

Variant	Effect	Δscore
4:153701619:A:G	donor_gain	0.9900
4:153702886:TTGTA:T	acceptor_loss	0.9900
4:153702887:TGTA:T	acceptor_loss	0.9900
4:153702888:GTAG:G	acceptor_loss	0.9900
4:153702889:TA:T	acceptor_loss	0.9900
4:153702890:A:AG	acceptor_gain	0.9900
4:153702891:G:GG	acceptor_gain	0.9900
4:153701619:A:AG	donor_gain	0.9800
4:153701623:GT:G	donor_gain	0.9800
4:153701635:G:GG	donor_gain	0.9800
4:153702884:A:AG	acceptor_gain	0.9800
4:153702885:T:G	acceptor_gain	0.9800
4:153702891:GGTT:G	acceptor_gain	0.9800
4:153702335:C:T	donor_gain	0.9400
4:153702965:G:GT	donor_gain	0.9400
4:153701611:A:AG	donor_gain	0.9300
4:153702890:AG:A	acceptor_gain	0.9300
4:153702891:GG:G	acceptor_gain	0.9300
4:153701622:A:T	donor_gain	0.9100
4:153702368:TCCCA:T	donor_gain	0.9100
4:153702890:AGGTT:A	acceptor_gain	0.9100
4:153702891:GGTTG:G	acceptor_gain	0.9100
4:153701606:C:CA	donor_gain	0.9000
4:153701612:T:G	donor_gain	0.8900
4:153702323:A:G	donor_gain	0.8900
4:153702891:GGT:G	acceptor_gain	0.8900
4:153701610:G:A	donor_gain	0.8800
4:153702887:T:TA	acceptor_gain	0.8800
4:153701581:A:G	donor_gain	0.8600
4:153701609:TG:T	donor_gain	0.8600

AlphaMissense

5194 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:153704942:T:C	F679L	0.998
4:153704944:C:A	F679L	0.998
4:153704944:C:G	F679L	0.998
4:153704837:T:C	F644L	0.997
4:153704839:T:A	F644L	0.997
4:153704839:T:G	F644L	0.997
4:153704841:T:A	V645D	0.997
4:153705018:C:T	S704F	0.997
4:153705041:T:A	W712R	0.997
4:153705041:T:C	W712R	0.997
4:153704971:T:A	N688K	0.996
4:153704971:T:G	N688K	0.996
4:153705026:T:C	F707L	0.996
4:153705028:T:A	F707L	0.996
4:153705028:T:G	F707L	0.996
4:153705043:G:C	W712C	0.996
4:153705043:G:T	W712C	0.996
4:153704937:G:C	R677P	0.995
4:153705152:T:C	F749L	0.995
4:153705154:C:A	F749L	0.995
4:153705154:C:G	F749L	0.995
4:153704943:T:C	F679S	0.994
4:153704993:A:C	S696R	0.994
4:153704995:C:A	S696R	0.994
4:153704995:C:G	S696R	0.994
4:153704207:T:A	W434R	0.993
4:153704207:T:C	W434R	0.993
4:153704849:A:C	S648R	0.993
4:153704851:T:A	S648R	0.993
4:153704851:T:G	S648R	0.993

dbSNP variants (sampled 300 via entrez): RS1000058927 (4:153685403 A>G), RS1000139977 (4:153683897 G>C), RS1000312095 (4:153697182 GT>G,GTT), RS1000315159 (4:153705814 A>G), RS1000506553 (4:153709393 C>G,T), RS1000511814 (4:153684121 G>T), RS1000536734 (4:153707140 G>C), RS10006364 (4:153685038 T>A,G), RS1000681159 (4:153702461 C>T), RS1000851555 (4:153690084 C>T), RS1000962812 (4:153708894 G>C), RS1001095641 (4:153694432 A>G), RS1001189972 (4:153703296 A>G), RS1001196410 (4:153696799 C>T), RS10014851 (4:153701865 G>A)

