IL6

Summary

IL6 (interleukin 6, HGNC:6018) is a protein-coding gene on chromosome 7p15.3, encoding Interleukin-6 (P05231). Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. In precision oncology, IL6 Overexpression is associated with resistance to Cisplatin in Esophageal Carcinoma (CIViC Level D); 1 further curated variant–drug associations are listed below.

This gene encodes a cytokine that functions in inflammation and the maturation of B cells. In addition, the encoded protein has been shown to be an endogenous pyrogen capable of inducing fever in people with autoimmune diseases or infections. The protein is primarily produced at sites of acute and chronic inflammation, where it is secreted into the serum and induces a transcriptional inflammatory response through interleukin 6 receptor, alpha. The functioning of this gene is implicated in a wide variety of inflammation-associated disease states, including suspectibility to diabetes mellitus and systemic juvenile rheumatoid arthritis. Elevated levels of the encoded protein have been found in virus infections, including COVID-19 (disease caused by SARS-CoV-2).

Source: NCBI Gene 3569 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Kaposi sarcoma, susceptibility to (Definitive, GenCC)
• GWAS associations: 27 (top 5% of genes corpus-wide)
• Clinical variants (ClinVar): 27 total
• GTEx eGene: eQTL in 6 tissues, sQTL in 1 (q < 0.05)
• Phenotypes (HPO): 50
• Drug target: yes — 8 curated mechanism-of-action drugs; 3 molecules with ChEMBL bioactivity
• Approved drugs (ChEMBL mechanism of action): 1 — Siltuximab
• Precision-oncology evidence (CIViC): 2 curated variant–drug associations
• Constraint (gnomAD): pLI 0.20 (intermediate), LOEUF 0.88 (unconstrained)
• MANE Select transcript: NM_000600
• Interaction hub: 9,251 STRING partners (top 1% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6018
Approved symbol	IL6
Name	interleukin 6
Location	7p15.3
Locus type	gene with protein product
Status	Approved
Aliases	IL-6, BSF2, HGF, HSF
Ensembl gene	ENSG00000136244
Ensembl biotype	protein_coding
OMIM	147620
Entrez	3569

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 10 protein_coding, 1 retained_intron

MANE Select: ENST00000258743

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 3, TSL 3: 1, TSL 4: 1, TSL 5: 2

ENST00000258743, ENST00000401630, ENST00000401651, ENST00000404625, ENST00000406575, ENST00000407492, ENST00000426291, ENST00000464710, ENST00000485300, ENST00000964192, ENST00001141033

RefSeq mRNA: 3 — MANE Select: NM_000600 NM_000600, NM_001318095, NM_001371096

CCDS: CCDS5375, CCDS83166, CCDS94066

Canonical transcript exons

ENST00000258743 — 5 exons

Exon	Start	End
ENSE00001128385	22731406	22731998
ENSE00003614837	22729514	22729660
ENSE00003681793	22728693	22728806
ENSE00003846286	22727200	22727281
ENSE00003892968	22727444	22727634

Expression profiles

Bgee: expression breadth ubiquitous, 200 present calls, max score 97.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 86.0043 / max 8861.8142, expressed in 1153 samples.

Highest expression (Bgee): cartilage tissue, vena cava, gall bladder, uterine tube, omental fat pad.

Genetic regulation across tissues (GTEx eQTL / sQTL)

IL6 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 6 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

7 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	eqtl	1.1e-06	-0.18	7:22779715:C:G
Esophagus Mucosa	eqtl	1.6e-02	-0.66	7:23567781:T:C
Artery Tibial	sqtl	3.0e-02	-0.53	7:21820000:C:G
Muscle Skeletal	eqtl	3.1e-02	-0.13	7:22724226:C:G
Cells EBV-transformed lymphocytes	eqtl	3.4e-02	+0.24	7:21734378:A:G
Brain Cerebellar Hemisphere	eqtl	4.3e-02	+1.51	7:21751753:C:T
Brain Cerebellum	eqtl	4.6e-02	-0.71	7:23021436:T:C

FANTOM5 promoters

10 alternative TSS:

Promoter ID	TPM avg	Samples expressed
77592	80.4070	1028
77594	3.9224	838
77595	0.6025	203
77593	0.4505	272
77601	0.3042	122
77600	0.1060	38
77597	0.0878	32
77598	0.0513	20
77596	0.0484	16
77599	0.0241	9

Top tissues by expression

showing 100 of 281 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cartilage tissue	UBERON:0002418	97.93	gold quality
vena cava	UBERON:0004087	97.56	gold quality
gall bladder	UBERON:0002110	95.33	gold quality
left uterine tube	UBERON:0001303	90.82	gold quality
omental fat pad	UBERON:0010414	90.73	gold quality
peritoneum	UBERON:0002358	90.67	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.10	gold quality
smooth muscle tissue	UBERON:0001135	88.29	gold quality
mucosa of urinary bladder	UBERON:0001259	88.17	gold quality
adipose tissue of abdominal region	UBERON:0007808	88.10	gold quality
upper lobe of left lung	UBERON:0008952	87.97	gold quality
upper lobe of lung	UBERON:0008948	86.39	gold quality
islet of Langerhans	UBERON:0000006	85.77	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.43	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	85.18	gold quality
vermiform appendix	UBERON:0001154	84.69	gold quality
lung	UBERON:0002048	82.98	gold quality
trachea	UBERON:0003126	81.48	gold quality
ascending aorta	UBERON:0001496	81.29	gold quality
thoracic aorta	UBERON:0001515	80.79	gold quality
right atrium auricular region	UBERON:0006631	80.78	gold quality
pericardium	UBERON:0002407	80.09	gold quality
cardiac atrium	UBERON:0002081	79.75	gold quality
lower lobe of lung	UBERON:0008949	78.93	gold quality
muscle layer of sigmoid colon	UBERON:0035805	78.51	gold quality
lymph node	UBERON:0000029	78.34	gold quality
caecum	UBERON:0001153	78.25	gold quality
seminal vesicle	UBERON:0000998	78.19	gold quality
mucosa of stomach	UBERON:0001199	77.88	gold quality
rectum	UBERON:0001052	76.94	gold quality
hindlimb stylopod muscle	UBERON:0004252	76.90	gold quality
lower esophagus muscularis layer	UBERON:0035833	76.63	gold quality
adenohypophysis	UBERON:0002196	76.59	gold quality
lower esophagus	UBERON:0013473	76.58	gold quality
left coronary artery	UBERON:0001626	76.57	gold quality
type B pancreatic cell	CL:0000169	76.54	gold quality
diaphragm	UBERON:0001103	76.42	gold quality
right lung	UBERON:0002167	76.41	gold quality
descending thoracic aorta	UBERON:0002345	76.36	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	76.28	gold quality
mucosa of paranasal sinus	UBERON:0005030	75.94	gold quality
coronary artery	UBERON:0001621	75.77	gold quality
subcutaneous adipose tissue	UBERON:0002190	75.19	gold quality
adipose tissue	UBERON:0001013	74.53	gold quality
aorta	UBERON:0000947	74.33	gold quality
urinary bladder	UBERON:0001255	74.05	gold quality
tibial nerve	UBERON:0001323	73.99	gold quality
pleura	UBERON:0000977	73.86	gold quality
connective tissue	UBERON:0002384	73.50	gold quality
parietal pleura	UBERON:0002400	73.25	gold quality
heart	UBERON:0000948	73.05	gold quality
stromal cell of endometrium	CL:0002255	72.40	gold quality
visceral pleura	UBERON:0002401	71.81	gold quality
sigmoid colon	UBERON:0001159	71.73	gold quality
left lobe of thyroid gland	UBERON:0001120	71.54	gold quality
pancreas	UBERON:0001264	71.40	gold quality
heart left ventricle	UBERON:0002084	71.24	gold quality
spleen	UBERON:0002106	71.19	gold quality
right lobe of thyroid gland	UBERON:0001119	71.18	gold quality
cardiac ventricle	UBERON:0002082	71.02	gold quality
thyroid gland	UBERON:0002046	70.95	gold quality
minor salivary gland	UBERON:0001830	70.83	gold quality
right coronary artery	UBERON:0001625	70.80	gold quality
esophagus	UBERON:0001043	70.37	gold quality
gastrocnemius	UBERON:0001388	70.11	gold quality
lower esophagus mucosa	UBERON:0035834	69.83	gold quality
tibial artery	UBERON:0007610	69.62	gold quality
body of stomach	UBERON:0001161	69.61	gold quality
pituitary gland	UBERON:0000007	69.52	gold quality
popliteal artery	UBERON:0002250	69.45	gold quality
superficial temporal artery	UBERON:0001614	69.06	gold quality
epithelial cell of pancreas	CL:0000083	68.77	gold quality
skin of abdomen	UBERON:0001416	68.36	gold quality
bone marrow cell	CL:0002092	67.85	gold quality
saliva-secreting gland	UBERON:0001044	67.77	gold quality
apex of heart	UBERON:0002098	67.71	gold quality
mouth mucosa	UBERON:0003729	67.66	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	67.60	gold quality
spinal cord	UBERON:0002240	67.59	gold quality
fundus of stomach	UBERON:0001160	67.26	gold quality
left adrenal gland	UBERON:0001234	66.96	gold quality
large intestine	UBERON:0000059	66.90	gold quality
prostate gland	UBERON:0002367	66.84	gold quality
colon	UBERON:0001155	66.69	gold quality
muscle of leg	UBERON:0001383	66.00	gold quality
layer of synovial tissue	UBERON:0007616	65.97	gold quality
tibialis anterior	UBERON:0001385	65.96	gold quality
skin of leg	UBERON:0001511	65.87	gold quality
granulocyte	CL:0000094	65.79	gold quality
adrenal gland	UBERON:0002369	65.64	gold quality
stomach	UBERON:0000945	65.31	gold quality
left adrenal gland cortex	UBERON:0035825	65.22	gold quality
intestine	UBERON:0000160	65.20	gold quality
transverse colon	UBERON:0001157	65.12	gold quality
saphenous vein	UBERON:0007318	64.78	silver quality
esophagus mucosa	UBERON:0002469	64.46	gold quality
upper leg skin	UBERON:0004262	64.27	gold quality
adrenal cortex	UBERON:0001235	64.11	gold quality
tonsil	UBERON:0002372	64.08	gold quality
right ovary	UBERON:0002118	63.89	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	106.68
E-GEOD-130148	yes	5.02
E-MTAB-6379	no	2.29
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 75 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Urinary bladder	tissue	256.4	not detected
Adipose tissue	tissue	96.2	not detected
Bone marrow	tissue	43.3	medium
Pituitary gland	tissue	39.0
Gallbladder	tissue	36.2	not detected
Lung	tissue	33.7	not detected
Esophagus	tissue	31.1	not detected
Appendix	tissue	29.5	low
Smooth muscle	tissue	18.1	not detected
Pancreas	tissue	17.7	not detected
Rectum	tissue	15.2	not detected
Choroid plexus	tissue	15.1
Liver	tissue	12.5	not detected
Adrenal gland	tissue	11.9	not detected
Placenta	tissue	11.4	not detected
Prostate	tissue	10.0	not detected
Parathyroid gland	tissue	8.8	not detected
Lymph node	tissue	7.6	medium
Vagina	tissue	7.2	not detected
Heart muscle	tissue	6.7	not detected
Spleen	tissue	6.3	not detected
Thymus	tissue	5.8
Endometrium 1	tissue	5.1	not detected
Colon	tissue	5.0	not detected
Cervix	tissue	4.1	not detected
Breast	tissue	3.8	not detected
Tonsil	tissue	3.7	medium
Tongue	tissue	3.4
Fallopian tube	tissue	3.2	not detected
Ovary	tissue	3.0	not detected
Kidney	tissue	2.2	not detected
Periaqueductal gray	tissue	2.2
Spinal cord	tissue	2.0
Septum	tissue	1.9
Seminal vesicle	tissue	1.8	not detected
Hypothalamus	tissue	1.8
Ventral forebrain	tissue	1.8
Substantia nigra	tissue	1.7
Duodenum	tissue	1.6	not detected
Corpus callosum	tissue	1.6
Amygdala	tissue	1.5
Basal ganglia	tissue	1.4	not detected
Thyroid gland	tissue	1.4	not detected
Olfactory bulb	tissue	1.4
Cerebral cortex	tissue	1.3	not detected
Pons	tissue	1.3
Midbrain	tissue	1.3
Superior colliculi	tissue	1.3
Retrosplenial and cingulate cortex	tissue	1.3
Temporal cortex	tissue	1.3
Insular cortex	tissue	1.3
Prefrontal cortex	tissue	1.2
Retina	tissue	1.2
Putamen	tissue	1.2
Thalamus	tissue	1.2
Hippocampal formation	tissue	1.2
Entorhinal cortex	tissue	1.2
Retrosplenial cortex	tissue	1.2
Medulla oblongata	tissue	1.1
Occipital cortex	tissue	1.1

