S100A9

Summary

S100A9 (S100 calcium binding protein A9, HGNC:10499) is a protein-coding gene on chromosome 1q21.3, encoding Protein S100-A9 (P06702). S100A9 is a calcium- and zinc-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response.

The protein encoded by this gene is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. S100 proteins are localized in the cytoplasm and/or nucleus of a wide range of cells, and involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. S100 genes include at least 13 members which are located as a cluster on chromosome 1q21. This protein may function in the inhibition of casein kinase and altered expression of this protein is associated with the disease cystic fibrosis. This antimicrobial protein exhibits antifungal and antibacterial activity.

Source: NCBI Gene 6280 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 20 total
• Druggable target: yes
• MANE Select transcript: NM_002965

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10499
Approved symbol	S100A9
Name	S100 calcium binding protein A9
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	P14, MIF, NIF, LIAG, MRP14, MAC387, 60B8AG, CGLB, MRP-14, S100-A9
Ensembl gene	ENSG00000163220
Ensembl biotype	protein_coding
OMIM	123886
Entrez	6280

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000368738, ENST00000872632, ENST00000872633, ENST00000872634, ENST00000970306

RefSeq mRNA: 1 — MANE Select: NM_002965 NM_002965

CCDS: CCDS1036

Canonical transcript exons

ENST00000368738 — 3 exons

Exon	Start	End
ENSE00001072566	153357854	153357881
ENSE00001447878	153358269	153358433
ENSE00001512631	153360644	153361023

Expression profiles

Bgee: expression breadth ubiquitous, 244 present calls, max score 99.98.

FANTOM5 (CAGE): breadth broad, TPM avg 198.8973 / max 43100.8644, expressed in 685 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5383	193.9738	678
5386	4.4888	329
5384	0.2728	96
5385	0.1619	74

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.98	gold quality
monocyte	CL:0000576	99.98	gold quality
leukocyte	CL:0000738	99.97	gold quality
mononuclear cell	CL:0000842	99.97	gold quality
bone marrow	UBERON:0002371	99.97	gold quality
periodontal ligament	UBERON:0008266	99.97	gold quality
lower esophagus mucosa	UBERON:0035834	99.97	gold quality
oral cavity	UBERON:0000167	99.96	gold quality
pharyngeal mucosa	UBERON:0000355	99.96	gold quality
gingiva	UBERON:0001828	99.96	gold quality
gingival epithelium	UBERON:0001949	99.95	gold quality
tongue squamous epithelium	UBERON:0006919	99.95	gold quality
bone marrow cell	CL:0002092	99.93	gold quality
trabecular bone tissue	UBERON:0002483	99.93	gold quality
cervix epithelium	UBERON:0004801	99.91	gold quality
esophagus mucosa	UBERON:0002469	99.87	gold quality
body of tongue	UBERON:0011876	99.87	gold quality
blood	UBERON:0000178	99.86	gold quality
palpebral conjunctiva	UBERON:0001812	99.86	gold quality
mammalian vulva	UBERON:0000997	99.84	gold quality
cervix squamous epithelium	UBERON:0006922	99.83	gold quality
right lung	UBERON:0002167	99.81	gold quality
buccal mucosa cell	CL:0002336	99.78	gold quality
spleen	UBERON:0002106	99.70	gold quality
penis	UBERON:0000989	99.69	gold quality
upper lobe of left lung	UBERON:0008952	99.69	gold quality
tongue	UBERON:0001723	99.59	gold quality
squamous epithelium	UBERON:0006914	99.41	gold quality
vagina	UBERON:0000996	99.22	gold quality
upper lobe of lung	UBERON:0008948	99.20	gold quality

Single-cell (SCXA)

Detected in 50 experiment(s), a significant marker in 47.

Experiment	Marker?	Max mean expression
E-HCAD-1	yes	87781.27
E-CURD-112	yes	75982.06
E-GEOD-149689	yes	63803.06
E-MTAB-9221	yes	49550.96
E-HCAD-10	yes	47773.54
E-ANND-2	yes	45192.35
E-MTAB-10432	yes	42465.49
E-MTAB-8207	yes	32408.25
E-MTAB-7407	yes	31944.86
E-GEOD-139324	yes	31204.50
E-HCAD-4	yes	30252.85
E-GEOD-150728	yes	28505.22
E-MTAB-9467	yes	27763.65
E-GEOD-135922	yes	24388.72
E-CURD-55	yes	22030.22

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, CEBPB, CEBPE, CEBPG, GLI1, HIF1A, JDP2, MYB, NFE2L2, NR1H3, PARP1, STAT3, TP53, ZNF316, ZNF335

miRNA regulators (miRDB)

8 targeting S100A9, 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-766-5P	99.47	67.91	2225
HSA-MIR-92A-1-5P	98.28	64.51	631
HSA-MIR-660-3P	98.14	66.04	1434
HSA-MIR-663B	97.40	62.91	664
HSA-MIR-132-5P	96.61	65.79	115
HSA-MIR-4701-5P	96.45	68.41	1121
HSA-MIR-588	96.45	68.36	1127
HSA-MIR-1204	89.50	65.56	109

Literature-anchored findings (GeneRIF, showing 40)