Disease associations

OMIM: gene MIM:603028 | disease phenotypes: MIM:114500, MIM:246300

GenCC curated gene-disease

Mondo (4): colorectal cancer (MONDO:0005575), COVID-19–associated multisystem inflammatory syndrome in adults (MONDO:0100319), leprosy, susceptibility to, 3 (MONDO:0009518), hereditary angioedema with normal C1Inh (MONDO:0100567)

Orphanet (3): Leprosy (Orphanet:548), Hereditary angioedema with normal C1Inh (Orphanet:528647), NON RARE IN EUROPE: Colorectal cancer (Orphanet:466667)

HPO phenotypes

9 total (9 of 9 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001442	Typified by somatic mosaicism
HP:0002715	Abnormality of the immune system
HP:0002891	Uterine leiomyosarcoma
HP:0003003	Colon cancer
HP:0005584	Renal cell carcinoma
HP:0006716	Hereditary nonpolyposis colorectal carcinoma
HP:0006740	Transitional cell carcinoma of the bladder
HP:0006753	Neoplasm of the stomach

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008157_29	Body fat mass	9.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL3301399 (PROTEIN COMPLEX), CHEMBL3885643 (PROTEIN COMPLEX), CHEMBL4163 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

6 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs11938228	Efficacy	3	Tumor necrosis factor alpha (TNF-alpha) inhibitors	Inflammatory Bowel Diseases;Psoriasis
rs1816702	Efficacy	3	Tumor necrosis factor alpha (TNF-alpha) inhibitors	Crohn Disease
rs3804099	Efficacy	3	Tumor necrosis factor alpha (TNF-alpha) inhibitors	Inflammatory Bowel Diseases
rs3804100	Dosage	3	morphine	Pain;Postoperative
rs4696480	Efficacy	3	Tumor necrosis factor alpha (TNF-alpha) inhibitors	Ulcerative Colitis
rs4696480	Efficacy	3	Tumor necrosis factor alpha (TNF-alpha) inhibitors	Psoriasis

PharmGKB variants

5 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1816702	TLR2	3	2.75	1	Tumor necrosis factor alpha (TNF-alpha) inhibitors
rs3804099	TLR2	3	3.00	1	Tumor necrosis factor alpha (TNF-alpha) inhibitors
rs4696480	TLR2	3	3.25	2	Tumor necrosis factor alpha (TNF-alpha) inhibitors
rs11938228	TLR2	3	6.50	1	Tumor necrosis factor alpha (TNF-alpha) inhibitors
rs3804100	TLR2	3	2.50	1	morphine

GtoPdb / IUPHAR curated pharmacology

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

Target class: catalytic receptor — Toll-like receptor family

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
diprovocim-1	Agonist	9.96	pEC50
compound 13 [PMID: 23098072]	Agonist	7.6	pKi
tomaralimab	Binding	7.54	pKd

Binding affinities (BindingDB)