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Blood vessel (42.0), Area parastriata, superior (5.2), Dorsal tegmental nucleus (3.8), Anterior thalamic nucleus, ventral (2.9), Dorsolateral tegmental area (2.7).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

8 targets:

Target	Regulation
CXCL8	Activation
GCH1	Repression
HAMP	Activation
IL10	Activation
IL1B	Activation
NOS2	Activation
TNF	Activation
VTCN1	Activation

Upstream regulators (CollecTRI, top): AHR, ANXA1, AP1, APEX1, AR, ARNT, ATF1, ATF2, ATF3, ATF4, ATF6, BACH1, BCL3, BCL6, CEBPA, CEBPB, CEBPD, CEBPG, CREB1, CTNNB1, CUX1, DDIT3, E2F3, EGR1, EGR2, EHF, EIF2AK3, ENO1, EP300, ESR1, EZH2, FLI1, FOS, FOSL1, FOSL2, FOXA1, FOXA2, FOXC1, FOXM1, FOXN1

miRNA regulators (miRDB)

Targeting IL6 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 58 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4500	99.99	72.72	2367
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-4517	99.76	69.19	1867

Functional genomics

gnomAD constraint: pLI 0.2, LOEUF 0.881, missense Z -0.242 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000258743 — one region, missense o/e 1.06.

Literature-anchored findings (GeneRIF, showing 40)

• IL-6 stimulates proliferation of rat pituitary tumor cells in culture, inhibits secretion of prolactin and growth hormone and induces tyrosine phosphorylation of STAT3 in the cells. (PMID:11448119)
• Individuals genetically predisposed to produce high levels of IL-6 during aging are disadvantaged for longevity. (PMID:11500818)
• Data demonstrate that exercise activates transcription of the IL-6 gene in working skeletal muscle, a response that is dramatically enhanced when glycogen levels are low. (PMID:11687509)
• Interleukin-6 stimulates thyrotropin receptor expression in human orbital preadipocyte fibroblasts from patients with Graves’ ophthalmopathy (PMID:11716039)
• Interleukin (IL)-6 protein concentrations are increased approximately 18-fold in clinically localized prostate cancers when compared to normal prostate tissue. (PMID:11733366)
• Autocrine production of interleukin 6 causes multidrug resistance in breast cancer cells. (PMID:11751408)
• Levels of IL-6 were significantly higher in patients with dyslipidemia as compared with the healthy controls (PMID:11758653)
• Interleukin-6, tumor necrosis factor alpha and interferon gamma serum levels in patients with anorexia nervosa. (PMID:11774563)
• Pancreatic periacinar myofibroblasts secrete a large amount of IL-6 in response to proinflammatory cytokines IL-17, IL-1 beta, and TNF-alpha. (PMID:11777983)
• detection in pericardial fluid in coronary pathologies (PMID:11781191)
• Function and molecular modeling of the interaction between human interleukin 6 and its HNK-1 oligosaccharide ligands (PMID:11788581)
• Expression of Interleukin-6 (IL-6) and IL-6 receptor mRNA in human bone samples from pre- and postmenopausal women. (PMID:11792588)
• biosynthesis induced by tnf-alpha or interleukin 1 beta in human fibroblast-like synoviocytes increases with cell passage (PMID:11794009)
• Heat shock factor 1 represses transcription of the IL-1beta gene through physical interaction with the nuclear factor of interleukin 6 (PMID:11801594)
• Il-6 and oncostatin M act synergistically to promote growth in a new human myeloma cell line. (PMID:11818668)
• Certoparin but not UFH led to a dose-dependent increase in IL-6 from non-stimulated PBMC. (PMID:11820460)
• NADH significantly stimulated the dose-dependent release of IL-6 from peripheral blood leukocytes.The biological relevance of these data is discussed in the context of the recent use of NADH for the treatment of several neurodegenerative disorders. (PMID:11847482)
• Increased plasma levels of interleukin-6 and interleukin-8 are observed in beta-thalassaemia major patients and may be relevant in the pathophysiology of beta-thalassaemia (PMID:11855786)
• In dengue shock syndrome pts, IL-6 was significantly associated with both activation markers of coagulation (F1+2; p < 0.03) and fibrinolysis (PAPc; p = 0.002). IL6 is involved in the onset and regulation of hemostasis (PMID:11858187)
• IL-6 a key cytokine in in vitro and in vivo response of Sertoli cells to external gamma irradiation (PMID:11884027)
• Cancer cachexia is mediated in part by the induction of IL-6-like cytokines from the spleen. (PMID:11884029)
• secretion induced by combined effects of protein kinase C and ERK activation with TFF-papetide and TNF-alpha (PMID:11884401)
• Shedding of the interleukin-6 (IL-6) receptor (gp80) determines the ability of IL-6 to induce gp130 phosphorylation in human osteoblasts. (PMID:11884403)
• The -597 G–>A and -174 G–>C polymorphisms in the promoter of the IL-6 gene are associated with hyperandrogenism. (PMID:11889177)
• polymorphism -174G/C does not contribute substantially to hyperlipidaemia and Type II diabetes mellitus in Japanese men (PMID:11914754)
• results suggest that IL-6 is a mediator of the effects of Crohn’s serum on in vitro mineralization and may be a contributing factor to the osteopenia associated with Crohn’s disease (PMID:11918227)
• TNF-alpha induced IL-6 gene expression in airway smooth muscle (ASM) cells via a nuclear factor (NF)-kappaB-dependent pathway (PMID:11919083)
• Fas engagement increases expression of interleukin-6 in human glioma cells. (PMID:11949822)
• process of cervical dilatation during parturition at term is associated with an increased expression of interleukin-1 beta, interleukin-6 and interleukin-8 mRNA in the lower uterine segment (PMID:11950481)
• Reproductive hormone-induced, STAT3-mediated interleukin 6 action in normal and malignant human ovarian surface epithelial cells. (PMID:11959895)
• Secretion levels of sIL-2R, IL-6, IL-8, IL-10, and TNF-alpha, but not IL-4 and IL-12, are elevated in activated T-cells in large granular lymphocytic leukemia associated with autoimmune disorders. (PMID:11960393)
• the effects of high glucose in concert with AGII on IL-6 production in human mesangial cells and the modulation by blocking AGII (PMID:11961304)
• determine the cellular contents and concentrations of interleukin 6 (IL-6), interleukin 8 (IL-8) and tumour necrosis factor alpha (TNF-alpha) in fluids of patients with spermatocele or epididymal cyst (PMID:11966578)
• expressed in multiple sclerosis brain lesions (PMID:11984595)
• findings suggest that the IL-6prom G allele which may affect plasma IL-6 concentration might be a risk factor for sporadic AD in Japanese (PMID:11992567)
• high concentrations of IL-6 in the mid-secretory phase, the putative implantation window, and a further increase in the late secretory phase, the premenstrual period, support a role of IL-6 in the regulation of endometrial functions (PMID:12012622)
• IL-6 has a role in contributing directly to paclitaxel and doxorubicin resistance in U-2OS through a non-MDR-1 pathway. (PMID:12027404)
• secretion from acute myelogenous leukemia blasts was up-regulated by leptin (PMID:12031914)
• IL-6 induced activation of full-length LCAT promoter activity. A minimal IL-6 response element mapped within the distal promoter and was sufficient to mediate the IL-6 response (PMID:12032172)
• These results suggest that polymorphism of the IL-6 gene may be a useful marker for reduced bone mineral density. (PMID:12036196)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Il6	ENSMUSG00000025746
rattus_norvegicus	Il6	ENSRNOG00000010278

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:96559) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 157 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased anxiety-related response	3
abnormal astrocyte morphology	3
abnormal emotion/affect behavior	3
decreased susceptibility to injury	3
abnormal trabecular bone morphology	2
abnormal microglial cell morphology	2
decreased body weight	2
abnormal social investigation	2
abnormal object recognition memory	2
abnormal spatial learning	2
abnormal sleep pattern	2
abnormal osteoclast physiology	2
hepatic necrosis	2
abnormal inflammatory response	2
decreased inflammatory response	2
abnormal learning/memory/conditioning	2
seizures	2
gliosis	2
increased susceptibility to bacterial infection	2
abnormal neutrophil physiology	2
behavioral despair	2
abnormal neuron morphology	2
impaired febrile response	2
abnormal behavior	2
abnormal axon morphology	2

+132 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bubalus kerabau	Q2MH06	100.0%	Diamond
Bubalus bubalis	Q6V919	100.0%	Diamond
Ovis aries	P29455	99.5%	Diamond
Macaca fascicularis	P79341	99.5%	Diamond
Capra hircus	Q28319	99.5%	Diamond
Macaca thibetana	Q5I6E3	99.5%	Diamond
Bos taurus	P26892	99.0%	Diamond
Macaca mulatta	P51494	98.6%	Diamond
Camelus bactrianus	Q865W7	98.6%	Diamond
Lama glama	Q865X6	98.6%	Diamond
Cercocebus atys	P46650	98.1%	Diamond
Orcinus orca	Q28747	96.6%	Diamond
Delphinapterus leucas	Q9XT80	96.6%	Diamond
Mustela putorius furo	A3FBE9	96.0%	Diamond
Neogale vison	P41693	96.0%	Diamond
Canis lupus familiaris	P41323	95.7%	Diamond
Vulpes vulpes	Q25BC2	95.7%	Diamond
Saimiri sciureus	Q8MKH0	87.7%	Diamond
Phoca vitulina	Q28819	82.1%	Diamond
Sus scrofa	P26893	82.0%	Diamond
Felis catus	P41683	78.3%	Diamond
Equus caballus	Q95181	72.5%	Diamond
Marmota monax	O35736	51.0%	Diamond
Oryctolagus cuniculus	Q9MZR1	50.0%	Diamond
Gallus gallus	Q90YI0	47.9%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
STEAP1B	protein-coding	256227
IL6-AS1	ncRNA	541472
STEAP1B-AS1	ncRNA	100506178
TOMM7	protein-coding	54543

Protein

Protein identifiers

Interleukin-6 — P05231 (reviewed: P05231)

Alternative names: B-cell stimulatory factor 2, CTL differentiation factor, Hybridoma growth factor, Interferon beta-2

All UniProt accessions (8): A0A8Q3SJL1, B4DNV3, B5MC14, B5MC21, B5MCZ3, C9J5B0, P05231, Q75MH2