• S100A8/A9 accounts for the entire arachidonic acid-binding capacity of the neutrophil cytosol, indicating that S100A8/A9 plays an essential role in arachidonic acid-dependent enzymes and arachidonic acid-consuming pathways. (PMID:10551823)
• crystal structure of the calcium-bound form, analyzed at 2.1 A resolution (PMID:11851337)
• These data indicate that calprotectin (MRP8 and MRP14) has higher specific activity to induce apoptosis than the individual subunits, and that the mechanism is exclusion of zinc from target cells. (PMID:12137245)
• identifies regulatory elements within the promoter that drive the cell type-specific and differentiation-dependent protein expression (PMID:12167632)
• Proinflammatory myeloid-related protein S100A9 induces a dose- and time-dependent activation of the HIV-1 long terminal repeat promoter region that can be blocked by specific polyclonal antibody and by physical denaturation of the protein. (PMID:12218151)
• S100A8 and S100A9 calcium-binding proteins: localization within normal and cyclosporin A-induced overgrowth gingiva, in spino-cellular layer and extracellularly in desmosomes, in cytoplasm and nuclei. (PMID:12489193)
• the localization of the arachidonic acid-binding site within the unique C-tail of S100A9 correlates with the fact that fatty acid binding has not yet been reported for other S100 proteins (PMID:12553726)
• S100A9 stimulates shedding of L-selectin, up-regulates and activates Mac-1/CD11b, induces neutrophil adhesion to fibrinogen in vitro, and is involved in neutrophil migration to in vivo inflammatory sites. (PMID:12626582)
• plays a prominent role in leukocyte trafficking and arachidonic acid metabolism; elevated levels of S100A9 and S100A8 in body fluids of inflamed tissues strengthen the view that these molecules are important players in fighting inflammation [review] (PMID:12645005)
• increased levels in fetal disease, premature rupture of membranes, and preterm labor (PMID:12710851)
• MRP8/MRP14 dimer behaves as a positive mediator of phagocyte NADPH oxidase regulation (PMID:12719414)
• Abrogation of MRP-14 activity with a specific antibody reduced the IL-8-stimulating potential of bronchial secretions, suggesting it was a stimulus to IL-8 production in the lung and may amplify neutrophilic inflammation in bronchial disease (PMID:12748056)
• Calprotectin, an antimicrobial peptide with antibacterial activity inhibits the growth of Borrelia burgdorferi. (PMID:12874352)
• MRP8/MRP14 complex inhibited proliferation and differentiation of myoblasts and induced apoptosis via activation of caspase-3 in a time- and dose-dependent manner. Activated macrophages can destroy and regenerate myocytes via MRP8/MRP14. (PMID:12937135)
• Since MRP-8/MRP-14 exhibit direct effects on leukocyte adhesion to the vascular endothelium, their extensive expression in the epidermis indicates an active role for these S-100 proteins in the initial phase of this systemic autoimmune disease. (PMID:13130482)
• protein expression profiles in HL-60 cells with ATRA treatment revealed a protein remarkably expressed in the differentiated cells, which was identified as S100A9 (PMID:14654085)
• Results of this study suggest that reduction of MRP14 expression is a frequent event in Chinese human esophageal cancer. (PMID:15040889)
• decreased expression of MRP8 and MRP14 might play an important role in the pathogenesis of human esophageal squamous cell carcinoma, being particularly associated with poor differentiation of tumor cells. (PMID:15069705)
• S100A8/A9 might induce apoptosis in tumor cells through a dual mechanism: one is zinc exclusion from the target cells, and the other represents an as yet undefined mechanism, possibly in a ligand-receptor dependent fashion. (PMID:15075348)
• Fibronectin adhesive capacity and integrin expression of monocytes of type 1 and type 2 diabetic patients is related to the subjects’ serum levels of MRP14. (PMID:15277376)
• expression of MRP8/MRP14 closely correlated with the inflammatory activity in systemic vasculitis (PMID:15598812)
• S100A8/A9 promotes phagocyte NADPH oxidase activation by supplying the enzyme with its cofactor arachidonic acid (PMID:15642721)
• Correlated with degree of differentiation. Absent in undifferentiated basalioma and strongly expressed in carcinoma in situ, keratoacanthoma, and differentiated squamous cell carcinoma. Expressed in superficial, differentiated region of normal epithelium. (PMID:15740587)
• MRP-14 is a potential mediator of p38 MAP kinase-dependent functional responses in human neutrophils. (PMID:15905572)
• data suggest that enhanced expression of S100A8, S100A9, and RAGE is an early event in prostate tumorigenesis and may contribute to development and progression or extension of prostate carcinomas (PMID:16033829)
• S100A8 and S100A9 in atherosclerotic plaque and calcifying matrix vesicles may significantly influence redox- and Ca2+-dependent processes during atherogenesis (PMID:16216873)
• This study indicates a potential role for pro-inflammatory S100A9 and S100A12 in pathogenesis caused by inflammation and protein complex formation in Alzheimer’s disease (PMID:16253391)
• heterodimeric S100 calcium binding protein A8/S100 calcium binding protein A9 might play a hitherto unknown role in triggering atherosclerosis in diabetes and renal failure (PMID:16573830)
• S100A8/A9 heterodimer, secreted extracellularly from activated tissue macrophages, may amplify proinflammatory cytokine responses in rheumatoid arthritis. (PMID:16613612)
• MRP-14 expression increases before ST-segment-elevation myocardial infarction (STEMI), and increasing plasma concentrations of MRP-8/14 among healthy individuals predict the risk of future cardiovascular events. (PMID:16682612)
• calcium-dependent formation of (S100A8/S100A9)2 tetramers is an essential prerequisite for biological function. (PMID:16690079)
• MRP-8/14 was mainly detected in human cervical mucus and showed a positive correlation with proinflammatory cytokines (PMID:16806487)
• MRP-8/MRP-14 are exclusively secreted by granulocytes in patients with acute Kawasaki disease, and intravenous immune globulin treatment suppresses their gene expression. (PMID:16979015)
• Zinc-binding, like calcium, induces (S100A8/S100A9)(2)-tetramers. (PMID:17050004)
• S100A8 and S100A9 are involved in the innate defense of the bronchial epithelium (PMID:17090475)
• Excessive release of cytotoxic MRP8/MRP14 by activated phagocytes might therefore present an important molecular pathomechanism contributing to endothelial damage during vasculitis and other inflammatory diseases (PMID:17095618)
• Authors hypothesize that L1AG might become internalized nonspecifically into target cells, perhaps by pinocytosis. This predicts cell survival of cultured stomach tumor cells as a function of L1AG concentration. (PMID:17126494)
• poly(ADP-ribose)polymerase-1 and Ku70/Ku80 are transcriptional regulators of S100A9 gene expression (PMID:17187679)
• In contrast, neutrophil adhesion to fibronectin was completely inhibited by anti-beta2 integrins, suggesting that S100A9-induced specific activation of beta2 integrin is essential to neutrophil adhesion. (PMID:17222807)
• data suggest unidentified natural ligands for CD69 and/or CD69 autoantibodies possibly affect joint-composing cell types through increased production of S100A9 in neutrophils, providing insight into functions of CD69 on neutrophils in rheumatoid arthritis (PMID:17237603)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	s100s	ENSDARG00000036773
danio_rerio	s100a10a	ENSDARG00000037425
danio_rerio	s100t	ENSDARG00000055589
mus_musculus	S100a9	ENSMUSG00000056071
mus_musculus	Gm5849	ENSMUSG00000096621
mus_musculus	Gm63964	ENSMUSG00000121904
mus_musculus	Gm63953	ENSMUSG00000121905
rattus_norvegicus	S100a9	ENSRNOG00000011483

