IL17A

Summary

IL17A (interleukin 17A, HGNC:5981) is a protein-coding gene on chromosome 6p12.2, encoding Interleukin-17A (Q16552). Effector cytokine of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity.

This gene is a member of the IL-17 receptor family which includes five members (IL-17RA-E) and the encoded protein is a proinflammatory cytokine produced by activated T cells. IL-17A-mediated downstream pathways induce the production of inflammatory molecules, chemokines, antimicrobial peptides, and remodeling proteins. The encoded protein elicits crucial impacts on host defense, cell trafficking, immune modulation, and tissue repair, with a key role in the induction of innate immune defenses. This cytokine stimulates non-hematopoietic cells and promotes chemokine production thereby attracting myeloid cells to inflammatory sites. This cytokine also regulates the activities of NF-kappaB and mitogen-activated protein kinases and can stimulate the expression of IL6 and cyclooxygenase-2 (PTGS2/COX-2), as well as enhance the production of nitric oxide (NO). IL-17A plays a pivotal role in various infectious diseases, inflammatory and autoimmune disorders, and cancer. High levels of this cytokine are associated with several chronic inflammatory diseases including rheumatoid arthritis, psoriasis and multiple sclerosis. The lung damage induced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is to a large extent, a result of the inflammatory response promoted by cytokines such as IL17A.

Source: NCBI Gene 3605 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 32 total
• Druggable target: yes
• MANE Select transcript: NM_002190

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5981
Approved symbol	IL17A
Name	interleukin 17A
Location	6p12.2
Locus type	gene with protein product
Status	Approved
Aliases	IL-17A, IL-17
Ensembl gene	ENSG00000112115
Ensembl biotype	protein_coding
OMIM	603149
Entrez	3605

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000648244

RefSeq mRNA: 1 — MANE Select: NM_002190 NM_002190

CCDS: CCDS4937

Canonical transcript exons

ENST00000648244 — 3 exons

Exon	Start	End
ENSE00000756110	52187603	52187805
ENSE00001391383	52189055	52190638
ENSE00003839145	52186375	52186458

Expression profiles

Bgee: expression breadth broad, 33 present calls, max score 62.43.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0139 / max 3.9538, expressed in 9 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
68224	0.0139	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endometrium epithelium	UBERON:0004811	62.43	gold quality
paraflocculus	UBERON:0005351	59.90	gold quality
frontal pole	UBERON:0002795	59.53	gold quality
middle frontal gyrus	UBERON:0002702	59.33	gold quality
vermiform appendix	UBERON:0001154	57.72	gold quality
decidua	UBERON:0002450	56.55	gold quality
caecum	UBERON:0001153	53.86	gold quality
pylorus	UBERON:0001166	53.43	silver quality
hair follicle	UBERON:0002073	52.43	gold quality
lower lobe of lung	UBERON:0008949	52.42	silver quality
Brodmann (1909) area 10	UBERON:0013541	51.99	gold quality
cardia of stomach	UBERON:0001162	50.77	gold quality
quadriceps femoris	UBERON:0001377	50.11	gold quality
vastus lateralis	UBERON:0001379	49.73	gold quality
metanephric glomerulus	UBERON:0004736	49.61	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
cerebellar vermis	UBERON:0004720	49.25	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
palpebral conjunctiva	UBERON:0001812	48.56	silver quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
thymus	UBERON:0002370	48.27	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
kidney epithelium	UBERON:0004819	48.11	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-HCAD-29	yes	10521.97
E-ANND-3	no	2.07

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets.

Target	Regulation
KLF15	Repression
KLF2	Unknown
KLF3	Unknown
KRT17	Activation

Upstream regulators (CollecTRI, top): AHR, AP1, BATF, BCL6, CEBPB, CEBPD, CREB1, CREM, CTCF, EGR1, EGR2, ELF4, EOMES, ETV5, EZH2, FOXP3, GFI1, HAND1, HAND2, HDAC11, HIF1A, HIVEP3, HNF1A, IRF1, IRF3, IRF4, JUN, KLF4, NFATC1, NFATC2, NFKB1, NFKB, NFKBIZ, NR1H3, NR2F6, NR3C1, NR4A2, POU2F1, PPARA, PPARD

miRNA regulators (miRDB)

100 targeting IL17A, 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-5692A	100.00	74.40	6850
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488

Literature-anchored findings (GeneRIF, showing 40)