UniProt curated annotations — full annotation on UniProt →

Function. Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the intracellular IL6-signaling pathway. The interaction with the membrane-bound IL6R and IL6ST stimulates ‘classic signaling’, whereas the binding of IL6 and soluble IL6R to IL6ST stimulates ’trans-signaling’. Alternatively, ‘cluster signaling’ occurs when membrane-bound IL6:IL6R complexes on transmitter cells activate IL6ST receptors on neighboring receiver cells. IL6 is a potent inducer of the acute phase response. Rapid production of IL6 contributes to host defense during infection and tissue injury, but excessive IL6 synthesis is involved in disease pathology. In the innate immune response, is synthesized by myeloid cells, such as macrophages and dendritic cells, upon recognition of pathogens through toll-like receptors (TLRs) at the site of infection or tissue injury. In the adaptive immune response, is required for the differentiation of B cells into immunoglobulin-secreting cells. Plays a major role in the differentiation of CD4(+) T cell subsets. Essential factor for the development of T follicular helper (Tfh) cells that are required for the induction of germinal-center formation. Required to drive naive CD4(+) T cells to the Th17 lineage. Also required for proliferation of myeloma cells and the survival of plasmablast cells. Acts as an essential factor in bone homeostasis and on vessels directly or indirectly by induction of VEGF, resulting in increased angiogenesis activity and vascular permeability. Induces, through ’trans-signaling’ and synergistically with IL1B and TNF, the production of VEGF. Involved in metabolic controls, is discharged into the bloodstream after muscle contraction increasing lipolysis and improving insulin resistance. ‘Trans-signaling’ in central nervous system also regulates energy and glucose homeostasis. Mediates, through GLP-1, crosstalk between insulin-sensitive tissues, intestinal L cells and pancreatic islets to adapt to changes in insulin demand. Also acts as a myokine. Plays a protective role during liver injury, being required for maintenance of tissue regeneration. Also has a pivotal role in iron metabolism by regulating HAMP/hepcidin expression upon inflammation or bacterial infection. Through activation of IL6ST-YAP-NOTCH pathway, induces inflammation-induced epithelial regeneration.

Subunit / interactions. Component of a hexamer of two molecules each of IL6, IL6R and IL6ST; first binds to IL6R to associate with the signaling subunit IL6ST. Interacts with IL6R (via the N-terminal ectodomain); this interaction may be affected by IL6R-binding with SORL1, hence decreasing IL6 cis signaling. Interacts with SORL1 (via the N-terminal ectodomain); this interaction leads to IL6 internalization and lysosomal degradation. May form a trimeric complex with the soluble SORL1 ectodomain and soluble IL6R receptor; this interaction might stabilize circulating IL6, hence promoting IL6 trans signaling.

Subcellular location. Secreted.

Tissue specificity. Produced by skeletal muscle.

Post-translational modifications. N- and O-glycosylated.

Disease relevance. Rheumatoid arthritis systemic juvenile (RASJ) [MIM:604302] An inflammatory articular disorder with systemic onset beginning before the age of 16. It represents a subgroup of juvenile arthritis associated with severe extraarticular features and occasionally fatal complications. During active phases of the disorder, patients display a typical daily spiking fever, an evanescent macular rash, lymphadenopathy, hepatosplenomegaly, serositis, myalgia and arthritis. Disease susceptibility is associated with variants affecting the gene represented in this entry. A IL6 promoter polymorphism is associated with a lifetime risk of development of Kaposi sarcoma in HIV-infected men.

Induction. Plasma levels are highly increased upon exercise, due to enhanced production by contracting skeletal muscles. Up-regulated by coagulation factor Xa (F10) in PAR-1 (F2R)-dependent manner in cardiac fibroblasts.

Polymorphism. Genetic variations in IL6 may be correlated with bone mineral density (BMD). Low BMD is a risk factor for osteoporotic fracture. Osteoporosis is characterized by reduced bone mineral density, disruption of bone microarchitecture, and the alteration of the amount and variety of non-collagenous proteins in bone. Osteoporotic bones are more at risk of fracture.

Similarity. Belongs to the IL-6 superfamily.

RefSeq proteins (3): NP_000591, NP_001305024, NP_001358025 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003574	IL-6-like	Family
IPR009079	4_helix_cytokine-like_core	Homologous_superfamily
IPR030473	IL6/GCSF/MGF_CS	Conserved_site
IPR030474	IL-6/GCSF/MGF	Family

Pfam: PF00489

UniProt features (29 total): helix 10, mutagenesis site 5, strand 4, sequence variant 3, disulfide bond 2, signal peptide 1, chain 1, turn 1, modified residue 1, glycosylation site 1

Structure

Experimental structures (PDB)

17 structures by resolution:

PDB	Title	Method	Resolution (Å)
1ALU	HUMAN INTERLEUKIN-6	X-RAY DIFFRACTION	1.9
7NXZ	Synthetic glycoform of Human Interleukin 6	X-RAY DIFFRACTION	2
4CNI	Crystal structure of the Fab portion of Olokizumab in complex with IL- 6	X-RAY DIFFRACTION	2.2
4J4L	Modular evolution and design of the protein binding interface	X-RAY DIFFRACTION	2.3
4NI7	Crystal structure of human interleukin 6 in complex with a modified nucleotide aptamer …	X-RAY DIFFRACTION	2.4
4O9H	Structure of Interleukin-6 in complex with a Camelid Fab fragment	X-RAY DIFFRACTION	2.42
8YWQ	Crystal structure of the Fab fragment of the anti-IL-6 antibody I9H in complex with a …	X-RAY DIFFRACTION	2.51
4NI9	Crystal structure of human interleukin 6 in complex with a modified nucleotide aptamer …	X-RAY DIFFRACTION	2.55
5FUC	Biophysical and cellular characterisation of a junctional epitope antibody that locks …	X-RAY DIFFRACTION	2.7
4ZS7	Structural mimicry of receptor interaction by antagonistic IL-6 antibodies	X-RAY DIFFRACTION	2.93
8YWR	Crystal structure of the Fab fragment of the anti-IL-6 antibody 68F2 in complex with a …	X-RAY DIFFRACTION	2.93
8QY5	Structure of interleukin 6.	ELECTRON MICROSCOPY	3.1
8QY6	Structure of interleukin 6 (gp130 P496L mutant).	ELECTRON MICROSCOPY	3.16
8D82	Cryo-EM structure of human IL-6 signaling complex in detergent: model containing full …	ELECTRON MICROSCOPY	3.22
1P9M	Crystal structure of the hexameric human IL-6/IL-6 alpha receptor/gp130 complex	X-RAY DIFFRACTION	3.65
1IL6	HUMAN INTERLEUKIN-6, NMR, MINIMIZED AVERAGE STRUCTURE	SOLUTION NMR
2IL6	HUMAN INTERLEUKIN-6, NMR, 32 STRUCTURES	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P05231-F1	86.05	0.67

Antibody-complex structures (SAbDab)

7 antibodies co-crystallized with this protein: 4CNI, 4O9H, 4ZS7, 5FUC, 8YWQ, 8YWR, OLOKIZUMAB

Human Protein Atlas

Protein class: Predicted membrane proteins, Predicted secreted proteins, Predicted intracellular proteins, Plasma proteins, Cancer-related genes, Candidate cancer biomarkers, Candidate cardiovascular disease genes, Disease related genes, FDA approved drug targets, Biotech drugs, Human disease related genes

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): vesicles

Antibody reliability (HPA): IH supported · IF approved

Functional residue map

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

Post-translational modifications (1)

Type	Positions
Phosphoserine	81

Disulfide bonds (2)

Type	Positions
Disulfide bond	72–78, 101–111

Glycosylation sites (1)

Type	Positions
N-linked (glcnac…) asparagine	73

Mutagenesis-validated functional residues (5)

Position	Phenotype
185	no loss of activity.
204	87% loss of activity.
210	loss of activity.
212	loss of activity.
173	almost no loss of activity.

Function

Pathways and Gene Ontology

Reactome pathways

13 curated (TAS) of 35; 8 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

35 pathways:

ID	Pathway	Evidence
R-HSA-9660821	ADORA2B mediated anti-inflammatory cytokines production ⚕	curated
R-HSA-9662834	CD163 mediating an anti-inflammatory response ⚕	curated
R-HSA-9958825	Activation of STAT3 by cadherin engagement	curated
R-HSA-9968734	Differentiation of Circulating Monocytes	curated
R-HSA-6783783	Interleukin-10 signaling	curated
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling	curated
R-HSA-1059683	Interleukin-6 signaling	curated
R-HSA-112411	MAPK1 (ERK2) activation	curated
R-HSA-110056	MAPK3 (ERK1) activation	curated
R-HSA-8957275	Post-translational protein phosphorylation	curated
R-HSA-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	curated
R-HSA-2559582	Senescence-Associated Secretory Phenotype (SASP)	curated
R-HSA-8853884	Transcriptional Regulation by VENTX	curated
R-HSA-9662851	Anti-inflammatory response favouring Leishmania parasite infection ⚕	—
R-HSA-1643685	Disease ⚕	—
R-HSA-5663205	Infectious disease ⚕	—
R-HSA-9658195	Leishmania infection ⚕	—
R-HSA-9664433	Leishmania parasite growth and survival ⚕	—
R-HSA-9824443	Parasitic Infection Pathways ⚕	—
R-HSA-2559583	Cellular Senescence	—
R-HSA-8953897	Cellular responses to stimuli	—
R-HSA-2262752	Cellular responses to stress	—
R-HSA-1280215	Cytokine Signaling in Immune system	—
R-HSA-74160	Gene expression (Transcription)	—
R-HSA-212436	Generic Transcription Pathway	—
R-HSA-168256	Immune System	—
R-HSA-6783589	Interleukin-6 family signaling	—
R-HSA-5683057	MAPK family signaling cascades	—
R-HSA-5684996	MAPK1/MAPK3 signaling	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-597592	Post-translational protein modification	—
R-HSA-112409	RAF-independent MAPK1/3 activation	—
R-HSA-73857	RNA Polymerase II Transcription	—
R-HSA-162582	Signal Transduction	—
R-HSA-449147	Signaling by Interleukins	—

MSigDB gene sets: 1439 (showing top): PID_SHP2_PATHWAY, GSE45365_NK_CELL_VS_CD11B_DC_DN, GSE45365_NK_CELL_VS_BCELL_UP, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_REGULATION_OF_CELL_ACTIVATION, VERHAAK_AML_WITH_NPM1_MUTATED_DN, REACTOME_INTERLEUKIN_6_SIGNALING, CREL_01, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, MODULE_92, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, AP1_01, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOBP_REGULATION_OF_LIPID_STORAGE