Paralogs (21): CRNN (ENSG00000143536), S100A8 (ENSG00000143546), S100A7 (ENSG00000143556), S100B (ENSG00000160307), S100A1 (ENSG00000160678), S100A11 (ENSG00000163191), S100A12 (ENSG00000163221), S100P (ENSG00000163993), S100G (ENSG00000169906), S100Z (ENSG00000171643), S100A7A (ENSG00000184330), S100A3 (ENSG00000188015), S100A16 (ENSG00000188643), SNTN (ENSG00000188817), S100A13 (ENSG00000189171), S100A14 (ENSG00000189334), S100A4 (ENSG00000196154), S100A5 (ENSG00000196420), S100A2 (ENSG00000196754), S100A10 (ENSG00000197747), S100A6 (ENSG00000197956)

Protein

Protein identifiers

Protein S100-A9 — P06702 (reviewed: P06702)

Alternative names: Calgranulin-B, Calprotectin L1H subunit, Leukocyte L1 complex heavy chain, Migration inhibitory factor-related protein 14, S100 calcium-binding protein A9

All UniProt accessions (1): P06702

UniProt curated annotations — full annotation on UniProt →

Function. S100A9 is a calcium- and zinc-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response. It can induce neutrophil chemotaxis, adhesion, can increase the bactericidal activity of neutrophils by promoting phagocytosis via activation of SYK, PI3K/AKT, and ERK1/2 and can induce degranulation of neutrophils by a MAPK-dependent mechanism. Predominantly found as calprotectin (S100A8/A9) which has a wide plethora of intra- and extracellular functions. The intracellular functions include: facilitating leukocyte arachidonic acid trafficking and metabolism, modulation of the tubulin-dependent cytoskeleton during migration of phagocytes and activation of the neutrophilic NADPH-oxidase. Also participates in regulatory T-cell differentiation together with CD69. Activates NADPH-oxidase by facilitating the enzyme complex assembly at the cell membrane, transferring arachidonic acid, an essential cofactor, to the enzyme complex and S100A8 contributes to the enzyme assembly by directly binding to NCF2/P67PHOX. The extracellular functions involve pro-inflammatory, antimicrobial, oxidant-scavenging and apoptosis-inducing activities. Its pro-inflammatory activity includes recruitment of leukocytes, promotion of cytokine and chemokine production, and regulation of leukocyte adhesion and migration. Acts as an alarmin or a danger associated molecular pattern (DAMP) molecule and stimulates innate immune cells via binding to pattern recognition receptors such as Toll-like receptor 4 (TLR4) and receptor for advanced glycation endproducts (AGER). Binding to TLR4 and AGER activates the MAP-kinase and NF-kappa-B signaling pathways resulting in the amplification of the pro-inflammatory cascade. Has antimicrobial activity towards bacteria and fungi and exerts its antimicrobial activity probably via chelation of Zn(2+) which is essential for microbial growth. Can induce cell death via autophagy and apoptosis and this occurs through the cross-talk of mitochondria and lysosomes via reactive oxygen species (ROS) and the process involves BNIP3. Can regulate neutrophil number and apoptosis by an anti-apoptotic effect; regulates cell survival via ITGAM/ITGB and TLR4 and a signaling mechanism involving MEK-ERK. Its role as an oxidant scavenger has a protective role in preventing exaggerated tissue damage by scavenging oxidants. Can act as a potent amplifier of inflammation in autoimmunity as well as in cancer development and tumor spread. Has transnitrosylase activity; in oxidatively-modified low-densitity lipoprotein (LDL(ox))-induced S-nitrosylation of GAPDH on ‘Cys-247’ proposed to transfer the NO moiety from NOS2/iNOS to GAPDH via its own S-nitrosylated Cys-3. The iNOS-S100A8/A9 transnitrosylase complex is proposed to also direct selective inflammatory stimulus-dependent S-nitrosylation of multiple targets such as ANXA5, EZR, MSN and VIM by recognizing a [IL]-x-C-x-x-[DE] motif.

Subunit / interactions. Homodimer. Preferentially exists as a heterodimer or heterotetramer with S100A8 known as calprotectin (S100A8/A9). S100A9 interacts with ATP2A2. S100A9 interacts with AGER, and with the heterodimeric complex formed by TLR4 and LY96 in the presence of calcium and/or zinc ions. S100A9 binds quinoline-3-carboxamides in the presence of calcium and/or zinc ions. S100A9 interacts with amyloid-beta protein 40. Calprotectin (S100A8/9) interacts with CEACAM3 and tubulin filaments in a calcium-dependent manner. Heterotetrameric calprotectin (S100A8/A9) interacts with ANXA6 and associates with tubulin filaments in activated monocytes. Calprotectin (S100A8/9) interacts with NCF2/P67PHOX, RAC1, RAC2, CYBA and CYBB. Calprotectin (S100A8/9) interacts with NOS2 to form the iNOS-S100A8/A9 transnitrosylase complex; induced by LDL(ox). Calprotectin (S100A8/9) interacts with CD69.

Subcellular location. Secreted. Cytoplasm. Cytoskeleton. Cell membrane.