32 measured of 32 human assays (32 total across all organisms); most potent 32 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
methyl (2S)-2-[[(2R)-2-acetamido-3-[2-(hexadecoxycarbonylamino)ethylsulfanyl]propanoyl]amino]-3-hydroxypropanoate	EC50	61.5 nM	US-9676818: Toll-like receptor 2-agonistic lipopeptides, and method of making the same
2-[(2R)-2-acetamido-3-[[(2S)-3-hydroxy-1-methoxy-1-oxopropan-2-yl]amino]-3-oxopropyl]sulfanylethyl (3R)-3-acetyloxytetradecanoate	EC50	182 nM	US-9676818: Toll-like receptor 2-agonistic lipopeptides, and method of making the same
2-[(2R)-2-acetamido-3-[[(2S)-6-amino-1-methoxy-1-oxohexan-2-yl]amino]-3-oxopropyl]sulfanylethyl hexadecanoate	EC50	225 nM	US-9676818: Toll-like receptor 2-agonistic lipopeptides, and method of making the same
hexadecyl N-[2-[(2R)-2-acetamido-3-[[(2S)-1-[3-(dimethylamino)propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-oxopropyl]sulfanylethyl]carbamate	EC50	279 nM	US-9676818: Toll-like receptor 2-agonistic lipopeptides, and method of making the same
methyl (2S)-2-[[(2R)-2-acetamido-3-[2-(hexadecylcarbamoyloxy)ethylsulfanyl]propanoyl]amino]-3-hydroxypropanoate	EC50	323 nM	US-9676818: Toll-like receptor 2-agonistic lipopeptides, and method of making the same
2-[(2R)-2-acetamido-3-[[(2S)-3-hydroxy-1-methoxy-1-oxopropan-2-yl]amino]-3-oxopropyl]sulfanylethyl (3R)-3-butanoyloxytetradecanoate	EC50	345 nM	US-9676818: Toll-like receptor 2-agonistic lipopeptides, and method of making the same
4-[(2S)-2-[[(2R)-2-acetamido-3-(2-hexadecanoyloxyethylsulfanyl)propanoyl]amino]-3-methoxy-3-oxopropoxy]-4-oxobutanoic acid	EC50	518 nM	US-9676818: Toll-like receptor 2-agonistic lipopeptides, and method of making the same
2-[(2R)-2-acetamido-3-[[(2S)-3-hydroxy-1-methoxy-1-oxopropan-2-yl]amino]-3-oxopropyl]sulfanylethyl (3R)-3-formyloxytetradecanoate	EC50	808 nM	US-9676818: Toll-like receptor 2-agonistic lipopeptides, and method of making the same
2-[(2R)-2-acetamido-3-[[(2S)-3-hydroxy-1-methoxy-1-oxopropan-2-yl]amino]-3-oxopropyl]sulfanylethyl hexadecanoate	EC50	1010 nM	US-9676818: Toll-like receptor 2-agonistic lipopeptides, and method of making the same
2-[(2R)-2-acetamido-3-[[(2S)-3-hydroxy-1-methoxy-1-oxopropan-2-yl]amino]-3-oxopropyl]sulfanylethyl (3R)-3-hydroxytetradecanoate	EC50	1130 nM	US-9676818: Toll-like receptor 2-agonistic lipopeptides, and method of making the same