GO Biological Process (99): neutrophil apoptotic process (GO:0001781), negative regulation of cytokine-mediated signaling pathway (GO:0001960), germinal center B cell differentiation (GO:0002314), hepatic immune response (GO:0002384), neutrophil mediated immunity (GO:0002446), monocyte chemotaxis (GO:0002548), positive regulation of immunoglobulin production (GO:0002639), positive regulation of acute inflammatory response (GO:0002675), positive regulation of leukocyte chemotaxis (GO:0002690), acute-phase response (GO:0006953), inflammatory response (GO:0006954), humoral immune response (GO:0006959), cell surface receptor signaling pathway via JAK-STAT (GO:0007259), positive regulation of cell population proliferation (GO:0008284), negative regulation of cell population proliferation (GO:0008285), vascular endothelial growth factor production (GO:0010573), regulation of vascular endothelial growth factor production (GO:0010574), positive regulation of vascular endothelial growth factor production (GO:0010575), positive regulation of gene expression (GO:0010628), positive regulation of epithelial to mesenchymal transition (GO:0010718), negative regulation of lipid storage (GO:0010888), response to activity (GO:0014823), cytokine-mediated signaling pathway (GO:0019221), platelet activation (GO:0030168), endocrine pancreas development (GO:0031018), neuron projection development (GO:0031175), response to peptidoglycan (GO:0032494), negative regulation of chemokine production (GO:0032682), positive regulation of chemokine production (GO:0032722), positive regulation of interleukin-1 beta production (GO:0032731), positive regulation of interleukin-10 production (GO:0032733), positive regulation of interleukin-17 production (GO:0032740), positive regulation of interleukin-21 production (GO:0032745), positive regulation of interleukin-6 production (GO:0032755), positive regulation of interleukin-8 production (GO:0032757), positive regulation of tumor necrosis factor production (GO:0032760), negative regulation of collagen biosynthetic process (GO:0032966), positive regulation of peptidyl-serine phosphorylation (GO:0033138), autocrine signaling (GO:0035425), maintenance of blood-brain barrier (GO:0035633), paracrine signaling (GO:0038001), positive regulation of T cell proliferation (GO:0042102), glucose homeostasis (GO:0042593), positive regulation of apoptotic process (GO:0043065), negative regulation of apoptotic process (GO:0043066), positive regulation of MAPK cascade (GO:0043410), negative regulation of fat cell differentiation (GO:0045599), positive regulation of osteoblast differentiation (GO:0045669), positive regulation of translation (GO:0045727), regulation of angiogenesis (GO:0045765), negative regulation of bone resorption (GO:0045779), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of receptor signaling pathway via JAK-STAT (GO:0046427), positive regulation of smooth muscle cell proliferation (GO:0048661), positive regulation of peptidyl-tyrosine phosphorylation (GO:0050731), negative regulation of neurogenesis (GO:0050768), regulation of insulin secretion (GO:0050796), defense response to Gram-negative bacterium (GO:0050829), defense response to Gram-positive bacterium (GO:0050830)

+39 more (showing top 60).

GO Molecular Function (5): cytokine activity (GO:0005125), interleukin-6 receptor binding (GO:0005138), growth factor activity (GO:0008083), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (4): extracellular region (GO:0005576), endoplasmic reticulum lumen (GO:0005788), plasma membrane (GO:0005886), interleukin-6 receptor complex (GO:0005896)

Reactome top-level categories

14 top-level categories:

Category	Pathways
RAF-independent MAPK1/3 activation	2
Signaling by Interleukins	2
Anti-inflammatory response favouring Leishmania parasite infection	2
Interleukin-6 family signaling	1
Cellular Senescence	1
Metabolism of proteins	1
Generic Transcription Pathway	1
Post-translational protein modification	1
Adherens junctions interactions	1
Developmental Cell Lineages	1
MAPK1/MAPK3 signaling	1
Immune System	1
RNA Polymerase II Transcription	1
Cellular responses to stimuli	1

GO top-level categories

53 GO namespaces:

Category	Terms
leukocyte chemotaxis	2
acute inflammatory response	2
cell population proliferation	2
regulation of cell population proliferation	2
vascular endothelial growth factor production	2
receptor ligand activity	2
neutrophil homeostasis	1
inflammatory cell apoptotic process	1
myeloid cell apoptotic process	1
leukocyte apoptotic process	1
regulation of cytokine-mediated signaling pathway	1
negative regulation of signal transduction	1
cytokine-mediated signaling pathway	1
negative regulation of response to cytokine stimulus	1
mature B cell differentiation involved in immune response	1
organ or tissue specific immune response	1
myeloid leukocyte mediated immunity	1
mononuclear cell migration	1
myeloid leukocyte migration	1
immunoglobulin production	1
regulation of immunoglobulin production	1
positive regulation of production of molecular mediator of immune response	1
regulation of acute inflammatory response	1
positive regulation of inflammatory response	1
positive regulation of leukocyte migration	1
regulation of leukocyte chemotaxis	1
positive regulation of chemotaxis	1
defense response	1
immune response	1
cell surface receptor signaling pathway via STAT	1
positive regulation of cellular process	1
negative regulation of cellular process	1
cytokine production	1
regulation of cytokine production	1
positive regulation of cytokine production	1
regulation of vascular endothelial growth factor production	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
epithelial to mesenchymal transition	1
regulation of epithelial to mesenchymal transition	1
positive regulation of cell differentiation	1
positive regulation of multicellular organismal process	1
cytokine receptor binding	1
growth factor receptor binding	1
protein binding	1
binding	1
cellular anatomical structure	1
endoplasmic reticulum	1
intracellular organelle lumen	1
membrane	1
cell periphery	1
plasma membrane signaling receptor complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 58 of 109 annotations. The rest are phylogenetic / computational / electronic (IEA).

58 experimentally-supported GO terms:

GO term	NS	Evidence
T-helper 17 cell lineage commitment	BP	direct assay
cell surface receptor signaling pathway via JAK-STAT	BP	direct assay
cell surface receptor signaling pathway via STAT	BP	direct assay
cellular response to hydrogen peroxide	BP	direct assay
cellular response to lipopolysaccharide	BP	mutant phenotype
cytokine-mediated signaling pathway	BP	direct assay
defense response to virus	BP	direct assay
glucose homeostasis	BP	direct assay
hepatic immune response	BP	direct assay
inflammatory response	BP	direct assay
inflammatory response to wounding	BP	direct assay
interleukin-6-mediated signaling pathway	BP	direct assay
negative regulation of apoptotic process	BP	direct assay
negative regulation of collagen biosynthetic process	BP	direct assay
negative regulation of primary miRNA processing	BP	genetic interaction
neuron projection development	BP	mutant phenotype
neutrophil apoptotic process	BP	direct assay
positive regulation of B cell activation	BP	direct assay
positive regulation of DNA-templated transcription	BP	direct assay
positive regulation of MAPK cascade	BP	direct assay
positive regulation of T cell proliferation	BP	direct assay
positive regulation of acute inflammatory response	BP	direct assay
positive regulation of apoptotic DNA fragmentation	BP	mutant phenotype
positive regulation of apoptotic process	BP	direct assay
positive regulation of cell population proliferation	BP	direct assay
positive regulation of chemokine production	BP	direct assay
positive regulation of cytokine production involved in inflammatory response	BP	genetic interaction
positive regulation of epithelial to mesenchymal transition	BP	direct assay
positive regulation of extracellular matrix disassembly	BP	mutant phenotype
positive regulation of gene expression	BP	direct assay
positive regulation of glial cell proliferation	BP	direct assay
positive regulation of immunoglobulin production	BP	direct assay
positive regulation of interleukin-1 beta production	BP	genetic interaction
positive regulation of interleukin-10 production	BP	direct assay
positive regulation of interleukin-6 production	BP	direct assay
positive regulation of interleukin-8 production	BP	direct assay
positive regulation of leukocyte adhesion to vascular endothelial cell	BP	direct assay
positive regulation of miRNA transcription	BP	direct assay
positive regulation of peptidyl-serine phosphorylation	BP	direct assay
positive regulation of peptidyl-tyrosine phosphorylation	BP	direct assay
positive regulation of platelet aggregation	BP	direct assay
positive regulation of receptor signaling pathway via JAK-STAT	BP	direct assay
positive regulation of receptor signaling pathway via STAT	BP	genetic interaction
positive regulation of smooth muscle cell proliferation	BP	direct assay
positive regulation of transcription by RNA polymerase II	BP	direct assay
positive regulation of translation	BP	direct assay
positive regulation of tumor necrosis factor production	BP	direct assay
positive regulation of vascular endothelial growth factor production	BP	mutant phenotype
regulation of glucagon secretion	BP	direct assay
regulation of insulin secretion	BP	direct assay
regulation of vascular endothelial growth factor production	BP	direct assay
response to glucocorticoid	BP	direct assay
vascular endothelial growth factor production	BP	direct assay
interleukin-6 receptor complex	CC	direct assay
cytokine activity	MF	direct assay
growth factor activity	MF	direct assay
identical protein binding	MF	physical interaction
interleukin-6 receptor binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 9,251 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IL6	IL1B	P01584	983
IL6	TNF	P01375	983
IL6	IL10	P22301	983
IL6	IFNG	P01579	979
IL6	CXCL8	P10145	972
IL6	IL17A	Q16552	972
IL6	IL4	P05112	966
IL6	CRP	P02741	965
IL6	IL1A	P01583	964
IL6	CD4	P01730	963
IL6	TLR4	O00206	962
IL6	TGFB1	P01137	958
IL6	CCL2	P13500	958
IL6	STAT3	P40763	956
IL6	IL2	P01585	953

IntAct

Human interaction partners of IL6 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

10 partners by confidence:

Partner	Interaction type	MIscore	Records
IL6R	physical association	0.910	14
IL6ST	association	0.840	3
SORL1	direct interaction	0.570	4
SORT1	direct interaction	0.570	4
ZBTB16	proximity	0.520	2
FAM20C	phosphorylation reaction	0.440	1
FCGR3B	physical association	0.400	1
MUSK	physical association	0.400	1
HRH1	proximity	0.270	1
SH3GL2	physical association	0.000	1

BioGRID (16 interactions; top human partners by supporting records): IL6R (Reconstituted Complex; 3 records), USP14 (Affinity Capture-Western; 2 records), CSK (Synthetic Lethality), ELAVL1 (Protein-RNA), HNRNPD (Protein-RNA), HRH1 (Co-localization), IL12RB1 (Negative Genetic), JAK1 (Positive Genetic), RC3H1 (Affinity Capture-RNA), SH3GL2 (Two-hybrid), ZBTB16 (Co-localization), ZC3H12A (Reconstituted Complex), ZC3H12B (Affinity Capture-RNA)

SIGNOR signaling

showing 34 of 37 signaling interactions:

A	Effect	B	Mechanism
IL6	up-regulates	IL6R	binding
NFATC1	“up-regulates quantity by expression”	IL6	“transcriptional regulation”
NFATC2	“up-regulates quantity by expression”	IL6	“transcriptional regulation”
NFATC3	“up-regulates quantity by expression”	IL6	“transcriptional regulation”
IL6	“down-regulates quantity by repression”	GCH1	“transcriptional regulation”
“A9/b1 integrin”	“up-regulates quantity by expression”	IL6
NfKb-p65/p50	up-regulates	IL6	“transcriptional regulation”
ATF2	up-regulates	IL6	“transcriptional regulation”
AP1	up-regulates	IL6	“transcriptional regulation”
IL6	“up-regulates activity”	IL6R	binding
Degranulation	“up-regulates quantity”	IL6
NfKb-p65/p50	“up-regulates quantity by expression”	IL6	“transcriptional regulation”
SRF	up-regulates	IL6
TP53	“up-regulates quantity by expression”	IL6	“transcriptional regulation”
TLR5	“up-regulates quantity by expression”	IL6	“transcriptional regulation”
IL6	up-regulates	Inflammation
S	“up-regulates quantity”	IL6
chloroquine	“down-regulates quantity”	IL6
IL1B	“up-regulates quantity by expression”	IL6	“transcriptional regulation”
TNF	“up-regulates quantity by expression”	IL6	“transcriptional regulation”
RELA	“up-regulates quantity by expression”	IL6	“transcriptional regulation”
“Activated PSC”	up-regulates	IL6
IFNG	“up-regulates activity”	IL6	“transcriptional regulation”
IL6	“up-regulates activity”	IL6ST	binding
IRF3	“up-regulates quantity by expression”	IL6	“transcriptional regulation”
PPP3CA	“up-regulates quantity by expression”	IL6	“transcriptional regulation”
PPP3CB	“up-regulates quantity by expression”	IL6	“transcriptional regulation”
PPP3CC	“up-regulates quantity by expression”	IL6	“transcriptional regulation”
Calcineurin	“up-regulates quantity by expression”	IL6
IL6	up-regulates	AMPK
ANXA1	“up-regulates quantity by expression”	IL6	“transcriptional regulation”
PP2B	“up-regulates quantity by expression”	IL6	“transcriptional regulation”
IL6	“up-regulates activity”	STAT3
IL6	“up-regulates activity”	IL6ST