Tissue specificity. Calprotectin (S100A8/9) is predominantly expressed in myeloid cells. Except for inflammatory conditions, the expression is restricted to a specific stage of myeloid differentiation since both proteins are expressed in circulating neutrophils and monocytes but are absent in normal tissue macrophages and lymphocytes. Under chronic inflammatory conditions, such as psoriasis and malignant disorders, also expressed in the epidermis. Found in high concentrations at local sites of inflammation or in the serum of patients with inflammatory diseases such as rheumatoid, cystic fibrosis, inflammatory bowel disease, Crohn’s disease, giant cell arteritis, cystic fibrosis, Sjogren’s syndrome, systemic lupus erythematosus, and progressive systemic sclerosis. Involved in the formation and deposition of amyloids in the aging prostate known as corpora amylacea inclusions. Strongly up-regulated in many tumors, including gastric, esophageal, colon, pancreatic, bladder, ovarian, thyroid, breast and skin cancers.

Post-translational modifications. Phosphorylated. Phosphorylation inhibits activation of tubulin polymerization. S-nitrosylation of Cys-3 is implicated in LDL(ox)-induced S-nitrosylation of GAPDH at ‘Cys-247’ through a transnitrosylase mechanism involving a iNOS-S100A8/9 complex. Methylation at His-105 by METTL9 reduces zinc-binding without affecting heterodimerization with S100A8.

Similarity. Belongs to the S-100 family.

RefSeq proteins (1): NP_002956* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001751	S100/CaBP7/8-like_CS	Conserved_site
IPR002048	EF_hand_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR013787	S100_Ca-bd_sub	Domain
IPR018247	EF_Hand_1_Ca_BS	Binding_site

Pfam: PF01023

UniProt features (43 total): binding site 14, mutagenesis site 6, helix 5, modified residue 4, sequence conflict 3, turn 3, domain 2, strand 2, chain 1, sequence variant 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
4GGF	X-RAY DIFFRACTION	1.6
9ON4	X-RAY DIFFRACTION	1.66
8SJB	X-RAY DIFFRACTION	1.74
4XJK	X-RAY DIFFRACTION	1.76
1XK4	X-RAY DIFFRACTION	1.8
7QUV	X-RAY DIFFRACTION	1.85
8SJC	X-RAY DIFFRACTION	1.87
1IRJ	X-RAY DIFFRACTION	2.1
6DS2	X-RAY DIFFRACTION	2.1
5W1F	X-RAY DIFFRACTION	2.6
9OAA	ELECTRON MICROSCOPY	3.67
5I8N	SOLUTION NMR
7UI5	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P06702-F1	94.75	0.90

Functional residue map

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

Ligand- & substrate-binding residues (14): 31; 36; 67; 69; 71; 73; 78; 91; 95; 20; 23; 26 …

Post-translational modifications (4): 2, 3, 105, 113

Mutagenesis-validated functional residues (6):

Position	Phenotype
3	disrupts interaction with nos2 and inhibits ldl(ox)-induced gapdh s-nitrosylation; no effect on interaction with s100a8.
36	loss of resistance to bacterial invasion; when associated with q-78.
63	loss of antifungal activity.
78	loss of resistance to bacterial invasion; when associated with q-36.
81	no effect on antifungal activity.
83	loss of antifungal activity.

Function

Pathways and Gene Ontology

Reactome pathways

27 pathways

ID	Pathway
R-HSA-1236974	ER-Phagosome pathway
R-HSA-166058	MyD88:MAL(TIRAP) cascade initiated on plasma membrane
R-HSA-3000471	Scavenging by Class B Receptors
R-HSA-5602498	MyD88 deficiency (TLR2/4)
R-HSA-5603041	IRAK4 deficiency (TLR2/4)
R-HSA-5668599	RHO GTPases Activate NADPH Oxidases
R-HSA-5686938	Regulation of TLR by endogenous ligand
R-HSA-6798695	Neutrophil degranulation
R-HSA-6799990	Metal sequestration by antimicrobial proteins
R-HSA-1236975	Antigen processing-Cross presentation
R-HSA-1280218	Adaptive Immune System
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-166016	Toll Like Receptor 4 (TLR4) Cascade
R-HSA-168179	Toll Like Receptor TLR1:TLR2 Cascade
R-HSA-168188	Toll Like Receptor TLR6:TLR2 Cascade
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-168898	Toll-like Receptor Cascades
R-HSA-181438	Toll Like Receptor 2 (TLR2) Cascade
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-5260271	Diseases of Immune System
R-HSA-5602358	Diseases associated with the TLR signaling cascade
R-HSA-6803157	Antimicrobial peptides
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3
R-HSA-983169	Class I MHC mediated antigen processing & presentation

MSigDB gene sets: 951 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, GOBP_REGULATION_OF_RESPIRATORY_BURST, GOBP_REGULATION_OF_CELL_ACTIVATION, MODULE_92, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_IN_RESPONSE_TO_DNA_DAMAGE_BY_P53_CLASS_MEDIATOR, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_ICOSANOID_SECRETION, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, SHIPP_DLBCL_VS_FOLLICULAR_LYMPHOMA_UP, GOBP_B_CELL_HOMEOSTASIS, MCLACHLAN_DENTAL_CARIES_UP, GOBP_MYELOID_LEUKOCYTE_MIGRATION, HARRIS_HYPOXIA, GOBP_CELL_CHEMOTAXIS

GO Biological Process (26): leukocyte migration involved in inflammatory response (GO:0002523), chronic inflammatory response (GO:0002544), autophagy (GO:0006914), apoptotic process (GO:0006915), inflammatory response (GO:0006954), cell-cell signaling (GO:0007267), positive regulation of neuron projection development (GO:0010976), astrocyte development (GO:0014002), positive regulation of cell growth (GO:0030307), neutrophil chemotaxis (GO:0030593), regulation of toll-like receptor signaling pathway (GO:0034121), autocrine signaling (GO:0035425), peptidyl-cysteine S-trans-nitrosylation (GO:0035606), defense response to bacterium (GO:0042742), endothelial cell migration (GO:0043542), innate immune response (GO:0045087), positive regulation of inflammatory response (GO:0050729), defense response to fungus (GO:0050832), regulation of cytoskeleton organization (GO:0051493), regulation of respiratory burst involved in inflammatory response (GO:0060264), antimicrobial humoral immune response mediated by antimicrobial peptide (GO:0061844), neutrophil aggregation (GO:0070488), positive regulation of intrinsic apoptotic signaling pathway (GO:2001244), immune system process (GO:0002376), chemotaxis (GO:0006935), cellular oxidant detoxification (GO:0098869)