[(2S)-2-[[(2R)-2-acetamido-3-(2-hexadecanoyloxyethylsulfanyl)propanoyl]amino]-3-methoxy-3-oxopropyl] pyridine-3-carboxylate	EC50	1270 nM	US-9676818: Toll-like receptor 2-agonistic lipopeptides, and method of making the same
2-[(2R)-2-acetamido-3-[[(2S)-3-hydroxy-1-methoxy-1-oxopropan-2-yl]amino]-3-oxopropyl]sulfanylethyl (3R)-3-hexanoyloxytetradecanoate	EC50	1500 nM	US-9676818: Toll-like receptor 2-agonistic lipopeptides, and method of making the same
2-[(2R)-2-(butanoylamino)-3-[[(2S)-3-hydroxy-1-methoxy-1-oxopropan-2-yl]amino]-3-oxopropyl]sulfanylethyl hexadecanoate	EC50	1640 nM	US-9676818: Toll-like receptor 2-agonistic lipopeptides, and method of making the same
2-[(2R)-3-[[(2S)-3-acetyloxy-1-methoxy-1-oxopropan-2-yl]amino]-2-amino-3-oxopropyl]sulfanylethyl hexadecanoate	EC50	2970 nM	US-9676818: Toll-like receptor 2-agonistic lipopeptides, and method of making the same
2-[(2R)-2-acetamido-3-[[(2S)-3-hydroxy-1-methoxy-1-oxopropan-2-yl]amino]-3-oxopropyl]sulfanylethyl (3R)-3-octanoyloxytetradecanoate	EC50	3080 nM	US-9676818: Toll-like receptor 2-agonistic lipopeptides, and method of making the same
2-[(2R)-2-amino-3-[[(2S)-3-hydroxy-1-methoxy-1-oxopropan-2-yl]amino]-3-oxopropyl]sulfanylethyl hexadecanoate	EC50	3630 nM	US-9676818: Toll-like receptor 2-agonistic lipopeptides, and method of making the same
2-[(2R)-3-[[(2S)-3-hydroxy-1-methoxy-1-oxopropan-2-yl]amino]-2-(octanoylamino)-3-oxopropyl]sulfanylethyl hexadecanoate	EC50	3800 nM	US-9676818: Toll-like receptor 2-agonistic lipopeptides, and method of making the same
2-[(2R)-3-[[(2S)-3-hydroxy-1-methoxy-1-oxopropan-2-yl]amino]-3-oxo-2-[(2,2,2-trifluoroacetyl)amino]propyl]sulfanylethyl hexadecanoate	EC50	4450 nM	US-9676818: Toll-like receptor 2-agonistic lipopeptides, and method of making the same
[(3R)-1-[2-[(2R)-2-acetamido-3-[[(2S)-3-hydroxy-1-methoxy-1-oxopropan-2-yl]amino]-3-oxopropyl]sulfanylethoxy]-1-oxotetradecan-3-yl] hexadecanoate	EC50	4780 nM	US-9676818: Toll-like receptor 2-agonistic lipopeptides, and method of making the same
2-[(2R)-2-amino-3-[[(2S)-3-hydroxy-1-methoxy-1-oxopropan-2-yl]amino]-3-oxopropyl]sulfanylethyl octadecanoate	EC50	4790 nM	US-9676818: Toll-like receptor 2-agonistic lipopeptides, and method of making the same
2-[(2R)-2-amino-3-[[(2S)-3-butanoyloxy-1-methoxy-1-oxopropan-2-yl]amino]-3-oxopropyl]sulfanylethyl hexadecanoate	EC50	5470 nM	US-9676818: Toll-like receptor 2-agonistic lipopeptides, and method of making the same