• IL-17 selectively down-regulates TNF-alpha-induced RANTES gene expression in human colonic subepithelial myofibroblasts. (PMID:12165487)
• activation of the ERK pathway is involved in the induction of IL-6 mRNA stabilization by IL-17 plus TNF-alpha. (PMID:12183057)
• IL-17 induces a signaling cascade involving src-MAPK activation in human cells (PMID:12297109)
• IL-17 plays an important role in the induction and perpetuation of the immunopathologic processes in herpetic stromal keratitis by modulating the secretion of proinflammatory and neutrophil chemotactic factors by corneal resident fibroblasts. (PMID:12421973)
• Low levels of IL-17 in combination with IL-1 beta can act on myoblasts and muscle tissue leading to the expression or production of factors involved in muscle inflammation. (PMID:12667656)
• IL-17 may play important role in homeostasis via IL-6 upregulation and in regulating inflammation of prostate (PMID:12772186)
• could have a significant role in the progression of gingivitis to periodontitis (PMID:15025215)
• transcriptional activation of the IL17 gene by Tax protein of HTLV-1 virus. (PMID:15218177)
• upregulation of interleukin 17 is associated with cutaneous T-cell lymphomas (PMID:15305382)
• In Helicobacter pylori-colonized gastric epithelial cells, IL-17-induced IL-8 synthesis is associated with and depends at least in part on the activation of ERK 1/2 MAP kinase. (PMID:15321994)
• IL-17 and IL-17F play a differential regulatory role in GM-CSF production by LMVECs stimulated with IL-1beta and/or TNF-alpha, which is sensitive to Th1 and Th2 cytokine modulation (PMID:15388258)
• NFAT is the crucial sensor of TCR signaling in the IL-17 promoter. (PMID:15459204)
• Review. IL-17 has proinflammatory properties, particularly the induction of other inflammatory effectors. It synergizes with other cytokines, placing it in the center of the inflammatory network. It is implicated in bone diseases & rheumatoid arthritis. (PMID:15535837)
• Review. IL-17 is significant when T cells are a major element of the arthritis process. IL-17 can induce joint destruction in an IL-1-independent manner & can bypass TNF-dependent arthritis. (PMID:15642151)
• has a potential role in the aetiopathogenesis of periodontal disease (PMID:15811054)
• total amount in gingival crevicular fluid samples and in the culture supernatants of gingival cells is significantly increased in periodontal disease (PMID:15811056)
• IL-17 particularly affects post-transcriptional regulation of IL-8 and IL-6 expression leading to enhanced IL-8 and IL-6 responses to secondary stimuli, and is only a weak proinflammatory stimulus by itself (PMID:15845864)
• The fact that the increased IL-17A mRNA is associated with an increased number of MMP-9-expressing neutrophils is compatible with IL-17A increasing the local proteolytic burden through its neutrophil-accumulating effect. (PMID:15916703)
• cell membrane IL-17R is required for signaling by both IL-17A and IL-17F (PMID:15972674)
• IL-17 level is associated with the pathogenesis of early endometriosis and endometriosis-associated infertility. (PMID:16008887)
• The IL-17/IL-8 pathway may be involved in the initial neutrophil influx into the airways in severe asthma. (PMID:16207434)
• Data suggest that IL-17 may play an important role in the inflammatory response to Helicobacter pylori colonization of gastric mucosa. (PMID:16419159)
• In this JEG-3 cell model of human trophoblast, IL-17 may have a regulatory role in trophoblast invasion. (PMID:16533341)
• Inhibitors of MEK abrogated the mitogenic effect of IL-17A, whereas an inhibitor of p38 or JNK displayed no significant inhibitory effect.IL-17A stimulates the growth of airway epithelial cells through the ERK MAP kinase pathway. (PMID:16859642)
• IL-17 may have an important role in the occurrence of nasal polyps by specific combination with IL-17R and over-expression in nasal polyps. (PMID:16874957)
• The data suggest that Th17 cell infiltration in asthmatic airways links T cell activity with neutrophilic inflammation in asthma. (PMID:17083726)
• plays a role as a key regulatory cytokine [in periodontitis] (PMID:17384030)
• human T helper cells-17 cells have distinct migratory capacity and antigenic specificities (PMID:17486092)
• IL-17A can modify epithelial responses to rhinovirus in a manner that would be expected to favor the recruitment of neutrophils, immature dendritic cells, and memory T cells to the airways (PMID:17545490)
• IL-17 is associated with the early post-lung transplantation time period and airway CD8+ cells. (PMID:17613395)
• analysis of functional features of human Th17 cells (PMID:17635957)
• S100A8 is regulated by IL-17, dexamethasone, IL-4 and IL-13 in HaCat cells (human keratinocyte cell line) (PMID:17644317)
• IL-17A activity is an important element of pulmonary host defence, but the prolonged action of this cytokine directed on the proliferation, maturing and chemotaxis of neutrophils to the pulmonary tract may contribute to chronic tissue destruction. (PMID:17682667)
• Our results provided the first evidence that -197A (IL-17A) and 7488T (IL-17F) alleles may influence the susceptibility to and pathophysiological features of ulcerative colitis independently. (PMID:17828618)
• These results provide the first evidence that the IL-17F and MIF gene polymorphisms are significantly associated with the development of functional dyspepsia. (PMID:17912466)
• Data suggest that IL-17-dependent cellular immunity to collagen type V predisposes to obliterative bronchiolitis in human lung transplants. (PMID:17965778)
• two independent and indispensable signaling pathways-1) JAK1-associated PI3K signaling and 2) Act1/TRAF6/TAK1-mediated NF-kappaB activation-are stimulated by IL-17A to regulate gene induction in human airway epithelial cells. (PMID:17982039)
• Il-17 producing T cells are important in mucosal host defense, in the setting of retained antigenic stimulation, such as in asthma, chronic infection, and cystic fibrosis, or in the setting of autoimmunity, these cells can mediate immunopathology [review] (PMID:18075825)
• IL-17A enhances the expression of cyclooxygensase-2 and IL-8 and the proliferation of endometriotic stromal cells. IL-17A may play a role in the development of endometriosis. (PMID:18079209)
• IL-17 gene expression in synovial tissues of Rheumatoid arthritis (RA) was similar to that in Osteoarthritis; expression level in peripheral blood monouclear cells of RA was significantly higher than controls (PMID:18092129)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Il17a	ENSMUSG00000025929
rattus_norvegicus	Il17a	ENSRNOG00000012467
caenorhabditis_elegans		WBGENE00009108

Paralogs (5): IL17F (ENSG00000112116), IL17C (ENSG00000124391), IL17B (ENSG00000127743), IL25 (ENSG00000166090), IL17D (ENSG00000172458)

Protein

Protein identifiers

Interleukin-17A — Q16552 (reviewed: Q16552)

Alternative names: Cytotoxic T-lymphocyte-associated antigen 8

All UniProt accessions (1): Q16552

UniProt curated annotations — full annotation on UniProt →

Function. Effector cytokine of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity. Signals via IL17RA-IL17RC heterodimeric receptor complex, triggering homotypic interaction of IL17RA and IL17RC chains with TRAF3IP2 adapter. This leads to downstream TRAF6-mediated activation of NF-kappa-B and MAPkinase pathways ultimately resulting in transcriptional activation of cytokines, chemokines, antimicrobial peptides and matrix metalloproteinases, with potential strong immune inflammation. Plays an important role in connecting T cell-mediated adaptive immunity and acute inflammatory response to destroy extracellular bacteria and fungi. As a signature effector cytokine of T-helper 17 cells (Th17), primarily induces neutrophil activation and recruitment at infection and inflammatory sites. In airway epithelium, mediates neutrophil chemotaxis via induction of CXCL1 and CXCL5 chemokines. In secondary lymphoid organs, contributes to germinal center formation by regulating the chemotactic response of B cells to CXCL12 and CXCL13, enhancing retention of B cells within the germinal centers, B cell somatic hypermutation rate and selection toward plasma cells. Effector cytokine of a subset of gamma-delta T cells that functions as part of an inflammatory circuit downstream IL1B, TLR2 and IL23A-IL12B to promote neutrophil recruitment for efficient bacterial clearance. Effector cytokine of innate immune cells including invariant natural killer cell (iNKT) and group 3 innate lymphoid cells that mediate initial neutrophilic inflammation. Involved in the maintenance of the integrity of epithelial barriers during homeostasis and pathogen infection. Upon acute injury, has a direct role in epithelial barrier formation by regulating OCLN localization and tight junction biogenesis. As part of the mucosal immune response induced by commensal bacteria, enhances host’s ability to resist pathogenic bacterial and fungal infections by promoting neutrophil recruitment and antimicrobial peptides release. In synergy with IL17F, mediates the production of antimicrobial beta-defensins DEFB1, DEFB103A, and DEFB104A by mucosal epithelial cells, limiting the entry of microbes through the epithelial barriers. Involved in antiviral host defense through various mechanisms. Enhances immunity against West Nile virus by promoting T cell cytotoxicity. May play a beneficial role in influenza A virus (H5N1) infection by enhancing B cell recruitment and immune response in the lung. Contributes to influenza A virus (H1N1) clearance by driving the differentiation of B-1a B cells, providing for production of virus-specific IgM antibodies at first line of host defense.

Subunit / interactions. Homodimer. Forms complexes with IL17RA and IL17RC receptors with 2:1 binding stoichiometry: two receptor chains for one interleukin molecule. IL17A homodimer preferentially drives the formation of IL17RA-IL17RC heterodimeric receptor complex. IL17A homodimer adopts an asymmetrical ternary structure with one IL17RA molecule, allowing for high affinity interactions of one IL17A monomer with one IL17RA molecule (via D1 and D2 domains), while disfavoring binding of a second IL17RA molecule on the other IL17A monomer. Heterodimer with IL17F. IL17A-IL17F forms complexes with IL17RA-IL17RC, but with lower affinity when compared to IL17A homodimer. IL17RA and IL17RC chains cannot distinguish between IL17A and IL17F molecules, potentially enabling the formation of topologically distinct complexes.

Subcellular location. Secreted.

Tissue specificity. Expressed in memory Th17 cells (at protein level).

Post-translational modifications. N-glycosylated. Found both in glycosylated and nonglycosylated forms.

Induction. Induced upon differentiation of CD4-positive T cells. Up-regulated by IL23A-IL12B. Up-regulated in peripheral blood mononuclear cells upon West Nile virus infection.

Similarity. Belongs to the IL-17 family.