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
★ IL-6 receptor-IL-6 complex	3	IL6ST, IL6, IL6R

Ligand–receptor pairs (CellPhoneDB) (1)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

1 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
IL6R;IL6ST	ligand	Signaling by Interleukin

Disease & clinical

Genetic variants

Variant evidence for IL6: 27 ClinVar records (0 pathogenic / likely pathogenic); 1 CIViC cancer variant; 5 PharmGKB clinical annotations; 27 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	15
Likely benign	4
Benign	5

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 27 predictions of 170):

Position(s)	Effect	Δscore	Sites
7:22728691–22728692	acceptor_loss	1.0000	3
7:22728807–22728808	donor_loss	1.0000	4
7:22729512–22729513	acceptor_loss	1.0000	5
7:22729622	donor_gain	1.0000
7:22729661–22729662	donor_loss	1.0000	5
7:22727282–22727283	donor_loss	0.9900	5
7:22728691	acceptor_loss	0.9900
7:22728807	donor_loss	0.9900
7:22729513	acceptor_loss	0.9900
7:22731395	acceptor_gain	0.9900

AlphaMissense

246 missense substitutions predicted likely pathogenic (of 1,395 scored), across 76 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D99	8	0.826	0.899
N88	8	0.721	0.898
C101	7	0.969	0.987
C111	7	0.964	0.981
F122	7	0.954	0.989
F201	7	0.949	0.993
C72	7	0.879	0.928
C78	7	0.877	0.941
F106	7	0.873	0.976
R207	7	0.855	0.953
F102	7	0.832	0.932
W185	7	0.819	0.966
P93	6	0.934	0.966
S205	5	0.927	0.990
Y128	5	0.756	0.820
F198	5	0.657	0.867
G118	4	0.901	0.914
G17	4	0.838	0.933
L92	4	0.809	0.916
F133	4	0.779	0.825

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	unfavorable	2.42e-06

Disease associations

OMIM: gene MIM:147620 | disease phenotypes:

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
Kaposi sarcoma, susceptibility to	Definitive	Autosomal dominant

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (1 panels, 1 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

1 panels:

Panel	Rating
COVID-19 research	green

Mondo (1): Kaposi sarcoma, susceptibility to (MONDO:0007845)

HPO phenotypes

50 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000099	Glomerulonephritis
HP:0000103	Polyuria
HP:0000819	Diabetes mellitus
HP:0000855	Insulin resistance
HP:0000938	Osteopenia
HP:0000969	Edema
HP:0000988	Skin rash
HP:0001034	Hypermelanotic macule
HP:0001369	Arthritis
HP:0001386	Joint swelling
HP:0001442	Typified by somatic mosaicism
HP:0001510	Growth delay
HP:0001701	Pericarditis
HP:0001744	Splenomegaly
HP:0001824	Weight loss
HP:0001945	Fever
HP:0001959	Polydipsia
HP:0001993	Ketoacidosis
HP:0002014	Diarrhea
HP:0002027	Abdominal pain
HP:0002037	Inflammation of the large intestine
HP:0002202	Pleural effusion
HP:0002240	Hepatomegaly
HP:0002408	Cerebral arteriovenous malformation
HP:0002591	Polyphagia
HP:0002664	Neoplasm
HP:0002716	Lymphadenopathy
HP:0002829	Arthralgia
HP:0002960	Autoimmunity
HP:0003074	Hyperglycemia
HP:0003281	Increased circulating ferritin concentration
HP:0003565	Elevated erythrocyte sedimentation rate
HP:0003584	Late onset
HP:0004890	Elevated pulmonary artery pressure
HP:0005214	Intestinal obstruction
HP:0005681	Juvenile idiopathic arthritis
HP:0005978	Type II diabetes mellitus
HP:0010982	Polygenic inheritance
HP:0011107	Recurrent aphthous stomatitis
HP:0011227	Elevated circulating C-reactive protein concentration
HP:0012122	Anterior uveitis
HP:0031819	Increased waist to hip ratio
HP:0032154	Aphthous ulcer
HP:0033430	Non-infectious meningitis
HP:0100279	Ulcerative colitis
HP:0100280	Crohn’s disease
HP:0100726	Kaposi’s sarcoma
HP:0100819	Intestinal fistula
HP:0410050	Decreased circulating 1,5 anhydroglucitol concentration

GWAS associations

27 associations:

Study	Trait	p-value
GCST006988_22	Blond vs. brown/black hair color	7e-50
GCST006629_88	Pulse pressure	2e-25
GCST007269_91	Pulse pressure	2e-19
GCST010043_104	Asthma	4e-14
GCST007614_15	C-reactive protein levels	8e-14
GCST000933_2	C-reactive protein	4e-11
GCST008474_7	Peripheral artery disease	4e-11
GCST009798_72	Asthma	3e-10
GCST007995_51	Asthma (childhood onset)	5e-10
GCST008916_60	Asthma	1e-9
GCST003425_1	Longevity	2e-9
GCST008362_199	Birth weight	2e-9
GCST008363_56	Offspring birth weight	2e-9
GCST002147_24	Fibrinogen	7e-9
GCST006575_49	Takayasu arteritis	7e-9
GCST008601_3	Longevity (age >99th survival percentile)	1e-8
GCST009870_3	Calcific aortic valve stenosis	1e-8
GCST005528_19	Juvenile idiopathic arthritis (oligoarticular or rheumatoid factor-negative polyarticular)	3e-8
GCST007800_85	Asthma (childhood onset)	3e-8
GCST008600_5	Longevity (age >90th survival percentile)	5e-8
GCST003137_1	Cerebrospinal fluid clusterin levels in APOEe4- carriers	7e-8
GCST006575_17	Takayasu arteritis	2e-7
GCST008363_55	Offspring birth weight	6e-7
GCST009597_173	Multiple sclerosis	8e-7
GCST007798_143	Asthma	3e-6
GCST001066_8	Dialysis-related mortality	4e-6
GCST007994_10	Asthma (age of onset)	8e-6

EFO canonical traits (from GWAS)

6 canonical traits:

EFO ID	Trait name
EFO:0004458	C-reactive protein measurement
EFO:0005763	pulse pressure measurement
EFO:0003924	hair color
EFO:0004344	birth weight
EFO:0005939	parental genotype effect measurement
EFO:0000266	aortic stenosis

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1795129 (SINGLE PROTEIN)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the IL6 protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

8 curated-mechanism drugs:

Drug	Modality	Max phase
SILTUXIMAB	Antibody	4
CLAZAKIZUMAB	Antibody	3
OLOKIZUMAB	Antibody	3
SIRUKUMAB	Antibody	3
ZILTIVEKIMAB	Antibody	3
ELSILIMOMAB	Antibody	2
PACIBEKITUG	Antibody	2
MRA 003 US	Unknown	1

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 142,281 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

3 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL131	PREDNISOLONE	4	142,034
CHEMBL3137316	FOSDAGROCORAT	2	219
CHEMBL3358954	BI 653048	1	28

Clinical evidence (CIViC)

Drug × variant × indication, from 2 curated evidence items. CIViC evidence level: A (validated) → B (clinical) → C (case study) → D (preclinical) → E (inferential).

2 predictive associations by evidence level:

Variant	Therapy	Indication	Effect	Level	CIViC
IL6 Overexpression	Cisplatin	Esophageal Carcinoma	Resistance	CIViC D	EID7851
IL6 Overexpression	Bazedoxifene	Rhabdomyosarcoma	Resistance	CIViC D	EID7956

CIViC curated variants (1)

Named clinical variants curated in CIViC for this gene (the catalogue beneath the predictive evidence above):

Overexpression.

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

5 annotations by evidence level (1 strongest → 4):

Variant	Association	Level	Drugs	Phenotypes
rs10499563	Efficacy	3	Tumor necrosis factor alpha (TNF-alpha) inhibitors	Inflammatory Bowel Diseases;Ulcerative Colitis
rs1800795	Efficacy	3	fenofibrate	Cardiovascular Disease
rs1800795	Efficacy	3	adalimumab;etanercept;infliximab	Rheumatoid arthritis
rs1800795	Toxicity	3	peginterferon alfa-2b;ribavirin	Chronic hepatitis C virus infection
rs1800795	Efficacy	3	Tumor necrosis factor alpha (TNF-alpha) inhibitors	Psoriasis

PharmGKB variants

2 variants:

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1800795	IL6	3	2.25	4	fenofibrate;Tumor necrosis factor alpha (TNF-alpha) inhibitors;adalimumab;etanercept;infliximab;peginterferon alfa-2b;ribavirin
rs10499563	IL6	3	3.50	1	Tumor necrosis factor alpha (TNF-alpha) inhibitors

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

20 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs1800795	adalimumab, etanercept, infliximab	Efficacy	Allele G is associated with increased response to adalimumab, etanercept or infliximab in people with Arthritis, Rheumatoid as compared to allele C.	PMID:24253594
rs10499563	Tumor necrosis factor alpha (TNF-alpha) inhibitors	Efficacy	Genotypes CC + CT is associated with increased response to Tumor necrosis factor alpha (TNF-alpha) inhibitors in people with Colitis, Ulcerative and Inflammatory Bowel Diseases as compared to genotype TT.	PMID:24776844
rs1800795	peginterferon alfa-2a, peginterferon alfa-2b, ribavirin	Efficacy	Genotype CC is associated with increased sustained virological response (svr) when treated with peginterferon alfa-2a, peginterferon alfa-2b and ribavirin in people with Hepatitis C, Chronic as compared to genotypes CG + GG.	PMID:27812403
rs1800797		Other	Genotypes AG + GG is associated with increased severity of Pain in children with Neoplasms as compared to genotype AA.	PMID:35335997
rs1800797	opioids	Dosage	Allele A is associated with decreased dose of opioids in children with Neoplasms and Pain as compared to allele G.	PMID:35335997
rs1800796	cisplatin, docetaxel, fluorouracil	Toxicity	Genotype CC is associated with increased likelihood of Thrombocytopenia when treated with cisplatin, docetaxel and fluorouracil in people with Carcinoma, Squamous Cell, Adenocarcinoma, Carcinoma, Adenosquamous or Esophageal Neoplasms as compared to genotypes CG + GG.	PMID:37898586
rs1800795	opioids	Dosage	Genotype CC is associated with increased dose of opioids in people with Pain and Neoplasms as compared to genotypes CG + GG.	PMID:38126330
rs1800795	opioids	Toxicity	Genotypes CG + GG is associated with decreased likelihood of somnolence, Nausea or adverse events when treated with opioids in people with Pain and Neoplasms as compared to genotype CC.	PMID:38126330
rs10499563	morphine	Toxicity	Genotype CC is associated with increased likelihood of Nausea, Fatigue or Depression when treated with morphine in people with Pain and Neoplasms as compared to genotypes CT + TT.	PMID:38824169
rs1800795	tacrolimus	Dosage	Genotype GG is associated with increased dose of tacrolimus in people with Kidney Transplantation as compared to genotypes CC + CG.	PMID:39069949
rs1800795	tacrolimus	Efficacy	Genotype GG is associated with decreased clinical benefit to tacrolimus in people with Kidney Transplantation as compared to genotypes CC + CG.	PMID:39535282
rs1800795	tacrolimus	Metabolism/PK	Genotype GG is associated with decreased dose-adjusted trough concentrations of tacrolimus in people with Kidney Transplantation as compared to genotypes CC + CG.	PMID:39535282
rs2069840	tocilizumab	Efficacy	Genotype CC is associated with decreased clinical benefit to tocilizumab in people with Rheumatoid arthritis as compared to genotype CG.	PMID:39718059
rs1800796	osimertinib	Efficacy	Genotypes CG + GG is associated with decreased likelihood of overall survival when treated with osimertinib in people with Non-Small Cell Lung Carcinoma as compared to genotype CC.	PMID:40156608
rs1800795	Tumor necrosis factor alpha (TNF-alpha) inhibitors	Efficacy	Allele G is associated with decreased response to Tumor necrosis factor alpha (TNF-alpha) inhibitors in people with Psoriasis as compared to allele C.	PMID:22158445
rs1800797	peginterferon alfa-2a	Efficacy	Allele G is associated with decreased response to peginterferon alfa-2a in people with Hepatitis C, Chronic as compared to allele A.	PMID:19387461
rs1800796	peginterferon alfa-2a	Efficacy	Allele G is associated with decreased response to peginterferon alfa-2a in people with Hepatitis C, Chronic as compared to allele C.	PMID:19387461
rs1800795	peginterferon alfa-2a	Efficacy	Allele G is associated with decreased response to peginterferon alfa-2a in people with Hepatitis C, Chronic as compared to allele C.	PMID:19387461
rs1800795	peginterferon alfa-2b, ribavirin	Toxicity	Genotype CC is associated with decreased risk of Depression when treated with peginterferon alfa-2b and ribavirin in people with Hepatitis C, Chronic as compared to genotypes CG + GG.	PMID:18458677
rs1800795	fenofibrate	Efficacy	Genotypes CC + CG are associated with increased response to fenofibrate in patients with a high risk of cardiovascular disease as compared to genotype GG.	PMID:16607077