3-[(2R)-2-acetamido-3-[[(2S)-3-hydroxy-1-methoxy-1-oxopropan-2-yl]amino]-3-oxopropyl]sulfanylpropyl hexadecanoate	EC50	5520 nM	US-9676818: Toll-like receptor 2-agonistic lipopeptides, and method of making the same
2-[(2R)-2-amino-3-[[(2S)-3-hexadecanoyloxy-1-methoxy-1-oxopropan-2-yl]amino]-3-oxopropyl]sulfanylethyl hexadecanoate	EC50	5950 nM	US-9676818: Toll-like receptor 2-agonistic lipopeptides, and method of making the same
2-[(2R)-2-acetamido-3-[[(2S)-3-[(2S)-2,3-diaminopropanoyl]oxy-1-methoxy-1-oxopropan-2-yl]amino]-3-oxopropyl]sulfanylethyl hexadecanoate	EC50	6810 nM	US-9676818: Toll-like receptor 2-agonistic lipopeptides, and method of making the same
2-[(2R)-2-acetamido-3-[[(2S)-1-methoxy-1-oxo-3-sulfooxypropan-2-yl]amino]-3-oxopropyl]sulfanylethyl hexadecanoate	EC50	7100 nM	US-9676818: Toll-like receptor 2-agonistic lipopeptides, and method of making the same
2-[(2R)-2-acetamido-3-[[(2S)-3-hydroxy-1-methoxy-1-oxopropan-2-yl]amino]-3-oxopropyl]sulfanylethyl (3R)-3-tetradecanoyloxytetradecanoate	EC50	9520 nM	US-9676818: Toll-like receptor 2-agonistic lipopeptides, and method of making the same
methyl (2S)-2-[[(2R)-2-acetamido-3-[2-(hexadecanoylamino)ethylsulfanyl]propanoyl]amino]-3-hydroxypropanoate	EC50	11800 nM	US-9676818: Toll-like receptor 2-agonistic lipopeptides, and method of making the same
2-[(2R)-2-acetamido-3-[[(2S)-3-hydroxy-1-methoxy-1-oxopropan-2-yl]amino]-3-oxopropyl]sulfanylethyl (3R)-3-decanoyloxytetradecanoate	EC50	12900 nM	US-9676818: Toll-like receptor 2-agonistic lipopeptides, and method of making the same
2-[(2R)-2-acetamido-3-[[(2S)-3-hydroxy-1-methoxy-1-oxopropan-2-yl]amino]-3-oxopropyl]sulfanylethyl (3R)-3-dodecanoyloxytetradecanoate	EC50	20700 nM	US-9676818: Toll-like receptor 2-agonistic lipopeptides, and method of making the same
hexadecyl N-[2-[(2R)-2-acetamido-3-[[(2S)-1-[[4-[(4-amino-2-butylimidazo[4,5-c]quinolin-1-yl)methyl]phenyl]methylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-oxopropyl]sulfanylethyl]carbamate	EC50	221000 nM	US-9676818: Toll-like receptor 2-agonistic lipopeptides, and method of making the same
methyl (2S)-2-[[(2R)-2-acetamido-3-[2-(4-tridecyltriazol-1-yl)ethylsulfanyl]propanoyl]amino]-3-hydroxypropanoate	EC50	260000 nM	US-9676818: Toll-like receptor 2-agonistic lipopeptides, and method of making the same
methyl (2S)-2-[[(2R)-2-acetamido-3-[2-(1-hexadecyltriazol-4-yl)ethylsulfanyl]propanoyl]amino]-3-hydroxypropanoate	EC50	641000 nM	US-9676818: Toll-like receptor 2-agonistic lipopeptides, and method of making the same