RefSeq proteins (1): NP_002181* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010345	IL-17_fam	Family
IPR020440	IL-17_chr	Family
IPR029034	Cystine-knot_cytokine	Homologous_superfamily

Pfam: PF06083

UniProt features (24 total): strand 11, mutagenesis site 5, helix 3, disulfide bond 2, signal peptide 1, chain 1, glycosylation site 1

Structure

Experimental structures (PDB)

44 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9SQX	X-RAY DIFFRACTION	1.41
8USS	X-RAY DIFFRACTION	1.47
9SQI	X-RAY DIFFRACTION	1.48
8DYG	X-RAY DIFFRACTION	1.49
5VB9	X-RAY DIFFRACTION	1.7
5HI4	X-RAY DIFFRACTION	1.8
5HI5	X-RAY DIFFRACTION	1.8
8USR	X-RAY DIFFRACTION	1.83
7Z2M	X-RAY DIFFRACTION	1.9
8DYH	X-RAY DIFFRACTION	1.94
5N7W	X-RAY DIFFRACTION	1.96
9H4O	X-RAY DIFFRACTION	2
8DYF	X-RAY DIFFRACTION	2.02
9FKX	X-RAY DIFFRACTION	2.05
9FL3	X-RAY DIFFRACTION	2.07
9H4D	X-RAY DIFFRACTION	2.12
5HI3	X-RAY DIFFRACTION	2.15
6WIO	X-RAY DIFFRACTION	2.17
4QHU	X-RAY DIFFRACTION	2.2
5HHV	X-RAY DIFFRACTION	2.2
8DY5	X-RAY DIFFRACTION	2.2
8DYI	X-RAY DIFFRACTION	2.28
5N92	X-RAY DIFFRACTION	2.3
4HR9	X-RAY DIFFRACTION	2.48
7AMA	X-RAY DIFFRACTION	2.48
7UWM	ELECTRON MICROSCOPY	2.5
9SR8	X-RAY DIFFRACTION	2.56
9SFX	X-RAY DIFFRACTION	2.6
2VXS	X-RAY DIFFRACTION	2.63
9SG0	X-RAY DIFFRACTION	2.65

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16552-F1	84.60	0.51

Antibody-complex structures (SAbDab): 19 — 2VXS, 4QHU, 5HHV, 5HHX, 5HI3, 5HI4, 5HI5, 5N7W, 6WIO, 6WIR, 7WKX, 7Z2M, 8B7W, 8DY1, 8DY5, 9SFX, 9SG0, 9SG2, 9SGH

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 (2): 94–144, 99–146

Glycosylation sites (1): 68

Mutagenesis-validated functional residues (5):

Position	Phenotype
69	impairs binding to il17ra and il17rc.
78	decreases the affinity for il17ra by 5-fold.
90	has no effect on the affinity for il17ra.
108	decreases the affinity for il17ra.
109	decreases the affinity for il17ra.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-448424	Interleukin-17 signaling
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling
R-HSA-9705671	SARS-CoV-2 activates/modulates innate and adaptive immune responses

MSigDB gene sets: 301 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_DIGESTION, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_OSTEOCLAST_DIFFERENTIATION, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, GOBP_MYELOID_LEUKOCYTE_MIGRATION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_KERATINOCYTE_PROLIFERATION, MODULE_64, GOBP_APICAL_JUNCTION_ASSEMBLY, GOCC_CELL_SURFACE, DARWICHE_SKIN_TUMOR_PROMOTER_DN

GO Biological Process (41): positive regulation of antimicrobial peptide production (GO:0002225), adaptive immune response (GO:0002250), apoptotic process (GO:0006915), inflammatory response (GO:0006954), immune response (GO:0006955), Notch signaling pathway (GO:0007219), cell-cell signaling (GO:0007267), cell death (GO:0008219), response to wounding (GO:0009611), gene expression (GO:0010467), keratinocyte differentiation (GO:0030216), positive regulation of interleukin-1 beta production (GO:0032731), positive regulation of interleukin-12 production (GO:0032735), positive regulation of interleukin-16 production (GO:0032739), positive regulation of interleukin-23 production (GO:0032747), positive regulation of interleukin-6 production (GO:0032755), positive regulation of tumor necrosis factor production (GO:0032760), interleukin-17A-mediated signaling pathway (GO:0038173), keratinocyte proliferation (GO:0043616), innate immune response (GO:0045087), positive regulation of osteoclast differentiation (GO:0045672), positive regulation of transcription by RNA polymerase II (GO:0045944), mRNA stabilization (GO:0048255), defense response to Gram-negative bacterium (GO:0050829), defense response to Gram-positive bacterium (GO:0050830), defense response to fungus (GO:0050832), intestinal epithelial structure maintenance (GO:0060729), cellular response to interleukin-1 (GO:0071347), fibroblast activation (GO:0072537), interleukin-17-mediated signaling pathway (GO:0097400), granulocyte migration (GO:0097530), negative regulation of inflammatory response to wounding (GO:0106015), positive regulation of cytokine production involved in inflammatory response (GO:1900017), positive regulation of bicellular tight junction assembly (GO:1903348), positive regulation of chemokine (C-X-C motif) ligand 1 production (GO:2000340), immune system process (GO:0002376), positive regulation of keratinocyte proliferation (GO:0010838), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), regulation of primary metabolic process (GO:0080090), positive regulation of tumor necrosis factor superfamily cytokine production (GO:1903557)

GO Molecular Function (4): cytokine activity (GO:0005125), protein homodimerization activity (GO:0042803), protein heterodimerization activity (GO:0046982), protein binding (GO:0005515)

GO Cellular Component (3): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), external side of plasma membrane (GO:0009897)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Signaling by Interleukins	2
SARS-CoV-2-host interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of cytokine production	4
immune response	2
protein dimerization activity	2
positive regulation of production of molecular mediator of immune response	1
positive regulation of antimicrobial humoral response	1
antimicrobial peptide production	1
regulation of antimicrobial peptide production	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 surface receptor signaling pathway	1
cell communication	1
signaling	1
cellular process	1
response to stress	1
macromolecule biosynthetic process	1
epidermal cell differentiation	1
skin development	1
interleukin-1 beta production	1
regulation of interleukin-1 beta production	1
positive regulation of interleukin-1 production	1
interleukin-12 production	1
regulation of interleukin-12 production	1
interleukin-16 production	1
regulation of interleukin-16 production	1
interleukin-23 production	1
regulation of interleukin-23 production	1
interleukin-6 production	1
regulation of interleukin-6 production	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
positive regulation of tumor necrosis factor superfamily cytokine production	1
cytokine-mediated signaling pathway	1
epithelial cell proliferation	1
defense response to symbiont	1
receptor ligand activity	1
identical protein binding	1

Protein interactions and networks

STRING

4092 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IL17A	IL17RA	Q96F46	999
IL17A	IL17RC	Q8NAC3	997
IL17A	IFNG	P01579	976
IL17A	CD4	P01730	972
IL17A	IL6	P05231	969
IL17A	IL22	Q9GZX6	967
IL17A	IL10	P22301	966
IL17A	IL1B	P01584	960
IL17A	TNF	P01375	957
IL17A	IL4	P05112	955
IL17A	FOXP3	Q9BZS1	949
IL17A	IL2	P01585	942
IL17A	TBX21	Q9UL17	938
IL17A	CD8A	P01732	937
IL17A	IL13	P35225	936

IntAct

16 interactions, top by confidence:

A	B	Type	Score
IL17RA	IL17A	psi-mi:“MI:0407”(direct interaction)	0.810
IL17A	IL17RA	psi-mi:“MI:0407”(direct interaction)	0.810
IL17RA	IL17A	psi-mi:“MI:0915”(physical association)	0.810
IL17A	DPH2	psi-mi:“MI:0915”(physical association)	0.560
DPH2	IL17A	psi-mi:“MI:0915”(physical association)	0.560
IL17A	KCNIP4	psi-mi:“MI:0915”(physical association)	0.560
IL17A	IL2	psi-mi:“MI:0914”(association)	0.530
IL17A	IL17F	psi-mi:“MI:0407”(direct interaction)	0.440
IL17A	IL17RC	psi-mi:“MI:0407”(direct interaction)	0.440
IL17A	ATP1A3	psi-mi:“MI:0914”(association)	0.350
KCNIP4	IL17A	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (22): IL17A (Two-hybrid), ATP1A3 (Affinity Capture-MS), DPP8 (Affinity Capture-MS), LONP2 (Affinity Capture-MS), IL2 (Affinity Capture-MS), IL17RA (Affinity Capture-MS), TXNDC15 (Affinity Capture-MS), IL2 (Affinity Capture-MS), DPP8 (Affinity Capture-MS), LONP2 (Affinity Capture-MS), TXNDC15 (Affinity Capture-MS), IL17RA (Affinity Capture-MS), KCNIP4 (Two-hybrid), ATP1A3 (Affinity Capture-MS), TXNDC15 (Affinity Capture-MS)

ESM2 similar proteins: A6N6I9, B0VXV3, B0VXV4, C0K3N1, O40633, O46526, P00683, P0DW98, P24916, P34129, P49764, P50412, P67861, P67862, P67863, Q16552, Q330K6, Q3HRV3, Q3S2X5, Q5BJ95, Q60I29, Q61453, Q62386, Q63434, Q687Y7, Q6J936, Q7TNI7, Q8K4C5, Q8SPN3, Q8SPN4, Q8VD87, Q8VHH8, Q90X23, Q90X24, Q96PD4, Q9D244, Q9P0M4, Q9QXT6, Q9QYX2, Q9QYX3

Diamond homologs: A6N6I9, O40633, P24916, Q16552, Q5BJ95, Q60I29, Q61453, Q62386, Q687Y7, Q7TNI7, Q8TAD2, Q96PD4, Q9EQI6, Q9QXT6, Q9UHF5, A9XE49, Q8K4C5, Q8VHH8, Q9H293, Q9P0M4

SIGNOR signaling

13 interactions.

A	Effect	B	Mechanism
IL17A	“down-regulates quantity by repression”	KLF15	“transcriptional regulation”
IL17A	“up-regulates quantity by expression”	KLF2	“transcriptional regulation”
IL17A	“up-regulates quantity by expression”	KLF3	“transcriptional regulation”
IL17A	up-regulates	KLF2	“transcriptional regulation”
IL17A	up-regulates	KLF3	“transcriptional regulation”
SMAD2/STAT3/EP300	up-regulates	IL17A	“transcriptional regulation”
RORC	up-regulates	IL17A	“transcriptional regulation”
IL17A	“up-regulates quantity by expression”	KRT17	“transcriptional regulation”
IL17A	“up-regulates activity”	“IL17R complex”	binding
T_cell_activation	“up-regulates quantity”	IL17A
“Secukinumab (Cosentyx)”	“down-regulates activity”	IL17A	binding
IL17A	up-regulates	IL17RA	binding
NFKBIZ	“up-regulates quantity by expression”	IL17A	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	24
Likely benign	1
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

356 predictions. Top by Δscore:

Variant	Effect	Δscore
6:52187591:A:AG	acceptor_gain	1.0000
6:52187592:T:G	acceptor_gain	1.0000
6:52187595:A:AG	acceptor_gain	1.0000
6:52187596:A:G	acceptor_gain	1.0000
6:52187597:TTCTA:T	acceptor_loss	1.0000
6:52187598:TCTA:T	acceptor_loss	1.0000
6:52187599:CTAGT:C	acceptor_loss	1.0000
6:52187600:TAGTC:T	acceptor_loss	1.0000
6:52187601:A:AG	acceptor_gain	1.0000
6:52187601:A:AT	acceptor_loss	1.0000
6:52187602:G:GT	acceptor_gain	1.0000
6:52187602:GT:G	acceptor_gain	1.0000
6:52187602:GTC:G	acceptor_gain	1.0000
6:52187602:GTCA:G	acceptor_gain	1.0000
6:52187602:GTCAC:G	acceptor_gain	1.0000
6:52187802:TCCA:T	donor_gain	1.0000
6:52187806:G:GG	donor_gain	1.0000
6:52187823:A:G	donor_gain	1.0000
6:52189053:A:AG	acceptor_gain	1.0000
6:52189054:G:GG	acceptor_gain	1.0000
6:52189054:GCC:G	acceptor_gain	1.0000
6:52186456:GTG:G	donor_gain	0.9900
6:52186456:GTGGT:G	donor_loss	0.9900
6:52186457:TGG:T	donor_loss	0.9900
6:52186458:GGTGA:G	donor_loss	0.9900
6:52186459:G:GG	donor_gain	0.9900
6:52186459:GTG:G	donor_loss	0.9900
6:52186460:T:A	donor_loss	0.9900
6:52186461:G:GT	donor_loss	0.9900
6:52187597:T:G	acceptor_gain	0.9900

AlphaMissense

1000 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:52189119:T:A	C99S	0.997
6:52189120:G:C	C99S	0.997
6:52187797:G:C	W74C	0.996
6:52187797:G:T	W74C	0.996
6:52189104:T:A	C94S	0.996
6:52189105:G:C	C94S	0.996
6:52189254:T:A	C144S	0.996
6:52189255:G:C	C144S	0.996
6:52189261:G:A	C146Y	0.994
6:52187781:G:C	R69P	0.992
6:52187795:T:A	W74R	0.992
6:52187795:T:C	W74R	0.992
6:52189104:T:C	C94R	0.992
6:52189119:T:C	C99R	0.992
6:52189254:T:C	C144R	0.992
6:52189260:T:A	C146S	0.992
6:52189260:T:C	C146R	0.992
6:52189261:G:C	C146S	0.992
6:52189262:T:G	C146W	0.991
6:52189080:C:T	P86S	0.990
6:52189261:G:T	C146F	0.990
6:52189106:C:G	C94W	0.988
6:52189174:A:C	Q117P	0.988
6:52189120:G:A	C99Y	0.987
6:52189121:C:G	C99W	0.987
6:52189186:T:A	V121D	0.987
6:52189076:A:C	R84S	0.986
6:52189076:A:T	R84S	0.986
6:52189081:C:A	P86H	0.986
6:52189256:C:G	C144W	0.985

dbSNP variants (sampled 300 via entrez): RS1000402748 (6:52187484 C>T), RS1000879143 (6:52190780 C>T), RS1001348709 (6:52184951 C>A,G), RS1001565921 (6:52187337 C>T), RS1001598373 (6:52187138 T>C), RS1002408474 (6:52190614 T>C), RS1002418298 (6:52190996 T>G), RS1003192314 (6:52184487 G>A,C,T), RS1003330121 (6:52186061 C>T), RS1003349859 (6:52185558 G>A,T), RS1003687468 (6:52185805 T>A), RS1004280028 (6:52187144 G>C,T), RS1004766444 (6:52185632 T>A), RS1004921067 (6:52190071 T>C), RS1005303629 (6:52188869 T>A)

Disease associations

OMIM: gene MIM:603149 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008163_401	Height	2.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3390822 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2275913	Efficacy	3	Tumor necrosis factor alpha (TNF-alpha) inhibitors	Inflammatory Bowel Diseases;Ulcerative Colitis
rs2275913	Dosage	3	opioids	Pain;Postoperative