Binding affinities (BindingDB)

127 measured of 132 human assays (133 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(4bS,7R,8aR)-4b-benzyl-N-(3,5-dimethylpyrazin-2-yl)-7-hydroxy-7-(trifluoromethyl)-5,6,8,8a,9,10-hexahydrophenanthrene-2-carboxamide	IC50	0.35 nM	US-8901310: Tricyclic compounds, compositions, and methods
(4bS,7R,8aS)-4b-benzyl-7-hydroxy-N-(2-methyl-3-pyridinyl)-10-oxo-7-(trifluoromethyl)-6,8,8a,9-tetrahydro-5H-phenanthrene-2-carboxamide	IC50	1.18 nM	US-8901310: Tricyclic compounds, compositions, and methods
(4bS,7S,8aR)-4b-benzyl-7-hydroxy-N-(2-methyl-3-pyridinyl)-7-(3,3,3-trifluoropropyl)-5,6,8,8a,9,10-hexahydrophenanthrene-2-carboxamide	IC50	1.22 nM	US-8901310: Tricyclic compounds, compositions, and methods
(4bS,7R,8aR,10R)-4b-benzyl-7,10-dihydroxy-N-(2-methyl-3-pyridinyl)-7-(trifluoromethyl)-5,6,8,8a,9,10-hexahydrophenanthrene-2-carboxamide	IC50	1.9 nM	US-8901310: Tricyclic compounds, compositions, and methods
(4bS,7R,8aR)-4b-benzyl-7-hydroxy-N-(4-methyl-3-pyridinyl)-7-(trifluoromethyl)-5,6,8,8a,9,10-hexahydrophenanthrene-2-carboxamide	IC50	2.06 nM	US-8901310: Tricyclic compounds, compositions, and methods
(4bS,7R,8aR)-4b-benzyl-7-hydroxy-N-(2-methyl-1-oxidopyridin-1-ium-3-yl)-7-(trifluoromethyl)-5,6,8,8a,9,10-hexahydrophenanthrene-2-carboxamide	IC50	2.13 nM	US-8901310: Tricyclic compounds, compositions, and methods
6-amino-2-butoxy-9-[[6-[4-[(cyclobutylamino)methyl]anilino]-3-pyridinyl]methyl]-7H-purin-8-one	EC50	2.5 nM	US-10508115: Toll-like receptor 7 (TLR7) agonists having heteroatom-linked aromatic moieties, conjugates thereof, and methods and uses therefor
6-amino-2-butoxy-9-[[6-[4-[(2-methylpropylamino)methyl]phenoxy]-3-pyridinyl]methyl]-7H-purin-8-one	EC50	3.77 nM	US-10508115: Toll-like receptor 7 (TLR7) agonists having heteroatom-linked aromatic moieties, conjugates thereof, and methods and uses therefor
6-amino-2-butoxy-9-[[6-[4-(pyrrolidin-1-ylmethyl)anilino]-3-pyridinyl]methyl]-7H-purin-8-one	EC50	3.8 nM	US-10508115: Toll-like receptor 7 (TLR7) agonists having heteroatom-linked aromatic moieties, conjugates thereof, and methods and uses therefor
(4bS,7S,8aR)-4b-benzyl-N-(2,4-dimethylpyrimidin-5-yl)-7-hydroxy-7-(3,3,3-trifluoropropyl)-5,6,8,8a,9,10-hexahydrophenanthrene-2-carboxamide	IC50	4.58 nM	US-8901310: Tricyclic compounds, compositions, and methods
6-amino-2-butoxy-9-[[10-methyl-7-[(propan-2-ylamino)methyl]phenothiazin-3-yl]methyl]-7H-purin-8-one	EC50	4.9 nM	US-10981914: Toll-like receptor 7 (TLR7) agonists having a tricyclic moiety, conjugates thereof, and methods and uses therefor
6-amino-2-butoxy-9-[[6-[4-[(cyclopropylmethylamino)methyl]phenoxy]-3-pyridinyl]methyl]-7H-purin-8-one	EC50	5.11 nM	US-10508115: Toll-like receptor 7 (TLR7) agonists having heteroatom-linked aromatic moieties, conjugates thereof, and methods and uses therefor
6-amino-2-butoxy-9-[[6-[4-[(2-methoxyethylamino)methyl]phenoxy]-3-pyridinyl]methyl]-7H-purin-8-one	EC50	5.81 nM	US-10508115: Toll-like receptor 7 (TLR7) agonists having heteroatom-linked aromatic moieties, conjugates thereof, and methods and uses therefor
6-amino-9-[[6-[4-[(2-bicyclo[1.1.1]pentanylamino)methyl]phenoxy]-3-pyridinyl]methyl]-2-butoxy-7H-purin-8-one	EC50	5.91 nM	US-10508115: Toll-like receptor 7 (TLR7) agonists having heteroatom-linked aromatic moieties, conjugates thereof, and methods and uses therefor
6-amino-2-butoxy-9-[[4-[4-[(2-methoxyethylamino)methyl]phenoxy]phenyl]methyl]-7H-purin-8-one	EC50	6.62 nM	US-10508115: Toll-like receptor 7 (TLR7) agonists having heteroatom-linked aromatic moieties, conjugates thereof, and methods and uses therefor
6-amino-2-butoxy-9-[[6-[4-[(propan-2-ylamino)methyl]phenoxy]-3-pyridinyl]methyl]-7H-purin-8-one	EC50	7.5 nM	US-10508115: Toll-like receptor 7 (TLR7) agonists having heteroatom-linked aromatic moieties, conjugates thereof, and methods and uses therefor
US10487084, Compound Ib-02	EC50	7.55 nM	US-10487084
6-amino-2-butoxy-9-[[3-fluoro-4-[4-[(oxan-4-ylamino)methyl]phenoxy]phenyl]methyl]-7H-purin-8-one	EC50	7.6 nM	US-10508115: Toll-like receptor 7 (TLR7) agonists having heteroatom-linked aromatic moieties, conjugates thereof, and methods and uses therefor
6-amino-2-butoxy-9-[[6-[4-[[(2-hydroxy-2-methylpropyl)amino]methyl]anilino]-3-pyridinyl]methyl]-7H-purin-8-one	EC50	7.8 nM	US-10508115: Toll-like receptor 7 (TLR7) agonists having heteroatom-linked aromatic moieties, conjugates thereof, and methods and uses therefor
(4bS,7R,8aR)-4b-benzyl-7-(difluoromethyl)-7-hydroxy-N-(2-methyl-3-pyridinyl)-5,6,8,8a,9,10-hexahydrophenanthrene-2-carboxamide	IC50	8.03 nM	US-8901310: Tricyclic compounds, compositions, and methods
6-amino-2-butoxy-9-[[6-[4-[(cyclopentylamino)methyl]phenoxy]-3-pyridinyl]methyl]-7H-purin-8-one	EC50	8.14 nM	US-10508115: Toll-like receptor 7 (TLR7) agonists having heteroatom-linked aromatic moieties, conjugates thereof, and methods and uses therefor
(4bS,7R,8aS)-4b-benzyl-7-hydroxy-N-(2-methyl-3-pyridinyl)-7-(trifluoromethyl)-5,6,8,8a-tetrahydrophenanthrene-2-carboxamide	IC50	9.12 nM	US-8901310: Tricyclic compounds, compositions, and methods
6-amino-2-butoxy-9-[[6-[4-[(oxetan-3-ylamino)methyl]phenoxy]-3-pyridinyl]methyl]-7H-purin-8-one	EC50	9.57 nM	US-10508115: Toll-like receptor 7 (TLR7) agonists having heteroatom-linked aromatic moieties, conjugates thereof, and methods and uses therefor
6-amino-2-butoxy-9-[[4-[[6-[(2-methylpropylamino)methyl]-2-pyridinyl]oxy]phenyl]methyl]-7H-purin-8-one	EC50	10.1 nM	US-10508115: Toll-like receptor 7 (TLR7) agonists having heteroatom-linked aromatic moieties, conjugates thereof, and methods and uses therefor
6-amino-2-butoxy-9-[[4-[4-[(cyclobutylamino)methyl]phenoxy]phenyl]methyl]-7H-purin-8-one	EC50	10.4 nM	US-10508115: Toll-like receptor 7 (TLR7) agonists having heteroatom-linked aromatic moieties, conjugates thereof, and methods and uses therefor
6-amino-2-butoxy-9-[[6-[4-[(2-hydroxyethylamino)methyl]phenoxy]-3-pyridinyl]methyl]-7H-purin-8-one	EC50	10.7 nM	US-10508115: Toll-like receptor 7 (TLR7) agonists having heteroatom-linked aromatic moieties, conjugates thereof, and methods and uses therefor
6-amino-9-[[6-[[4-(aminomethyl)piperidin-1-yl]methyl]-3-pyridinyl]methyl]-2-butoxy-7H-purin-8-one	EC50	11 nM	US-10919895: Toll-like receptor 7 (TLR7) agonists having a pyridine or pyrazine moiety, conjugates thereof, and methods and uses therefor
6-amino-2-butoxy-9-[[6-[[6-[(2-hydroxyethylamino)methyl]-3-pyridinyl]oxy]-3-pyridinyl]methyl]-7H-purin-8-one	EC50	12 nM	US-10508115: Toll-like receptor 7 (TLR7) agonists having heteroatom-linked aromatic moieties, conjugates thereof, and methods and uses therefor
(S)-7-[4-(3-cyano-2-hydroxypropyl)oxy-2-methoxyphenyl]-8-(5-fluoro-2-methyl-phenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one	IC50	13 nM	US-10189796: [4-(1,3,3-trimethyl-2-oxo-3,4-dihydro-1H-quinoxalin-7-yl)phenoxy]ethyloxy compound or salt thereof
6-amino-2-butoxy-9-[[6-[[6-[(2-methoxyethylamino)methyl]-3-pyridinyl]oxy]-3-pyridinyl]methyl]-7H-purin-8-one	EC50	13 nM	US-10508115: Toll-like receptor 7 (TLR7) agonists having heteroatom-linked aromatic moieties, conjugates thereof, and methods and uses therefor
6-amino-9-[[6-[(4-aminopiperidin-1-yl)methyl]-3-pyridinyl]methyl]-2-butoxy-7H-purin-8-one	EC50	13 nM	US-10919895: Toll-like receptor 7 (TLR7) agonists having a pyridine or pyrazine moiety, conjugates thereof, and methods and uses therefor
(R)-7-[4-(3-cyano-2-hydroxypropyl)oxy-2-methoxyphenyl]-8-(5-fluoro-2-methyl-phenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one	IC50	14 nM	US-10189796: [4-(1,3,3-trimethyl-2-oxo-3,4-dihydro-1H-quinoxalin-7-yl)phenoxy]ethyloxy compound or salt thereof
6-amino-2-butoxy-9-[[6-[[6-[(oxan-4-ylamino)methyl]-3-pyridinyl]oxy]-3-pyridinyl]methyl]-7H-purin-8-one	EC50	14 nM	US-10508115: Toll-like receptor 7 (TLR7) agonists having heteroatom-linked aromatic moieties, conjugates thereof, and methods and uses therefor
6-amino-2-butoxy-9-[[6-[4-[(oxan-4-ylamino)methyl]anilino]-3-pyridinyl]methyl]-7H-purin-8-one	EC50	14 nM	US-10508115: Toll-like receptor 7 (TLR7) agonists having heteroatom-linked aromatic moieties, conjugates thereof, and methods and uses therefor
6-amino-2-butoxy-9-[[6-[(cyclopropylamino)methyl]-3-pyridinyl]methyl]-7H-purin-8-one	EC50	14 nM	US-10919895: Toll-like receptor 7 (TLR7) agonists having a pyridine or pyrazine moiety, conjugates thereof, and methods and uses therefor
6-amino-2-butoxy-9-[[6-[4-[[(3,3-difluorocyclobutyl)amino]methyl]phenoxy]-3-pyridinyl]methyl]-7H-purin-8-one	EC50	14.3 nM	US-10508115: Toll-like receptor 7 (TLR7) agonists having heteroatom-linked aromatic moieties, conjugates thereof, and methods and uses therefor
6-amino-9-[[7-[(benzylamino)methyl]-10-methylphenothiazin-3-yl]methyl]-2-butoxy-7H-purin-8-one	EC50	14.4 nM	US-10457681: Toll-like receptor 7 (TLR7) agonists having a tricyclic moiety, conjugates thereof, and methods and uses therefor
6-amino-9-[[7-(anilinomethyl)-10-methylphenothiazin-3-yl]methyl]-2-butoxy-7H-purin-8-one	EC50	14.4 nM	US-10981914: Toll-like receptor 7 (TLR7) agonists having a tricyclic moiety, conjugates thereof, and methods and uses therefor
(S)-7-[4-(2,4-dihydroxybutyl)oxy-2-methoxyphenyl]-8-(5-fluoro-2-methyl-phenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one	IC50	15 nM	US-10189796: [4-(1,3,3-trimethyl-2-oxo-3,4-dihydro-1H-quinoxalin-7-yl)phenoxy]ethyloxy compound or salt thereof
6-amino-2-butoxy-9-[[6-[[6-(morpholin-4-ylmethyl)-3-pyridinyl]oxy]-3-pyridinyl]methyl]-7H-purin-8-one	EC50	15 nM	US-10508115: Toll-like receptor 7 (TLR7) agonists having heteroatom-linked aromatic moieties, conjugates thereof, and methods and uses therefor
6-amino-2-butoxy-9-[[4-[[6-[(cyclobutylamino)methyl]-2-pyridinyl]oxy]phenyl]methyl]-7H-purin-8-one	EC50	16.1 nM	US-10508115: Toll-like receptor 7 (TLR7) agonists having heteroatom-linked aromatic moieties, conjugates thereof, and methods and uses therefor
6-amino-2-butoxy-9-[[6-[4-[(2,2-difluoroethylamino)methyl]anilino]-3-pyridinyl]methyl]-7H-purin-8-one	EC50	17 nM	US-10508115: Toll-like receptor 7 (TLR7) agonists having heteroatom-linked aromatic moieties, conjugates thereof, and methods and uses therefor
6-amino-2-butoxy-9-[[4-[4-[(2-hydroxyethylamino)methyl]phenoxy]phenyl]methyl]-7H-purin-8-one	EC50	17.3 nM	US-10508115: Toll-like receptor 7 (TLR7) agonists having heteroatom-linked aromatic moieties, conjugates thereof, and methods and uses therefor
6-amino-2-butoxy-9-[[4-[4-[(cyclopropylamino)methyl]phenoxy]phenyl]methyl]-7H-purin-8-one	EC50	17.6 nM	US-10508115: Toll-like receptor 7 (TLR7) agonists having heteroatom-linked aromatic moieties, conjugates thereof, and methods and uses therefor
6-amino-2-butoxy-9-[[6-[4-[(2-methylsulfonylethylamino)methyl]phenoxy]-3-pyridinyl]methyl]-7H-purin-8-one	EC50	18.9 nM	US-10508115: Toll-like receptor 7 (TLR7) agonists having heteroatom-linked aromatic moieties, conjugates thereof, and methods and uses therefor
6-amino-2-butoxy-9-[[4-[4-[(cyclobutylamino)methyl]phenoxy]-3-fluorophenyl]methyl]-7H-purin-8-one	EC50	19 nM	US-10508115: Toll-like receptor 7 (TLR7) agonists having heteroatom-linked aromatic moieties, conjugates thereof, and methods and uses therefor
6-amino-9-[[4-[4-(azetidin-1-ylmethyl)phenoxy]-3-fluorophenyl]methyl]-2-butoxy-7H-purin-8-one	EC50	19 nM	US-10508115: Toll-like receptor 7 (TLR7) agonists having heteroatom-linked aromatic moieties, conjugates thereof, and methods and uses therefor
6-amino-9-[[6-[[(4-aminophenyl)methylamino]methyl]-3-pyridinyl]methyl]-2-butoxy-7H-purin-8-one	EC50	20 nM	US-10919895: Toll-like receptor 7 (TLR7) agonists having a pyridine or pyrazine moiety, conjugates thereof, and methods and uses therefor
6-amino-2-butoxy-9-[[4-[[6-[(oxan-4-ylamino)methyl]-2-pyridinyl]oxy]phenyl]methyl]-7H-purin-8-one	EC50	20.7 nM	US-10508115: Toll-like receptor 7 (TLR7) agonists having heteroatom-linked aromatic moieties, conjugates thereof, and methods and uses therefor
6-amino-2-butoxy-9-[[6-[[6-[(4-methylpiperazin-1-yl)methyl]-3-pyridinyl]oxy]-3-pyridinyl]methyl]-7H-purin-8-one	EC50	21 nM	US-10508115: Toll-like receptor 7 (TLR7) agonists having heteroatom-linked aromatic moieties, conjugates thereof, and methods and uses therefor