GO Molecular Function (10): calcium ion binding (GO:0005509), microtubule binding (GO:0008017), zinc ion binding (GO:0008270), antioxidant activity (GO:0016209), Toll-like receptor 4 binding (GO:0035662), calcium-dependent protein binding (GO:0048306), arachidonate binding (GO:0050544), RAGE receptor binding (GO:0050786), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (13): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), extracellular matrix (GO:0031012), secretory granule lumen (GO:0034774), extracellular exosome (GO:0070062), calprotectin complex (GO:1990660), S100A9 complex (GO:1990662), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Toll-like Receptor Cascades	3
Diseases associated with the TLR signaling cascade	2
Innate Immune System	2
Immune System	2
Toll Like Receptor 2 (TLR2) Cascade	2
Antigen processing-Cross presentation	1
Toll Like Receptor 4 (TLR4) Cascade	1
Toll Like Receptor TLR1:TLR2 Cascade	1
Toll Like Receptor TLR6:TLR2 Cascade	1
Binding and Uptake of Ligands by Scavenger Receptors	1
RHO GTPase Effectors	1
Antimicrobial peptides	1
Class I MHC mediated antigen processing & presentation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
inflammatory response	3
defense response	3
regulation of inflammatory response	2
leukocyte migration	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell communication	1
signaling	1
regulation of neuron projection development	1
neuron projection development	1
positive regulation of cell projection organization	1
glial cell development	1
astrocyte differentiation	1
regulation of cell growth	1
cell growth	1
positive regulation of growth	1
positive regulation of cellular process	1
granulocyte chemotaxis	1
neutrophil migration	1
toll-like receptor signaling pathway	1
regulation of pattern recognition receptor signaling pathway	1
cell-cell signaling	1
peptidyl-cysteine S-nitrosylation	1
response to bacterium	1
cell migration	1
immune response	1
defense response to symbiont	1
positive regulation of defense response	1
positive regulation of response to external stimulus	1
response to fungus	1
cytoskeleton organization	1
regulation of organelle organization	1
respiratory burst involved in inflammatory response	1
regulation of immune effector process	1
regulation of innate immune response	1

Protein interactions and networks

STRING

3369 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
S100A9	S100A8	P05109	989
S100A9	TLR4	O00206	926
S100A9	S100A7	P31151	698
S100A9	BSG	P35613	683
S100A9	LY96	Q9Y6Y9	660
S100A9	SDF4	Q9BRK5	620
S100A9	AGER	Q15109	618
S100A9	MPO	P05164	610
S100A9	CD68	P34810	601
S100A9	LYZL1	Q6UWQ5	596
S100A9	AZU1	P20160	587
S100A9	ANXA5	P08758	582
S100A9	ELANE	P08246	581
S100A9	TLR2	O60603	571
S100A9	LYZ	P00695	554

IntAct

225 interactions, top by confidence:

A	B	Type	Score
EGFR	GAPDH	psi-mi:“MI:0914”(association)	0.790
S100A9	S100A8	psi-mi:“MI:0914”(association)	0.750
S100A8	S100A9	psi-mi:“MI:0915”(physical association)	0.750
CFTR	XPO1	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
GAPDH	S100A8	psi-mi:“MI:0914”(association)	0.650
S100A8	GAPDH	psi-mi:“MI:0914”(association)	0.650
SINHCAF	TNRC18	psi-mi:“MI:0914”(association)	0.640
CCNC	MED19	psi-mi:“MI:0914”(association)	0.640
CD33	S100A9	psi-mi:“MI:0915”(physical association)	0.590
CD33	S100A9	psi-mi:“MI:2364”(proximity)	0.590
CD33	S100A9	psi-mi:“MI:0403”(colocalization)	0.590
S100A9	MAGEA1	psi-mi:“MI:0915”(physical association)	0.560
S100A9	MAGEA3	psi-mi:“MI:0915”(physical association)	0.560
S100A9	MAGEA6	psi-mi:“MI:0915”(physical association)	0.560
S100B	S100A9	psi-mi:“MI:0915”(physical association)	0.560
NPPA	A2ML1	psi-mi:“MI:0914”(association)	0.530
TBC1D22B	A2ML1	psi-mi:“MI:0914”(association)	0.530
AIRE	ALOX12B	psi-mi:“MI:0914”(association)	0.530
CBX1	ZNF292	psi-mi:“MI:0914”(association)	0.530
ING4	KAT7	psi-mi:“MI:0914”(association)	0.530
RYK	PCDH7	psi-mi:“MI:0914”(association)	0.530

BioGRID (313): NCF2 (Reconstituted Complex), S100A9 (Affinity Capture-MS), S100A9 (Affinity Capture-MS), S100A9 (Reconstituted Complex), S100A9 (Affinity Capture-MS), S100A9 (Affinity Capture-MS), S100A9 (Affinity Capture-MS), S100A9 (Affinity Capture-MS), S100A9 (Affinity Capture-MS), S100A9 (Affinity Capture-MS), S100A9 (Affinity Capture-MS), S100A9 (Biochemical Activity), S100A9 (Reconstituted Complex), S100A9 (Reconstituted Complex), S100A9 (Reconstituted Complex)

ESM2 similar proteins: A5PJN0, A7K6Y8, A7K6Y9, F1SSF9, O73763, O76038, O77791, P05109, P06702, P27005, P28318, P28782, P31725, P33763, P43367, P45961, P50115, P50116, P50117, P63083, P63084, P79105, P80511, Q01449, Q06A97, Q0VFG3, Q14ST5, Q28050, Q3MHP3, Q4R6C5, Q5E9G1, Q5SY68, Q5XJX1, Q63ZJ3, Q6AXZ3, Q6DJ05, Q6R556, Q6S5I3, Q75KU4, Q803V3