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2275913	IL17A	3	2.75	2	opioids;Tumor necrosis factor alpha (TNF-alpha) inhibitors
rs3819024	IL17A		0.00	0

Binding affinities (BindingDB)

287 measured of 315 human assays (315 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
5-cyano-N-((1S)-1- cyclohexyl-2-((2- (methylcarbamoyl)-2- (6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrrole-2-carboxamide	IC50	5.5 nM	US-20250154138: Small Molecule IL-17A Modulators
N-(1-(4- ethylcyclohexyl)-2-((2- (methylcarbamoyl)-2- (7-oxo-6,8- diazaspiro[3.5]nonan-6- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	5.6 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cyclohexyl- 2-((2- (methylcarbamoyl)-2- (7-oxo-6,8- diazaspiro[3.5]nonan-6- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	5.8 nM	US-20250154138: Small Molecule IL-17A Modulators
N-(1-(6-chloro-1,2,3,4- tetrahydronaphthalen-2- yl)-2-((2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	6.3 nM	US-20250154138: Small Molecule IL-17A Modulators
N-(1-(5-chloro-1,2,3,4- tetrahydronaphthalen-2- yl)-2-((2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	6.5 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-((1r,4S)-4- ethylcyclohexyl)-2-((2- (methylcarbamoyl)-2- (6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	7 nM	US-20250154138: Small Molecule IL-17A Modulators
N-(1-(4- ethylcyclohexyl)-2-((2- ((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	7.5 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cyclohexyl- 2-((2- (methylcarbamoyl)-2- (6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	9.5 nM	US-20250154138: Small Molecule IL-17A Modulators
N-(1-(4- isopropylcyclohexyl)-2- ((2-(methylcarbamoyl)- 2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	10 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cyclohexyl- 2-((2-(((R)-1- cyclohexyl-2- hydroxyethyl)carbamoyl)- 2-((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	10 nM	US-20250154138: Small Molecule IL-17A Modulators
N-(1-(4- ethylcyclohexyl)-2-((2- (methylcarbamoyl)-2- (6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	10 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cyclohexyl-2- ((2-(5-methyl-2-oxo-5- (trifluoromethyl) tetrahydropyrimidin- 1(2H)-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	10.9 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cycloheptyl- 2-((2-((R)-4-isopropyl- 2-oxoimidazolidin-1- yl)-2- (methylcarbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide	IC50	11 nM	US-20250154138: Small Molecule IL-17A Modulators
N-(2-((2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-1-(3- methylcyclohexyl)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	12 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cyclohexyl- 2-((2-(5-ethyl-5-methyl- 2- oxotetrahydropyrimidin- 1(2H)-yl)-2- (methylcarbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide	IC50	15 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cyclohexyl- 2-((2- (methylcarbamoyl)-2- (7-oxo-6,8- diazaspiro[3.5]nonan-6- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-4-methyl- 1,2,5-oxadiazole-3- carboxamide	IC50	15 nM	US-20250154138: Small Molecule IL-17A Modulators
5-((S)-2-cyclohexyl-2- (1-methyl-1H-pyrazole- 5- carboxamido)acetamido)- 2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- indene-2-carboxylic acid	IC50	15.3 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-(4,4- difluorocyclohexyl)-2- oxo-2-((2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2-((pyridazin-3- ylmethyl)carbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)ethyl)-4- methyl-1,2,5- oxadiazole-3- carboxamide	IC50	15.9 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cyclohexyl- 2-((2-(((S)-1- cyclohexyl-2- hydroxyethyl)carbamoyl)- 2-((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	16 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cyclohexyl- 2-((2- (methylcarbamoyl)-2- (6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1- cyclopropyl-1H- pyrazole-5-carboxamide	IC50	16 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((2S)-1,1- dicyclopropyl-3-((2- ((dicyclopropylmethyl) carbamoyl)-2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-3- oxopropan-2-yl)-4- methyl-1,2,5- oxadiazole-3- carboxamide	IC50	16.5 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((2S)-1,1- dicyclopropyl-3-((2- ((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2-((tetrahydrofuran-3- yl)carbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)-3-oxopropan- 2-yl)-4-methyl-1,2,5- oxadiazole-3- carboxamide	IC50	17.3 nM	US-20250154138: Small Molecule IL-17A Modulators
N-(2-((2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-1-(4- methylcyclohexyl)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	18 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((S)-1,1- dicyclopropyl-3-((2- (cyclopropyl((S)-2-oxo- 4- (trifluoromethyl) imidazolidin- 1-yl)-13-methyl)- 2,3-dihydro-213- benzofuran-6- yl)amino)-3-oxopropan- 2-yl)-1-isopropyl-1H- pyrazole-5-carboxamide	IC50	18.6 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cyclohexyl- 2-((2-((R)-4-isopropyl- 2-oxoimidazolidin-1- yl)-2-((pyridin-2- ylmethyl)carbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	19 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((2S)-1,1- dicyclopropyl-3-((2- (methylcarbamoyl)-2- (7-oxo-6,8- diazaspiro[3.5]nonan-6- yl)-2,3-dihydro-1H- inden-5-yl)amino)-3- oxopropan-2-yl)-1- methyl-1H-pyrazole-5- carboxamide	IC50	19 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cyclohexyl- 2-((2- (isobutylcarbamoyl)-2- ((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	19 nM	US-20250154138: Small Molecule IL-17A Modulators
4-cyano-N-((1S)-1- cyclohexyl-2-((2- (methylcarbamoyl)-2- (6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrrole-2-carboxamide	IC50	19 nM	US-20250154138: Small Molecule IL-17A Modulators
N-(1-(7-chloro-1,2,3,4- tetrahydronaphthalen-2- yl)-2-((2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	19.8 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cyclohexyl- 2-((2-((R)-4-isopropyl- 2-oxoimidazolidin-1- yl)-2-((4- methoxybenzyl)carbam oyl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	20 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cyclohexyl- 2-((2-((R)-4-(4- methoxybenzyl)-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	20 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-(4,4- difluorocyclohexyl)-2- ((2-(2-hydroxypropan- 2-yl)-2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-4-methyl- 1,2,5-oxadiazole-3- carboxamide	IC50	20.9 nM	US-20250154138: Small Molecule IL-17A Modulators
5-((S)-2-cyclohexyl-2- (3- methylbenzamido) acetamido)- 2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- N-methyl-2,3-dihydro- 1H-indene-2- carboxamide	IC50	21 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-2-((2- carbamoyl-2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-1- cycloheptyl-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	22 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-2-((2-((1- cyclobutyl-2- hydroxyethyl) carbamoyl)- 2-((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-1- cyclohexyl-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide	IC50	22 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cyclohexyl- 2-((2-((2- fluorobenzyl)carbamoyl)- 2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	22.4 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cyclohexyl- 2-((2- (methylcarbamoyl)-2- (8-oxo-7,9- diazaspiro[4.5]decan-7- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	22.4 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cyclohexyl- 2-((2-((R)-4-isopropyl- 2-oxoimidazolidin-1- yl)-2- (methylcarbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide	IC50	22.6 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((2S)-1,1- dicyclopropyl-3-((2-((3- fluorophenyl)carbamoyl)- 2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-3- oxopropan-2-yl)-4- methyl-1,2,5- oxadiazole-3- carboxamide	IC50	23.3 nM	US-20250154138: Small Molecule IL-17A Modulators
5-((S)-2-benzamido-2- cyclohexylacetamido)- 2-((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- N-methyl-2,3-dihydro- 1H-indene-2- carboxamide	IC50	24 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cyclohexyl- 2-((2-((R)-4-(4- methylbenzyl)-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	24 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((2S)-1,1- dicyclopropyl-3-((2-((2- ethylphenyl)carbamoyl)- 2-((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-3- oxopropan-2-yl)-4- methyl-1,2,5- oxadiazole-3- carboxamide	IC50	24.5 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cyclohexyl- 2-((2-((R)-4-isopropyl- 2-oxoimidazolidin-1- yl)-2- (methylcarbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)-2-oxoethyl)- 4-methyl-1,2,5- oxadiazole-3- carboxamide	IC50	25 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cyclohexyl- 2-((2-((1-cyclopentyl-2- hydroxyethyl)carbamoyl)- 2-((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	25 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cyclohexyl- 2-((2-(5,5-dimethyl-2- oxotetrahydropyrimidin- 1(2H)-yl)-2- (methylcarbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide	IC50	26 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-2-((2- (bicyclo[1.1.1]pentan-1- ylcarbamoyl)-2-(6-oxo- 5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-1- cyclohexyl-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide	IC50	26.9 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cyclohexyl- 2-oxo-2-((2-(((S)-2- oxo-4- (trifluoromethyl) imidazolidin-1-yl) methyl)-2,3- dihydrobenzofuran-6- yl)amino)ethyl)-1- methyl-1H-pyrazole-5- carboxamide	IC50	27.1 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cyclohexyl- 2-((2- (methylcarbamoyl)-2- (6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-ethyl-1H- pyrazole-5-carboxamide	IC50	28 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-(4,4- difluorocyclohexyl)-2- oxo-2-((2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2-(m- tolylcarbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)ethyl)-4- methyl-1,2,5- oxadiazole-3- carboxamide	IC50	28.6 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cyclohexyl- 2-((2-((R)-4-isopropyl- 2-oxoimidazolidin-1- yl)-2-((2,2,2- trifluoroethyl)carbamoyl)- 2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	30 nM	US-20250154138: Small Molecule IL-17A Modulators