ChEMBL bioactivities

499 potent at pChembl≥5 of 547 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
9.94	EC50	0.116	nM	CHEMBL5575324
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
9.59	EC50	0.26	nM	CHEMBL1923557
9.57	EC50	0.27	nM	CHEMBL5180856
9.55	EC50	0.281	nM	CHEMBL4552043
9.55	EC50	0.28	nM	CHEMBL4756806
9.55	EC50	0.28	nM	CHEMBL5269670
9.54	EC50	0.29	nM	CHEMBL5208333
9.52	EC50	0.304	nM	CHEMBL4442356
9.52	EC50	0.3	nM	CHEMBL4759425
9.52	EC50	0.3	nM	CHEMBL2179400
9.52	EC50	0.3	nM	CHEMBL5205549
9.49	EC50	0.32	nM	CHEMBL5205005

PubChem BioAssay actives

463 with measured affinity, of 1532 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
[(2S)-3-[(2R,3R,4R,5R)-5-[(2R,4R)-2-dodecyl-1,3-dioxolan-4-yl]-3,4-dihydroxyoxolan-2-yl]oxy-2-hydroxypropyl] dodecanoate	2110085: Agonist activity at TLR2 in PMA-differentiated human THP-1 cells assessed as increase in TNF-alpha level by ELISA	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
(2S)-2-[[(2S)-5-amino-2-[[(2S,3R)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2R)-2-amino-3-[(2R)-2,6-di(hexadecanoyloxy)hexyl]sulfanylpropanoyl]amino]-3-hydroxypropanoyl]amino]hexanoyl]amino]hexanoyl]amino]hexanoyl]amino]hexanoyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-3-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-5-oxopentanoyl]amino]-3-methylbutanoic acid	1604039: Agonist activity at human TLR2 expressed in HEK-Blue cells co-expressing NF-kappaB-SEAP reporter gene measured after 16 hrs by SEAP reporter gene assay	ec50	0.0003	uM
(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-acetamido-3-[(2R)-2,3-di(hexadecanoyloxy)propyl]sulfanylpropanoyl]amino]-3-hydroxypropanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-3-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-5-amino-5-oxopentanoyl]amino]-3-methylbutanoic acid	1604039: Agonist activity at human TLR2 expressed in HEK-Blue cells co-expressing NF-kappaB-SEAP reporter gene measured after 16 hrs by SEAP reporter gene assay	ec50	0.0003	uM
(2S)-2-[[(2S)-2-[[(2R,3R)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-acetamido-3-[(2R)-2,3-di(hexadecanoyloxy)propyl]sulfanylpropanoyl]amino]-3-hydroxypropanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentyl]amino]-4-methylsulfanylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-3-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-5-amino-5-oxopentanoyl]amino]-3-methylbutanoic acid	1692753: Agonist activity at TLR2 (unknown origin)	ec50	0.0003	uM
(2S)-2-[[(2S)-5-amino-2-[[(2R,3R)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2R)-2-amino-3-[(2R)-2,6-di(hexadecanoyloxy)hexyl]sulfanylpropanoyl]amino]-3-hydroxypropanoyl]amino]hexanoyl]amino]hexanoyl]amino]hexanoyl]amino]hexanoyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentyl]amino]-4-methylsulfanylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-3-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-5-oxopentanoyl]amino]-3-methylbutanoic acid	1692753: Agonist activity at TLR2 (unknown origin)	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-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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	affects expression, decreases expression, decreases reaction, increases expression	10
Lipopolysaccharides	increases reaction, decreases reaction, increases expression, decreases expression, affects binding (+2 more)	9
Particulate Matter	affects reaction, increases secretion, increases expression, decreases reaction, decreases expression (+3 more)	8
Estradiol	increases expression, affects cotreatment	5
Methotrexate	affects binding, decreases expression, increases expression	4
Resveratrol	decreases secretion, increases secretion, decreases reaction, increases expression, decreases activity (+1 more)	3
sodium arsenite	decreases expression, increases expression	2
lipopolysaccharide, E. coli O26-B6	increases expression, decreases expression, decreases reaction	2
FSL-1 lipoprotein, synthetic	affects localization, affects reaction, increases expression, increases secretion, affects binding (+2 more)	2
Air Pollutants	affects cotreatment, increases abundance, increases expression	2
Vehicle Emissions	increases abundance, increases expression, decreases expression	2
Benzene	increases expression	2
Diclofenac	decreases expression, increases expression	2
Silicon Dioxide	increases expression, affects reaction, increases secretion	2
Cyclosporine	increases expression	2
Asbestos, Crocidolite	increases expression	2
Simvastatin	decreases reaction, increases expression	2
Nanotubes, Carbon	increases secretion, increases reaction, increases activity, decreases reaction	2
CU-CPT22	decreases reaction, increases expression, decreases expression	1
tungsten carbide	affects cotreatment, decreases expression	1
2-anisidine	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
2,2,2-trichloroethanol	affects cotreatment, increases expression	1
bisphenol A	decreases expression	1
alfacalcidol	decreases expression	1
methylselenic acid	increases expression	1
lipoteichoic acid	increases activity	1
ethyl-p-hydroxybenzoate	increases expression	1
terbufos	increases methylation	1

ChEMBL screening assays

225 unique, capped per target: 202 binding, 23 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3269775	Binding	Agonist activity at human recombinant TLR2/6 expressed in HEK293 cells at 10 uM by SEAP reporter assay	Euodenine A: a small-molecule agonist of human TLR4. — J Med Chem
CHEMBL1839616	Functional	Agonist activity at TLR2 expressed in HEK293 cells co-expressing pNF-kappaB-Luc Cis assessed as NF-kappaB activation at 100 nM by luciferase reporter gene assay	Simple synthetic toll-like receptor 2 ligands. — Bioorg Med Chem Lett