ChEMBL bioactivities

142 potent at pChembl≥5 of 145 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.96	IC50	1.1	nM	CHEMBL3647441
8.96	IC50	1.1	nM	CHEMBL3647443
8.89	IC50	1.3	nM	CHEMBL3647442
8.68	IC50	2.1	nM	CHEMBL3647445
8.60	EC50	2.5	nM	CHEMBL5967615
8.55	IC50	2.8	nM	CHEMBL3647447
8.42	EC50	3.77	nM	CHEMBL5993886
8.42	EC50	3.8	nM	CHEMBL5757665
8.40	IC50	4	nM	CHEMBL3647440
8.38	IC50	4.2	nM	PREDNISOLONE
8.37	IC50	4.3	nM	CHEMBL3647446
8.31	EC50	4.9	nM	CHEMBL5787912
8.29	EC50	5.11	nM	CHEMBL5977638
8.24	EC50	5.81	nM	CHEMBL5790478
8.23	EC50	5.91	nM	CHEMBL5992328
8.18	EC50	6.62	nM	CHEMBL6041191
8.16	EC50	6.9	nM	CHEMBL5907906
8.15	IC50	7	nM	CHEMBL3647444
8.12	EC50	7.55	nM	CHEMBL5746816
8.12	EC50	7.5	nM	CHEMBL5948820
8.12	EC50	7.6	nM	CHEMBL5778223
8.11	EC50	7.8	nM	CHEMBL5950488
8.09	EC50	8.14	nM	CHEMBL5865451
8.02	EC50	9.57	nM	CHEMBL5863568
8.00	EC50	10.1	nM	CHEMBL5757312
7.98	EC50	10.4	nM	CHEMBL6057462
7.97	EC50	10.7	nM	CHEMBL5935960
7.96	EC50	11	nM	CHEMBL6025451
7.92	EC50	12	nM	CHEMBL5801959
7.90	EC50	12.6	nM	CHEMBL5787912
7.89	IC50	13	nM	CHEMBL5854612
7.89	EC50	13	nM	CHEMBL6040007
7.89	EC50	13	nM	CHEMBL5878671
7.85	IC50	14	nM	CHEMBL6062967
7.85	EC50	14	nM	CHEMBL5769037
7.85	EC50	14	nM	CHEMBL5972079
7.85	EC50	14	nM	CHEMBL5766714
7.84	EC50	14.4	nM	CHEMBL5753489
7.84	EC50	14.3	nM	CHEMBL5926850
7.84	EC50	14.4	nM	CHEMBL5856275
7.82	IC50	15	nM	CHEMBL5842809
7.82	EC50	15	nM	CHEMBL5753489
7.82	EC50	15	nM	CHEMBL5849962
7.79	EC50	16.1	nM	CHEMBL5947975
7.77	EC50	17	nM	CHEMBL5845465
7.76	EC50	17.3	nM	CHEMBL5949769
7.75	EC50	17.6	nM	CHEMBL5936570
7.72	EC50	18.9	nM	CHEMBL5943152
7.72	EC50	19	nM	CHEMBL5985963
7.72	EC50	19	nM	CHEMBL5745822