ChEMBL bioactivities

55 potent at pChembl≥5 of 57 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.10	IC50	0.7943	nM	CHEMBL5091495
9.00	IC50	1	nM	CHEMBL4870813
8.90	IC50	1.259	nM	CHEMBL5081660
8.90	IC50	1.259	nM	CHEMBL5080633
8.90	IC50	1.259	nM	CHEMBL5091603
8.80	IC50	1.585	nM	CHEMBL5077953
8.80	IC50	1.585	nM	CHEMBL5092697
8.70	IC50	2	nM	CHEMBL4860574
8.70	IC50	2	nM	CHEMBL4865978
8.70	IC50	2	nM	CHEMBL4872143
8.55	IC50	2.8	nM	CHEMBL4845695
8.52	IC50	3	nM	CHEMBL4850368
8.52	IC50	3	nM	CHEMBL4851738
8.34	IC50	4.6	nM	CHEMBL4855085
8.21	Kd	6.2	nM	CHEMBL4869568
8.15	IC50	7	nM	CHEMBL4874078
8.05	IC50	9	nM	CHEMBL5087050
8.00	IC50	10.1	nM	CHEMBL4876088
8.00	IC50	10.1	nM	CHEMBL4866932
7.91	Kd	12.3	nM	CHEMBL4858175
7.89	Kd	12.9	nM	CHEMBL4878993
7.84	IC50	14.3	nM	CHEMBL4860250
7.77	IC50	17	nM	CHEMBL4864604
7.52	Kd	30	nM	CHEMBL5079201
7.50	Kd	32	nM	CHEMBL5194116
7.16	IC50	70	nM	CHEMBL4869568
7.14	Kd	73	nM	CHEMBL5069442
7.05	Kd	89	nM	CHEMBL4854787
6.96	Kd	110	nM	CHEMBL4872876
6.80	IC50	160	nM	CHEMBL5079201
6.77	Kd	170	nM	CHEMBL5177049
6.72	IC50	190	nM	CHEMBL5069442
6.66	IC50	221	nM	CHEMBL5288854
6.51	Kd	309	nM	CHEMBL5177049
6.48	Kd	328	nM	CHEMBL5177049
6.29	Kd	507	nM	CHEMBL5177049
6.26	IC50	550	nM	CHEMBL5748817
6.26	IC50	550	nM	CHEMBL5850355
6.26	IC50	550	nM	CHEMBL5963911
6.26	IC50	550	nM	CHEMBL5763149
6.26	IC50	550	nM	CHEMBL5834488
6.26	IC50	550	nM	CHEMBL4227543
6.26	IC50	550	nM	CHEMBL5814078
6.26	IC50	550	nM	CHEMBL4226731
6.26	IC50	550	nM	CHEMBL6051383
6.26	IC50	550	nM	CHEMBL5998438
6.26	IC50	550	nM	CHEMBL5873751
6.26	IC50	550	nM	CHEMBL5760813
6.26	IC50	550	nM	CHEMBL5845684
6.26	IC50	550	nM	CHEMBL6047338