Cellosaurus cell lines

23 cell lines: 14 transformed cell line, 7 cancer cell line, 1 embryonic stem cell, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A8AW	THP1-Dual KO-TLR2	Cancer cell line	Male
CVCL_A8CR	HEK-Blue-Lucia hTLR2 (NF/IL8)	Transformed cell line	Female
CVCL_A8RB	WAe001-A-64	Embryonic stem cell	Male
CVCL_B8QX	Abcam HCT 116 TLR2 KO	Cancer cell line	Male
CVCL_B9TB	Abcam A-549 TLR2 KO	Cancer cell line	Male
CVCL_D6ZX	Leeporter HEK293 TLR2/NF-kB luciferase	Transformed cell line	Female
CVCL_D8CJ	Ubigene A-549 TLR2 KO	Cancer cell line	Male
CVCL_D9UD	Ubigene HEK293 TLR2 KO	Transformed cell line	Female
CVCL_E1DI	Ubigene THP-1 TLR2 KO	Cancer cell line	Male
CVCL_IM79	HEK-TLR2	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00114829	PHASE4	UNKNOWN	Preoperative Assessment of Colon Tumor
NCT00114842	PHASE4	COMPLETED	Magnetic Resonance (MR) Colonography With Fecal Tagging
NCT00114946	PHASE4	TERMINATED	A Study to Compare Two Avastin-Based Treatment Regimens for the Treatment of Metastatic Colorectal Cancer
NCT00122720	PHASE4	COMPLETED	The Effect of Darbepoetin Upon Rehabilitation for Colorectal Cancer Surgery
NCT00129870	PHASE4	TERMINATED	CONCEPT: Comparison of Oxaliplatin vs Conventional Methods With Calcium/Magnesium in First-Line Metastatic Colorectal Cancer
NCT00138060	PHASE4	COMPLETED	Toxicity/Benefit Ratio Optimization of Chemotherapy in Colorectal Cancer (CRC) Patients by Determination of Individual Genotypic Determinants
NCT00216424	PHASE4	TERMINATED	Capecitabine (Xeloda) and Radiation for Patients With Rectosigmoid Carcinoma
NCT00327093	PHASE4	TERMINATED	Elaboration of a Model for Predicting Efficacy of Monoclonal Antibodies (Cetuximab and Bevacizumab) in Patients With Colorectal Cancer and Liver Metastases
NCT00332943	PHASE4	COMPLETED	MR Colonography With Fecal Tagging. Barium vs. BariumFerumoxsil
NCT00441311	PHASE4	COMPLETED	Dissemination of Colorectal Cancer Screening to Primary Care Physicians
NCT00460837	PHASE4	WITHDRAWN	Comparison of Bowel Preparation in Virtual Colonoscopy (VC) - Patient Experience
NCT00473980	PHASE4	COMPLETED	Preoperative Non-steroidal Anti-inflammatory Drugs(NSAID) to Colorectal Cancer Patients
NCT00488904	PHASE4	COMPLETED	Omega-3 Fatty Acids and Postoperative Complications After Colorectal Surgery
NCT00496678	PHASE4	COMPLETED	Trial of Patient Navigation-Activation
NCT00502671	PHASE4	COMPLETED	A Study of Xeloda (Capecitabine) as Adjuvant Monotherapy in Patients With Colon Cancer.
NCT00559676	PHASE4	COMPLETED	Study of Biomarkers in Patients Undergoing Chemotherapy for Metastatic Colorectal Cancer
NCT00577031	PHASE4	COMPLETED	OBELIX Study: A Study of Avastin (Bevacizumab) in Combination With XELOX in Patients With Metastatic Cancer of the Colon or Rectum.
NCT00626054	PHASE4	COMPLETED	Comparison of Two Methods of Administration of a PEG Solution
NCT00812864	PHASE4	COMPLETED	Pharmacokinetic Study of Capecitabine in Elderly Cancer Patient (≥ 75 Years)