Diamond homologs: A7K6Y9, O77691, O77791, P02632, P02633, P02634, P02638, P02639, P04271, P04631, P05942, P05964, P06702, P06703, P07091, P10462, P14069, P20930, P23297, P24480, P25815, P26447, P27003, P28318, P28783, P29034, P29377, P30801, P33763, P33764, P35466, P35467, P50114, P50116, P50117, P56565, P62818, P62819, P63083, P63084

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
CEBPA	“up-regulates quantity by expression”	S100A9	“transcriptional regulation”
CEBPB	“up-regulates quantity by expression”	S100A9	“transcriptional regulation”
S100A9	“up-regulates activity”	TLR4	binding
S100A9	“up-regulates activity”	AGER	binding
S100A9	up-regulates	Differentiation
calcium(2+)	“up-regulates activity”	S100A9	“chemical activation”
S100A9	“up-regulates quantity by stabilization”	Tubulin	binding
STAT3	“up-regulates quantity by expression”	S100A9	“transcriptional regulation”
S100A9	down-regulates	Differentiation
S100A9	down-regulates	Macrophage_differentiation
S100A9	“form complex”	“Calprotectin complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	9
Likely benign	5
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

428 predictions. Top by Δscore:

Variant	Effect	Δscore
1:153358432:AGG:A	donor_loss	1.0000
1:153358433:GG:G	donor_loss	1.0000
1:153360641:CA:C	acceptor_loss	1.0000
1:153360642:A:AC	acceptor_loss	1.0000
1:153360642:A:AG	acceptor_gain	1.0000
1:153360642:AGAAG:A	acceptor_gain	1.0000
1:153360643:G:GT	acceptor_gain	1.0000
1:153360643:GA:G	acceptor_gain	1.0000
1:153360643:GAA:G	acceptor_gain	1.0000
1:153360643:GAAGG:G	acceptor_gain	1.0000
22:23894767:CGCA:C	acceptor_loss	1.0000
22:23894768:GCA:G	acceptor_loss	1.0000
22:23894769:CA:C	acceptor_loss	1.0000
22:23894769:CAG:C	acceptor_loss	1.0000
22:23894770:A:AG	acceptor_gain	1.0000
22:23894770:A:AT	acceptor_loss	1.0000
22:23894771:G:GC	acceptor_gain	1.0000
22:23894771:G:GG	acceptor_gain	1.0000
22:23894771:GT:G	acceptor_gain	1.0000
22:23894771:GTA:G	acceptor_gain	1.0000
22:23894771:GTAC:G	acceptor_gain	1.0000
22:23894771:GTACA:G	acceptor_gain	1.0000
22:23894774:C:G	acceptor_gain	1.0000
22:23894940:GACAG:G	donor_gain	1.0000
22:23894941:ACAGG:A	donor_loss	1.0000
22:23894942:CAGGT:C	donor_loss	1.0000
22:23894943:AG:A	donor_gain	1.0000
22:23894943:AGG:A	donor_loss	1.0000
22:23894943:AGGT:A	donor_loss	1.0000
22:23894944:GG:G	donor_gain	1.0000

AlphaMissense

774 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:153358338:T:C	F19L	0.996
1:153358340:C:A	F19L	0.996
1:153358340:C:G	F19L	0.996
1:153360719:T:C	F76L	0.990
1:153360721:C:A	F76L	0.990
1:153360721:C:G	F76L	0.990
1:153358351:C:T	S23F	0.984
1:153358425:T:C	F48L	0.981
1:153358427:T:A	F48L	0.981
1:153358427:T:G	F48L	0.981
1:153360728:T:C	F79L	0.980
1:153360730:C:A	F79L	0.980
1:153360730:C:G	F79L	0.980
1:153360694:C:A	D67E	0.975
1:153360694:C:G	D67E	0.975
1:153358402:T:C	L40P	0.974
1:153358339:T:C	F19S	0.972
1:153358393:T:C	F37S	0.968
1:153360761:T:C	S90P	0.968
1:153358417:T:C	L45P	0.966
1:153358378:T:C	L32P	0.965
1:153360720:T:C	F76S	0.964
1:153360726:A:T	E78V	0.963
1:153360692:G:C	D67H	0.962
1:153360743:G:C	A84P	0.961
1:153360750:T:C	L86P	0.960
1:153358350:T:C	S23P	0.959
1:153360693:A:C	D67A	0.959
1:153360693:A:T	D67V	0.957
1:153360720:T:G	F76C	0.957

dbSNP variants (sampled 300 via entrez): RS1000484791 (1:153358502 T>A,C,G), RS1000538901 (1:153359408 C>T), RS1001510694 (1:153360998 G>A,T), RS1001562416 (1:153359044 C>T), RS1001611542 (1:153358738 T>C), RS1001833872 (1:153358193 G>T), RS1001899338 (1:153360294 G>A), RS1001951690 (1:153360005 T>C), RS1002574074 (1:153359367 A>G), RS1003547429 (1:153356018 C>A,T), RS1003605057 (1:153361331 T>C), RS1003949261 (1:153361281 C>G), RS1004439490 (1:153360745 G>A,C), RS1004892718 (1:153360382 C>T), RS1005245594 (1:153357782 G>A)

Disease associations

OMIM: gene MIM:123886 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST005187_1	Matrix metalloproteinase-8 levels	5.000000e-13
GCST008916_87	Asthma	2.000000e-13
GCST90002380_82	Basophil percentage of white cells	5.000000e-14

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007992	basophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4296265 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