PubChem BioAssay actives

45 with measured affinity, of 95 total; 34 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
4-cyclopropyl-N-[(S)-(4,4-difluorocyclohexyl)-[5-[(2S)-1-(2,2-difluoropropylamino)-4,4-difluoro-1-oxobutan-2-yl]-4-fluoro-1H-benzimidazol-2-yl]methyl]-1,2,5-oxadiazole-3-carboxamide	1815779: Inhibition of IL-17A in human HDF cells assessed as IL-6 release incubated for 5 hrs by TR-FRET assay	ic50	0.0008	uM
N-[(S)-[5-[(1S)-1-(6-cyano-[1,2,4]triazolo[4,3-a]pyridin-3-yl)-3,3,3-trifluoropropyl]-4-fluoro-1H-benzimidazol-2-yl]-(4,4-difluorocyclohexyl)methyl]-4-methyl-1,2,5-oxadiazole-3-carboxamide	1782624: Inhibition of IL-17A in human HDF cells assessed as IL-6 release incubated for 5 hrs by TR-FRET assay	ic50	0.0010	uM
4-cyclopropyl-N-[(S)-(4,4-difluorocyclohexyl)-[5-[1-(2,2-difluoropropylamino)-4,4-difluoro-1-oxobutan-2-yl]-4-fluoro-1H-benzimidazol-2-yl]methyl]-1,2,5-oxadiazole-3-carboxamide	1815779: Inhibition of IL-17A in human HDF cells assessed as IL-6 release incubated for 5 hrs by TR-FRET assay	ic50	0.0013	uM
N-[(S)-(4,4-difluorocyclohexyl)-[4-fluoro-5-[(2S)-4,4,4-trifluoro-1-[[(2R)-3-methyl-1-(methylamino)-1-oxobutan-2-yl]amino]-1-oxobutan-2-yl]-1H-benzimidazol-2-yl]methyl]-4-methyl-1,2,5-oxadiazole-3-carboxamide	1815779: Inhibition of IL-17A in human HDF cells assessed as IL-6 release incubated for 5 hrs by TR-FRET assay	ic50	0.0013	uM
4-cyclopropyl-N-[(S)-(4,4-difluorocyclohexyl)-[4-fluoro-5-[(2R)-3-methoxy-1-oxo-1-(2,2,2-trifluoroethylamino)propan-2-yl]-1H-benzimidazol-2-yl]methyl]-1,2,5-oxadiazole-3-carboxamide	1815779: Inhibition of IL-17A in human HDF cells assessed as IL-6 release incubated for 5 hrs by TR-FRET assay	ic50	0.0013	uM
N-[(S)-(4,4-difluorocyclohexyl)-[5-[(2S)-4-ethylsulfonyl-1-oxo-1-(3,3,4,4-tetrafluoropyrrolidin-1-yl)butan-2-yl]-4-fluoro-1H-benzimidazol-2-yl]methyl]-4-ethyl-1,2,5-oxadiazole-3-carboxamide	1815779: Inhibition of IL-17A in human HDF cells assessed as IL-6 release incubated for 5 hrs by TR-FRET assay	ic50	0.0016	uM
4-cyclopropyl-N-[(S)-(4,4-difluorocyclohexyl)-[5-[(2S)-1-(2,2-difluoropropylamino)-4,4,4-trifluoro-1-oxobutan-2-yl]-4-fluoro-1H-benzimidazol-2-yl]methyl]-1,2,5-oxadiazole-3-carboxamide	1815779: Inhibition of IL-17A in human HDF cells assessed as IL-6 release incubated for 5 hrs by TR-FRET assay	ic50	0.0016	uM
N-[(S)-(4,4-difluorocyclohexyl)-[5-[(1S)-3,3-difluoro-1-[3-(2,2,2-trifluoroethyl)triazol-4-yl]propyl]-4-fluoro-1H-benzimidazol-2-yl]methyl]-4-methyl-1,2,5-oxadiazole-3-carboxamide	1782624: Inhibition of IL-17A in human HDF cells assessed as IL-6 release incubated for 5 hrs by TR-FRET assay	ic50	0.0020	uM
N-[(S)-(4,4-difluorocyclohexyl)-[5-[(1R)-3,3-difluoro-1-(6-fluoroimidazo[1,2-a]pyridin-3-yl)propyl]-4-fluoro-1H-benzimidazol-2-yl]methyl]-4-methyl-1,2,5-oxadiazole-3-carboxamide	1782624: Inhibition of IL-17A in human HDF cells assessed as IL-6 release incubated for 5 hrs by TR-FRET assay	ic50	0.0020	uM
N-[(S)-(4,4-difluorocyclohexyl)-[4-fluoro-5-[(1S)-3,3,3-trifluoro-1-[3-(2,2,2-trifluoroethyl)triazol-4-yl]propyl]-1H-benzimidazol-2-yl]methyl]-4-methyl-1,2,5-oxadiazole-3-carboxamide	1782624: Inhibition of IL-17A in human HDF cells assessed as IL-6 release incubated for 5 hrs by TR-FRET assay	ic50	0.0020	uM
N-[(S)-(4,4-difluorocyclohexyl)-[7-[(1S)-2-methoxy-1-[(4S)-2-oxo-4-(trifluoromethyl)imidazolidin-1-yl]ethyl]imidazo[1,2-b]pyridazin-2-yl]methyl]-4-(difluoromethyl)-1,2,5-oxadiazole-3-carboxamide	1772145: Inhibition of IL-17A in human HT-29 cells assessed as neutralization measured after 48 hrs by ELISA method	ic50	0.0028	uM
N-[(S)-(4,4-difluorocyclohexyl)-[5-[(1S)-3,3-difluoro-1-(6-fluoro-[1,2,4]triazolo[4,3-a]pyridin-3-yl)propyl]-4-fluoro-1H-benzimidazol-2-yl]methyl]-4-methyl-1,2,5-oxadiazole-3-carboxamide	1782624: Inhibition of IL-17A in human HDF cells assessed as IL-6 release incubated for 5 hrs by TR-FRET assay	ic50	0.0030	uM
N-[(S)-[5-[(1S)-1-(6-cyano-[1,2,4]triazolo[4,3-a]pyrazin-3-yl)-3,3-difluoropropyl]-4-fluoro-1H-benzimidazol-2-yl]-(4,4-difluorocyclohexyl)methyl]-4-methyl-1,2,5-oxadiazole-3-carboxamide	1782624: Inhibition of IL-17A in human HDF cells assessed as IL-6 release incubated for 5 hrs by TR-FRET assay	ic50	0.0030	uM
N-[(S)-(4,4-difluorocyclohexyl)-[7-[(1S)-2-methoxy-1-[(4S)-2-oxo-4-(trifluoromethyl)imidazolidin-1-yl]ethyl]imidazo[1,2-b]pyridazin-2-yl]methyl]-4-(trifluoromethyl)-1,2,5-oxadiazole-3-carboxamide	1772145: Inhibition of IL-17A in human HT-29 cells assessed as neutralization measured after 48 hrs by ELISA method	ic50	0.0046	uM
(2S)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S,3S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S,3S)-2-acetamido-3-methylpentanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-3-methylbutanoyl]amino]-3-hydroxybutanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbonyl]amino]propanoyl]amino]-3-carboxypropanoyl]amino]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-3-carboxypropanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-3-methylpentanoyl]amino]-4-amino-4-oxobutanoyl]amino]-6-aminohexanoic acid	1769193: Binding affinity to biotinylated human IL-17A by SPR analysis	kd	0.0062	uM
3-cyclopropyl-N-[(S)-(4,4-difluorocyclohexyl)-[7-[(1S)-2-methoxy-1-[(4S)-2-oxo-4-(trifluoromethyl)imidazolidin-1-yl]ethyl]imidazo[1,2-b]pyridazin-2-yl]methyl]-1,2-oxazole-4-carboxamide	1772145: Inhibition of IL-17A in human HT-29 cells assessed as neutralization measured after 48 hrs by ELISA method	ic50	0.0070	uM
(20R)-7-chloro-N-methyl-4-[(2-methylpyrazole-3-carbonyl)amino]-3,18-dioxo-2,19-diazatetracyclo[20.2.2.16,10.111,15]octacosa-1(25),6,8,10(28),11,13,15(27),22(26),23-nonaene-20-carboxamide	1811868: Inhibition of IL-17A (unknown origin) measured by FRET assay	ic50	0.0090	uM
4-cyclopropyl-N-[(S)-(4,4-difluorocyclohexyl)-[7-[[(4S)-2-oxo-4-(trifluoromethyl)imidazolidin-1-yl]methyl]imidazo[1,2-b]pyridazin-2-yl]methyl]-1,2,5-oxadiazole-3-carboxamide	1772145: Inhibition of IL-17A in human HT-29 cells assessed as neutralization measured after 48 hrs by ELISA method	ic50	0.0101	uM
N-[(S)-(4,4-difluorocyclohexyl)-[7-[[(4S)-2-oxo-4-(trifluoromethyl)imidazolidin-1-yl]methyl]imidazo[1,2-b]pyridazin-2-yl]methyl]-4-(trifluoromethyl)-1,2,5-oxadiazole-3-carboxamide	1772145: Inhibition of IL-17A in human HT-29 cells assessed as neutralization measured after 48 hrs by ELISA method	ic50	0.0101	uM
(4S)-4-[[(2R)-2-amino-3-sulfanylpropanoyl]amino]-5-[[(2S)-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[(2S)-2-[[(2S)-1-[[(2S)-1-[[(1R)-1-carboxy-2-sulfanylethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-oxopentanoic acid	1769187: Binding affinity to human IL-17A assessed as dissociation constant in PBS-T measured after 60 mins by Biolayer interferometry	kd	0.0123	uM