NCT00868569	PHASE4	UNKNOWN	Transhepatic Arterial Chemotherapy (TAC) Versus Transcatheter Arterial Chemoembolization (TACE) Plus Folfox4 as the Treatment of Unresectable Liver Metastasis of Colorectal Cancer
NCT00868816	PHASE4	COMPLETED	Oxaliplatine Based Adjuvant Chemotherapy for Stage II/III Colorectal Cancer: 8 Cycles Versus 12 Cycles
NCT00874406	PHASE4	UNKNOWN	Preoperative Transhepatic Arterial Chemotherapy (TAC) in the Treatment of Liver Metastasis of Resectable Colorectal Cancer
NCT00928928	PHASE4	COMPLETED	Oxidative Stress Markers in Open and Laparoscopic Colectomy for Cancer
NCT00942461	PHASE4	COMPLETED	Inflammatory Response in Laparoscopic and Open Colectomy
NCT01023633	PHASE4	UNKNOWN	OPTIMOX1 in Chinese mCRC Patients
NCT01271582	PHASE4	UNKNOWN	Investigation of Association Between UGT1A1 Polymorphisms and Irinotecan Toxicity in Korean Patients
NCT01315990	PHASE4	UNKNOWN	FOLFIRI in Combination With Cetuximab in the First-line Treatment of Metastatic Colorectal Cancer Including a Regular Dermal Prophylaxis to Prevent Acneiforme Follicular Exanthema
NCT01493713	PHASE4	COMPLETED	Correlation Between RECIST, Morphologic Response by CT- Histopathologic Response in Hepatic Metastasis Secondary to Colorectal Cancer
NCT01609660	PHASE4	COMPLETED	Impact of Probiotics on the Intestinal Microbiota
NCT01641458	PHASE4	COMPLETED	Pharmacology-driven Dosing of Fluoropyrimidines in Cancer Patients
NCT01689792	PHASE4	COMPLETED	A Multi-centre Study Comparing the Polyp Detection Rate of Two Different Types of Bowel Preparation: a 2-litre Solution (MOVIPREP®) Versus a Hyperosmotic and Stimulant Combined Low Volume Bowel Preparation (Sodium Picosulfate and Magnesium Citrate)
NCT01695772	PHASE4	COMPLETED	A Study of Bevacizumab Plus 5-Flurouracil (5-FU) Based Doublet Chemotherapy as Neoadjuvant Therapy for Participants With Previously Untreated Unresectable Liver-Only Metastases From Colorectal Cancer
NCT01695863	PHASE4	COMPLETED	Efficacy and Patient Satisfaction of Miralax and Gatorade Versus Movi Prep
NCT01706822	PHASE4	TERMINATED	Radial Reload Laparoscopic LAR Case Series
NCT01740947	PHASE4	TERMINATED	Does Administration of Antibiotics in Patients Undergoing Surgery for Colorectal Cancer Result in Less Complications and Better Prognosis?
NCT01831310	PHASE4	COMPLETED	Nutrition for Colorectal Cancer Patients and Neutrophil Functions
NCT01841294	PHASE4	UNKNOWN	NK Activity Modulation Induced by Intravenous Lidocaine During Colorectal Laparoscopic Surgery
NCT01959061	PHASE4	UNKNOWN	Efficacy and Safety of Raltitrexed-based Transarterial Chemoembolisation(TACE)for Colorectal Cancer Liver Metastases
NCT02032953	PHASE4	UNKNOWN	Enhancing the Anabolic Effect of Perioperative Nutrition With Insulin While Maintaining Normoglycemia
NCT02567331	PHASE4	COMPLETED	A Study of Capecitabine (Xeloda) in Patients With Metastatic Colorectal Cancer