35 measured of 58 human assays (58 total across all organisms); most potent 35 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-(6-chloro-4-oxo-1H-pyridazin-3-yl)-1-(3,5-dichlorophenyl)methanesulfonamide	IC50	100 nM	US-10125125: N-(heteroaryl)-sulfonamide derivatives useful as S100-inhibitors
1-(3,5-dichlorophenyl)-N-(6-ethylsulfonyl-4-oxo-1H-pyridazin-3-yl)methanesulfonamide	IC50	100 nM	US-10125125: N-(heteroaryl)-sulfonamide derivatives useful as S100-inhibitors
N-(5-chloro-3-hydroxy-2-pyridinyl)-1-(3,5-dichlorophenyl)methanesulfonamide	IC50	120 nM	US-10125125: N-(heteroaryl)-sulfonamide derivatives useful as S100-inhibitors
N-(5-cyclopentylsulfonyl-3-hydroxy-2-pyridinyl)-1-(3,5-dichlorophenyl)methanesulfonamide	IC50	120 nM	US-10125125: N-(heteroaryl)-sulfonamide derivatives useful as S100-inhibitors
N-(5-cyano-3-hydroxy-2-pyridinyl)-1-(3,5-dichlorophenyl)methanesulfonamide	IC50	120 nM	US-10125125: N-(heteroaryl)-sulfonamide derivatives useful as S100-inhibitors
1-(3,5-dichlorophenyl)-N-(3-hydroxy-5-methylsulfonyl-2-pyridinyl)methanesulfonamide	IC50	140 nM	US-10125125: N-(heteroaryl)-sulfonamide derivatives useful as S100-inhibitors
N-(2-chloro-5-hydroxypyrimidin-4-yl)-1-(3,5-dichlorophenyl)methanesulfonamide	IC50	180 nM	US-10125125: N-(heteroaryl)-sulfonamide derivatives useful as S100-inhibitors
N-(6-bromo-2-oxo-1H-pyrazin-3-yl)-1-(3,4-dichlorophenyl)methanesulfonamide	IC50	250 nM	US-10125125: N-(heteroaryl)-sulfonamide derivatives useful as S100-inhibitors
1-(3-chloro-5-fluorophenyl)-N-(6-chloro-4-oxo-1H-pyridazin-3-yl)methanesulfonamide	IC50	300 nM	US-10125125: N-(heteroaryl)-sulfonamide derivatives useful as S100-inhibitors
N-(5-chloro-6-cyano-3-hydroxy-2-pyridinyl)-1-(3,5-dichlorophenyl)methanesulfonamide	IC50	390 nM	US-10125125: N-(heteroaryl)-sulfonamide derivatives useful as S100-inhibitors
N-(6-chloro-4-oxo-1H-pyridazin-3-yl)-1-(3-chlorophenyl)methanesulfonamide	IC50	410 nM	US-10125125: N-(heteroaryl)-sulfonamide derivatives useful as S100-inhibitors
1-(3,5-dichlorophenyl)-N-(6-methylsulfonyl-2-oxo-1H-pyrazin-3-yl)methanesulfonamide	IC50	420 nM	US-10125125: N-(heteroaryl)-sulfonamide derivatives useful as S100-inhibitors
N-(5-chloro-3-hydroxy-6-methylsulfonyl-2-pyridinyl)-1-(3,5-dichlorophenyl)methanesulfonamide	IC50	530 nM	US-10125125: N-(heteroaryl)-sulfonamide derivatives useful as S100-inhibitors
3,5-dichloro-N-(6-chloro-4-oxo-1H-pyridazin-3-yl)benzenesulfonamide	IC50	700 nM	US-10125125: N-(heteroaryl)-sulfonamide derivatives useful as S100-inhibitors
N-(6-chloro-4-oxo-1H-pyridin-3-yl)-1-(3,4-dichlorophenyl)methanesulfonamide	IC50	800 nM	US-10125125: N-(heteroaryl)-sulfonamide derivatives useful as S100-inhibitors
1-(2-chloro-5-cyanophenyl)-N-(6-chloro-4-oxo-1H-pyridazin-3-yl)methanesulfonamide	IC50	980 nM	US-10125125: N-(heteroaryl)-sulfonamide derivatives useful as S100-inhibitors
5-bromo-N-(6-chloro-4-oxo-1H-pyridazin-3-yl)-6-methoxypyridine-3-sulfonamide	IC50	1000 nM	US-10125125: N-(heteroaryl)-sulfonamide derivatives useful as S100-inhibitors
N-(5-chloro-3-hydroxy-2-pyridinyl)-1-(5-cyanothiophen-3-yl)methanesulfonamide	IC50	1110 nM	US-10125125: N-(heteroaryl)-sulfonamide derivatives useful as S100-inhibitors
2,5-dichloro-N-(6-chloro-4-oxo-1H-pyridin-3-yl)thiophene-3-sulfonamide	IC50	1200 nM	US-10125125: N-(heteroaryl)-sulfonamide derivatives useful as S100-inhibitors
5-bromo-6-methoxy-N-[4-oxo-6-(trifluoromethyl)-1H-pyridin-3-yl]pyridine-3-sulfonamide	IC50	1800 nM	US-10125125: N-(heteroaryl)-sulfonamide derivatives useful as S100-inhibitors
3,5-dichloro-N-(6-methylsulfonyl-2-oxo-1H-pyrazin-3-yl)benzenesulfonamide	IC50	1800 nM	US-10125125: N-(heteroaryl)-sulfonamide derivatives useful as S100-inhibitors
2,5-dichloro-N-(6-chloro-4-oxo-1H-pyridazin-3-yl)thiophene-3-sulfonamide	IC50	2000 nM	US-10125125: N-(heteroaryl)-sulfonamide derivatives useful as S100-inhibitors
3,5-dichloro-N-(5-chloro-4-oxo-1H-pyridin-3-yl)benzenesulfonamide	IC50	2100 nM	US-10125125: N-(heteroaryl)-sulfonamide derivatives useful as S100-inhibitors
3-chloro-N-(5-chloro-4-oxo-1H-pyridin-3-yl)-4-(trifluoromethoxy)benzenesulfonamide	IC50	2200 nM	US-10125125: N-(heteroaryl)-sulfonamide derivatives useful as S100-inhibitors
2,5-dichloro-N-(5-chloro-2-oxo-1H-pyridin-3-yl)thiophene-3-sulfonamide	IC50	2600 nM	US-10125125: N-(heteroaryl)-sulfonamide derivatives useful as S100-inhibitors
5-bromo-N-(5-chloro-4-oxo-1H-pyridin-3-yl)-6-methoxypyridine-3-sulfonamide	IC50	2800 nM	US-10125125: N-(heteroaryl)-sulfonamide derivatives useful as S100-inhibitors
5-bromo-N-(5-chloro-3-hydroxy-2-pyridinyl)pyridine-3-sulfonamide	IC50	3000 nM	US-10125125: N-(heteroaryl)-sulfonamide derivatives useful as S100-inhibitors
5-bromo-6-chloro-N-[3-hydroxy-5-(1-hydroxypropan-2-yl)-2-pyridinyl]pyridine-3-sulfonamide	IC50	3100 nM	US-10125125: N-(heteroaryl)-sulfonamide derivatives useful as S100-inhibitors
N-(5-chloro-2-oxo-1H-pyridin-3-yl)-1-(3,4-dichlorophenyl)methanesulfonamide	IC50	3100 nM	US-10125125: N-(heteroaryl)-sulfonamide derivatives useful as S100-inhibitors
N-(5-bromo-4-oxo-1H-pyridin-3-yl)-1-(3,5-dichlorophenyl)methanesulfonamide	IC50	3800 nM	US-10125125: N-(heteroaryl)-sulfonamide derivatives useful as S100-inhibitors
N-(5-cyano-4-oxo-1H-pyridin-3-yl)-1-(3,5-dichlorophenyl)methanesulfonamide	IC50	3900 nM	US-10125125: N-(heteroaryl)-sulfonamide derivatives useful as S100-inhibitors
N-(2-chloro-6-oxo-1H-pyrimidin-5-yl)-1-(3,5-dichlorophenyl)methanesulfonamide	IC50	4000 nM	US-10125125: N-(heteroaryl)-sulfonamide derivatives useful as S100-inhibitors
5-bromo-6-methoxy-N-(4-oxo-1H-pyridin-3-yl)pyridine-3-sulfonamide	IC50	4400 nM	US-10125125: N-(heteroaryl)-sulfonamide derivatives useful as S100-inhibitors
2,5-dichloro-N-(4-oxo-1H-pyridin-3-yl)thiophene-3-sulfonamide	IC50	4600 nM	US-10125125: N-(heteroaryl)-sulfonamide derivatives useful as S100-inhibitors
3-chloro-5-[(6-chloro-4-oxo-1H-pyridazin-3-yl)sulfamoylmethyl]-N,N-diethylbenzamide	IC50	5100 nM	US-10125125: N-(heteroaryl)-sulfonamide derivatives useful as S100-inhibitors