(4S)-4-[[(2R)-2-amino-3-sulfanylpropanoyl]amino]-5-[[(2S)-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[(2S)-2-[[(2S)-1-[[(2S)-1-[[(1R)-1-carboxy-2-sulfanylethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-oxopentanoic acid	1769187: Binding affinity to human IL-17A assessed as dissociation constant in PBS-T measured after 60 mins by Biolayer interferometry	kd	0.0129	uM
N-[(S)-(4,4-difluorocyclohexyl)-[7-[[(4S)-2-oxo-4-(trifluoromethyl)imidazolidin-1-yl]methyl]imidazo[1,2-b]pyridazin-2-yl]methyl]-4-propan-2-yl-1,2,5-oxadiazole-3-carboxamide	1772145: Inhibition of IL-17A in human HT-29 cells assessed as neutralization measured after 48 hrs by ELISA method	ic50	0.0143	uM
(1R)-2-acetyl-N-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-5-methylsulfonyl-1,3-dihydroisoindole-1-carboxamide	2117427: Inhibition of IL-17A (unknown origin)	ic50	0.0170	uM
(4S)-4-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-carboxypropanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-3-methylbutanoyl]amino]-3-sulfanylpropanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]propanoyl]amino]-3-phenylpropanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-3-carboxypropanoyl]pyrrolidine-2-carbonyl]amino]-5-[[(1R)-1-carboxy-2-sulfanylethyl]amino]-5-oxopentanoic acid	1811867: Binding affinity to IL-17A (unknown origin) measured by SPR assay	kd	0.0300	uM
N-[(2S)-1,1-dicyclopropyl-3-[4-(3,5-dimethyl-1H-pyrazol-4-yl)anilino]-3-oxopropan-2-yl]-2-propan-2-ylpyrazole-3-carboxamide	1881020: Binding affinity to human IL-17A assessed as thermal stability by measuring increase in unfolding temperature by differential scanning fluorimetry	kd	0.0320	uM
(4S)-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-amino-3-sulfanylpropanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-5-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2R)-1-[[(1S)-4-carbamimidamido-1-carboxybutyl]amino]-1-oxo-3-sulfanylpropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	1811867: Binding affinity to IL-17A (unknown origin) measured by SPR assay	kd	0.0730	uM
(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-amino-3-sulfanylpropanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]-3-(4-hydroxyphenyl)propanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-sulfanylpropanoic acid	1769187: Binding affinity to human IL-17A assessed as dissociation constant in PBS-T measured after 60 mins by Biolayer interferometry	kd	0.0890	uM
(2S)-3-(2-chlorophenyl)-2-[(2-phenylacetyl)amino]-N-[4-[[(9R)-7,10,13,21-tetraoxo-8,11,14,20-tetrazaspiro[4.17]docosan-9-yl]methyl]phenyl]propanamide	1811866: Inhibition of IL-17A (unknown origin) by ELISA II	ic50	0.1000	uM
(2S)-3-(2-chlorophenyl)-2-[(2,2-difluoro-2-phenylacetyl)amino]-N-[4-[2-[[2-[1-(2-oxo-2-pyrrolidin-1-ylethyl)cyclopentyl]acetyl]amino]ethyl]phenyl]propanamide	1811866: Inhibition of IL-17A (unknown origin) by ELISA II	ic50	0.1000	uM
(4S)-4-[[(2R)-2-amino-3-sulfanylpropanoyl]amino]-5-[[(2S)-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[(2S)-2-[[(2S)-1-[[(2S)-1-[[(1R)-1-carboxy-2-sulfanylethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	1769187: Binding affinity to human IL-17A assessed as dissociation constant in PBS-T measured after 60 mins by Biolayer interferometry	kd	0.1100	uM
2-[[2-(5-bromo-2-methoxyphenyl)-2-(10,10-dimethyl-8,12-dioxo-1,4-dioxa-7,13-diazacyclopentadec-7-yl)acetyl]amino]-3-phenyl-N-prop-2-enylpropanamide	1871166: Binding affinity at His tagged human IL-17A expressed in Escherichia coli BL21-(DE3) assessed as dissociation constant incubated for 30 mins by MST analysis	kd	0.1700	uM
2-(5-ethylsulfonyl-2-pyridinyl)-N-[(7S)-7-propan-2-yl-6-[[4-(trifluoromethyl)cyclohexyl]methyl]-5,7-dihydropyrrolo[3,4-b]pyridin-3-yl]acetamide	1920975: Inhibition of human IL-17 by whole blood assay	ic50	0.2210	uM
N-[(2S)-1-[4-[2-[[2-[1-[2-(dimethylamino)-2-oxoethyl]cyclopentyl]acetyl]amino]ethyl]anilino]-3-(2-fluorophenyl)-1-oxopropan-2-yl]-2-methylpyrazole-3-carboxamide	1811867: Binding affinity to IL-17A (unknown origin) measured by SPR assay	kd	0.6600	uM
2-[3,5-dimethyl-4-(2-pyrrolidin-1-ylethoxy)phenyl]-5,7-dimethoxy-3H-quinazolin-4-one	1867014: Inhibition of IL-17 in human PBMC	ic50	1.3000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
2-(1’H-indole-3’-carbonyl)thiazole-4-carboxylic acid methyl ester	affects expression, affects secretion	4
Arsenic	affects expression, decreases expression, decreases secretion, increases abundance, increases expression	3
6-formylindolo(3,2-b)carbazole	decreases reaction, increases expression, increases reaction, affects expression, affects cotreatment	2
(+)-JQ1 compound	decreases expression	2
Resveratrol	affects cotreatment, decreases reaction, increases expression, decreases expression	2
Arsenic Trioxide	decreases expression, decreases secretion	2
Air Pollutants	increases abundance, increases expression	2
Lipopolysaccharides	decreases reaction, affects cotreatment, increases expression	2
Ozone	increases abundance, increases expression	2
Simvastatin	decreases expression, decreases secretion, decreases reaction, affects reaction	2
Particulate Matter	decreases expression, increases secretion	2
abemaciclib	increases expression	1
CBP30 compound	decreases expression	1
bisphenol F	affects cotreatment, increases expression	1
NE-52-qq57	increases secretion, decreases reaction, increases expression	1
dihydroouabain	increases expression, increases secretion	1
triptolide	decreases expression	1
bisphenol A	decreases secretion	1
sodium arsenate	increases expression, increases reaction	1
titanium dioxide	affects expression	1
pyrrolidine dithiocarbamic acid	decreases reaction, increases activity, increases expression	1
enterotoxin A, Staphylococcal	increases secretion, affects reaction, decreases reaction, increases expression	1
4-hydroxy-2-nonenal	decreases expression	1
tryptanthrine	affects cotreatment, decreases reaction, increases expression	1
monophosphoryl lipid A	increases secretion	1
LY 215840	decreases expression, decreases reaction	1
SB 203580	decreases reaction, increases expression, increases reaction	1
5-methylindole	affects cotreatment, decreases reaction, increases expression	1
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases reaction, increases expression, increases activity, increases phosphorylation	1
1,25-dihydroxyvitamin D	increases expression	1

ChEMBL screening assays

33 unique, capped per target: 33 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3788850	Binding	Binding affinity to recombinant human IL-17A assessed as protection from deuterium uptake at 58 to 71 residues at 10 uM after 10 to 3600 secs by HDX-MS	A Binding Site on IL-17A for Inhibitory Macrocycles Revealed by Hydrogen/Deuterium Exchange Mass Spectrometry. — J Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8I8	Abcam HCT 116 IL17A KO	Cancer cell line	Male
CVCL_B9KH	Abcam A-549 IL17A KO	Cancer cell line	Male

Clinical trials (associated diseases)

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