ChEMBL bioactivities

35 potent at pChembl≥5 of 35 total, top 35 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.00	IC50	100	nM	CHEMBL4452496
7.00	IC50	100	nM	CHEMBL4590954
6.92	IC50	120	nM	CHEMBL4522931
6.92	IC50	120	nM	CHEMBL4460770
6.92	IC50	120	nM	CHEMBL4440147
6.85	IC50	140	nM	CHEMBL4464961
6.75	IC50	180	nM	CHEMBL4458511
6.60	IC50	250	nM	CHEMBL4579094
6.52	IC50	300	nM	CHEMBL4458209
6.41	IC50	390	nM	CHEMBL4538232
6.39	IC50	410	nM	CHEMBL4461753
6.38	IC50	420	nM	CHEMBL4476679
6.28	IC50	530	nM	CHEMBL4442010
6.16	IC50	700	nM	CHEMBL4457224
6.10	IC50	800	nM	CHEMBL4457635
6.01	IC50	980	nM	CHEMBL4522111
6.00	IC50	1000	nM	CHEMBL4524415
5.96	IC50	1110	nM	CHEMBL4438952
5.92	IC50	1200	nM	CHEMBL4467121
5.75	IC50	1800	nM	CHEMBL4469212
5.75	IC50	1800	nM	CHEMBL4447502
5.70	IC50	2000	nM	CHEMBL4461591
5.68	IC50	2100	nM	CHEMBL4457470
5.66	IC50	2200	nM	CHEMBL4471866
5.58	IC50	2600	nM	CHEMBL4559489
5.55	IC50	2800	nM	CHEMBL4519288
5.52	IC50	3000	nM	CHEMBL4574262
5.51	IC50	3100	nM	CHEMBL4440704
5.51	IC50	3100	nM	CHEMBL4538953
5.42	IC50	3800	nM	CHEMBL4550309
5.41	IC50	3900	nM	CHEMBL4472089
5.40	IC50	4000	nM	CHEMBL4547602
5.36	IC50	4400	nM	CHEMBL4585830
5.34	IC50	4600	nM	CHEMBL4554925
5.29	IC50	5100	nM	CHEMBL4443656

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tretinoin	decreases reaction, increases expression, decreases expression	9
Tobacco Smoke Pollution	increases expression, affects expression, decreases expression	8
sodium arsenite	decreases expression, increases expression	7
Particulate Matter	increases abundance, increases expression, increases response to substance, affects cotreatment, decreases expression	6
Tetrachlorodibenzodioxin	decreases expression, increases expression, affects cotreatment	4
Air Pollutants	decreases expression, increases abundance	3
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation, increases expression, increases methylation	3
Estradiol	affects cotreatment, decreases expression, increases expression	3
Cyclosporine	decreases expression, increases expression	3
Decitabine	affects expression, increases expression	2
Arsenic Trioxide	increases expression	2
Cadmium	increases expression, increases abundance	2
Calcitriol	increases expression	2
Methotrexate	decreases expression, increases expression	2
Nickel	increases expression	2
Smoke	decreases expression, increases abundance	2
Tetradecanoylphorbol Acetate	increases expression	2
Valproic Acid	increases expression, increases methylation	2
Aflatoxin B1	increases expression, increases methylation	2
Antirheumatic Agents	decreases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
OTX015	increases expression	1
bisphenol F	decreases expression	1
4-oxoretinoic acid	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
tetrachloroisophthalonitrile	decreases expression	1
bisphenol A	decreases expression	1
lead acetate	decreases expression	1
potassium persulfate	increases expression	1

ChEMBL screening assays

10 unique, capped per target: 10 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4418746	Binding	Binding affinity to biotinylated recombinant human S100A9 expressed in Escherichia coli BL21 (DE3)/pET1120 (PLR757 ) assessed as inhibition of S100A9 binding to TLR4/MD2 using small molecule S100A9 binder in presence of physiological concen	N-(heteroaryl)-sulfonamide derivatives useful as s100-inhibitors

Clinical trials (associated diseases)

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