PubChem BioAssay actives

8 with measured affinity, of 29 total; 8 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
(2R,3S,4S,4aR,10bS)-3,4,8,10-tetrahydroxy-2-(hydroxymethyl)-9-methoxy-3,4,4a,10b-tetrahydro-2H-pyrano[3,2-c]isochromen-6-one	1464042: Inhibition of IL6 (unknown origin)	ic50	0.2080	uM
ethyl (2Z)-7-methyl-2-[(4-morpholin-4-ylphenyl)methylidene]-3-oxo-5-thiophen-2-yl-8,8a-dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidine-6-carboxylate	1928289: Inhibition of IL-6 (unknown origin) by ELISA assay	ic50	0.5600	uM
ethyl (2Z)-7-methyl-2-[(4-morpholin-4-ylphenyl)methylidene]-3-oxo-5-(4-prop-2-enoxyphenyl)-8,8a-dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidine-6-carboxylate	1928289: Inhibition of IL-6 (unknown origin) by ELISA assay	ic50	0.6000	uM
ethyl (2Z)-7-methyl-2-[(4-morpholin-4-ylphenyl)methylidene]-3-oxo-5-phenyl-5H-[1,3]thiazolo[3,2-a]pyrimidine-6-carboxylate	1928289: Inhibition of IL-6 (unknown origin) by ELISA assay	ic50	0.8600	uM
(2E,5E)-2-[[4-[3-(dimethylamino)propoxy]phenyl]methylidene]-5-[[2-(trifluoromethyl)phenyl]methylidene]cyclopentan-1-one	1928289: Inhibition of IL-6 (unknown origin) by ELISA assay	ic50	1.2800	uM
18-benzyl-4,12,12-trimethyl-6-oxa-18-azapentacyclo[13.2.1.03,7.08,17.011,16]octadeca-1(17),3(7),4,8,10,15-hexaene-2,14-dione	1928289: Inhibition of IL-6 (unknown origin) by ELISA assay	ic50	1.6300	uM
(2E,5E)-2-[(4-hydroxy-3-methoxyphenyl)methylidene]-5-[[2-(trifluoromethyl)phenyl]methylidene]cyclopentan-1-one	1928289: Inhibition of IL-6 (unknown origin) by ELISA assay	ic50	1.9990	uM
N-[2-(4-ethylanilino)-1,3-benzoxazol-5-yl]benzamide	1452825: Inhibition of IL-6 signaling pathway in human HepG2 cells transfected with p-STAT3-Luc assessed as reduction in IL-6 induced STAT3 phosphorylation preincubated for 1 hr followed by IL-6 induction measured after 10 mins by immunoblot analysis	ic50	5.8000	uM

CTD chemical–gene interactions

1148 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Lipopolysaccharides	decreases reaction, affects expression, affects reaction, affects cotreatment, affects response to substance (+8 more)	187
Particulate Matter	increases phosphorylation, affects cotreatment, decreases reaction, increases reaction, affects response to substance (+7 more)	102
Resveratrol	decreases expression, decreases reaction, increases secretion, increases reaction, affects expression (+8 more)	42
Air Pollutants	affects cotreatment, increases abundance, increases expression, affects secretion, decreases expression (+5 more)	38
Vehicle Emissions	affects response to substance, affects expression, affects secretion, increases reaction, affects reaction (+7 more)	37
SB 203580	decreases reaction, increases expression, increases abundance, increases reaction, increases secretion (+5 more)	32
Tetradecanoylphorbol Acetate	increases stability, affects cotreatment, decreases reaction, increases expression, affects reaction (+2 more)	31
Dexamethasone	increases response to substance, increases reaction, decreases reaction, decreases response to substance, decreases expression (+6 more)	29
Acetylcysteine	decreases secretion, decreases expression, affects cotreatment, decreases reaction, increases expression (+3 more)	26
bisphenol A	decreases reaction, increases expression, increases secretion, decreases expression, decreases secretion (+5 more)	24
sodium arsenite	decreases reaction, increases expression, increases secretion, increases abundance, increases phosphorylation (+4 more)	22
3-(4-methylphenylsulfonyl)-2-propenenitrile	increases expression, increases secretion, increases abundance, decreases expression, decreases secretion (+2 more)	21
Quercetin	increases reaction, affects cotreatment, increases expression, decreases expression, increases secretion (+4 more)	21
lipopolysaccharide, Escherichia coli O111 B4	increases secretion, increases reaction, decreases reaction, affects cotreatment, increases expression (+4 more)	20
Tobacco Smoke Pollution	affects reaction, decreases expression, affects expression, decreases secretion, decreases reaction (+5 more)	20
Cadmium Chloride	increases abundance, increases secretion, decreases activity, decreases expression, increases reaction (+4 more)	20
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases response to substance, decreases reaction, increases expression, increases secretion, affects cotreatment (+1 more)	18
Cadmium	increases expression, affects cotreatment, affects expression, increases secretion, decreases reaction (+3 more)	18
Hydrogen Peroxide	decreases reaction, increases reaction, increases secretion, affects binding, decreases expression (+4 more)	18
Mustard Gas	affects reaction, affects expression, increases reaction, increases secretion, decreases reaction (+1 more)	18
Glucose	increases reaction, affects expression, affects reaction, decreases reaction, increases expression (+2 more)	17
Ozone	increases abundance, increases reaction, increases secretion, decreases expression, affects cotreatment (+2 more)	17
Calcimycin	affects cotreatment, decreases reaction, increases expression, increases reaction, increases secretion	15
Curcumin	increases secretion, increases abundance, affects cotreatment, decreases expression, increases reaction (+2 more)	15
Silicon Dioxide	decreases reaction, increases secretion, increases expression, increases reaction, affects reaction	15
pyrazolanthrone	decreases reaction, increases expression, increases secretion, affects cotreatment, increases reaction	14
Estradiol	affects reaction, decreases secretion, affects binding, decreases expression, affects cotreatment (+7 more)	14
1-Methyl-4-phenylpyridinium	decreases reaction, increases expression, increases secretion, affects reaction, decreases response to substance (+1 more)	14
lipopolysaccharide, E coli O55-B5	decreases reaction, increases expression, increases secretion, affects cotreatment, increases reaction (+2 more)	13
Paraquat	increases secretion, affects cotreatment, increases activity, decreases reaction, increases expression	13

ChEMBL screening assays

16 unique, capped per target: 16 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1809407	Binding	Inhibition of IL-6 at 4 uM	Discovery of N-(1-ethylpropyl)-[3-methoxy-5-(2-methoxy-4-trifluoromethoxyphenyl)-6-methyl-pyrazin-2-yl]amine 59 (NGD 98-2): an orally active corticotropin releasing factor-1 (CRF-1) receptor antagonist. — *J Med Chem*

Cellosaurus cell lines

8 cell lines: 6 cancer cell line, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A1SE	S6B45	Cancer cell line	Female
CVCL_B1FZ	Abcam A-549 IL6 KO	Cancer cell line	Male
CVCL_D7S7	Ubigene A-549 IL6 KO	Cancer cell line	Male
CVCL_E0F4	Ubigene HeLa IL6 KO	Cancer cell line	Female
CVCL_E6UB	Genomeditech HEK-293 H_IL6 Reporter	Transformed cell line	Female
CVCL_F4QD	HyCyte PC-9 stable cell line for hIL6 overexpression	Cancer cell line	Male
CVCL_LF76	N263	Transformed cell line	Male
CVCL_Y023	ABC-1#IL-6	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT00380770	Phase 4	COMPLETED	HIV/AIDS Kaposis Sarcoma: Comparison of Response to HAART vs HAART Plus CXT
NCT00444379	Phase 4	COMPLETED	Anti-Retrovirals for Kaposi’s Sarcoma
NCT00168987	Phase 4	COMPLETED	Influence of an Oral Nutritional Supplement Rich in Omega-3 Fatty Acids on Functional State and Quality of Life in Malnourished Patients With Gastroenterological Tumors
NCT00280709	Phase 4	COMPLETED	Biliary Metal Stent Study: Metal Stents for Management of Distal Malignant Biliary Obstruction
NCT00797121	Phase 4	UNKNOWN	Preoperative Biliary Drainage for Resectable Hilar Cholangiocarcinoma
NCT01111591	Phase 4	UNKNOWN	Cyclooxygenase-2 Inhibitor for Adjuvant Anticancer Effect in Patients With Biliary-pancreas Cancer
NCT01256034	Phase 4	COMPLETED	Effects of Preoperative Immunonutrition in Patients Undergoing Pancreaticoduodenectomy
NCT01256047	Phase 4	COMPLETED	Effects of Preoperative Immunonutrition in Patients Undergoing Hepatectomy
NCT01642875	Phase 4	UNKNOWN	Early Oral Versus Enteral Nutrition After Pancreatoduodenectomy
NCT02027311	Phase 4	COMPLETED	Etomidate vs. Midazolam for Sedation During ERCP
NCT02174575	Phase 4	WITHDRAWN	Anesthetic Agents and Acute Kidney Injury After Liver Resection Surgery
NCT07486713	Phase 4	RECRUITING	Olutasidenib DDI Study in Patients With IDH1 Mutation Positive Malignancies
NCT01352117	Phase 3	COMPLETED	Antiretroviral Therapy (ART) Alone or With Delayed Chemo Versus ART With Immediate Chemo for Limited AIDS-related Kaposi’s Sarcoma
NCT05411237	Phase 3	NOT_YET_RECRUITING	Paclitaxel and Pegylated Liposomal Doxorubicin for Treatment of HIV-related Kaposi Sarcoma
NCT00540735	Phase 3	TERMINATED	Efficiency Evaluation of Photodynamic Therapy With Photofrin® on Unresectable Type III or IV Cholangiocarcinomas
NCT00653978	Phase 3	UNKNOWN	Unilateral Versus Bilateral Stents for Bismuth Type II and III Malignant Hilar Strictures
NCT00809081	Phase 3	UNKNOWN	Early Enteral Feeding After Pylorus Preserving Pancreatoduodenectomy
NCT00869635	Phase 3	COMPLETED	S-1 and Photodynamic Therapy in Cholangiocarcinoma
NCT00907413	Phase 3	TERMINATED	Photodynamic Therapy (PDT) Trial for Palliation of Cholangiocarcinoma
NCT01926236	Phase 3	COMPLETED	Active Symptom Control Alone or With mFOLFOX Chemotherapy for Locally Advanced/ Metastatic Biliary Tract Cancers
NCT02170090	Phase 3	ACTIVE_NOT_RECRUITING	Adjuvant Chemotherapy With Gemcitabine and Cisplatin Compared to Standard of Care After Curative Intent Resection of Biliary Tract Cancer
NCT02548195	Phase 3	UNKNOWN	Oxaliplatin+Gemcitabine vs Capecitabine as Adjuvant Therapy for Intrahepatic Cholangiocarcinoma
NCT02773485	Phase 3	UNKNOWN	Chemo Alone or in Combination With Radiation in Unresectable Cholangiocarcinoma
NCT02853474	Phase 3	COMPLETED	Early Palliative Care in Patients With Metastatic Upper Gastrointestinal Cancers Treated With First-line Chemotherapy
NCT02989857	Phase 3	COMPLETED	Study of AG-120 in Previously Treated Advanced Cholangiocarcinoma With IDH1 Mutations (ClarIDHy)
NCT03656536	Phase 3	TERMINATED	A Study to Evaluate the Efficacy and Safety of Pemigatinib Versus Chemotherapy in Unresectable or Metastatic Cholangiocarcinoma
NCT03773302	Phase 3	TERMINATED	Phase 3 Study of BGJ398 (Oral Infigratinib) in First Line Cholangiocarcinoma With FGFR2 Gene Fusions/Translocations
NCT03779035	Phase 3	UNKNOWN	Adjuvant Chemotherapy for Biliary Tract Cancer After Curative Resection
NCT04093362	Phase 3	TERMINATED	Futibatinib Versus Gemcitabine-Cisplatin Chemotherapy as First-Line Treatment of Patients With Advanced Cholangiocarcinoma Harboring FGFR2 Gene Rearrangements
NCT04157985	Phase 3	COMPLETED	Evaluating Length of Treatment With PD-1/PD-L1 Inhibitor in Advanced Solid Tumors
NCT05823311	Phase 3	RECRUITING	Lenvatinib, Tislelizumab Combined with Gemcitabine and Cisplatin (GPLET) in the Treatment of Advanced Cholangiocarcinoma
NCT05876754	Phase 3	ACTIVE_NOT_RECRUITING	An Early Access Study of Ivosidenib in Patients With a Pretreated Locally Advanced or Metastatic Cholangiocarcinoma
NCT05948475	Phase 3	ACTIVE_NOT_RECRUITING	Study of Tinengotinib VS. Physician’s Choice a Treatment of Subjects With FGFR-altered in Cholangiocarcinoma
NCT07155525	Phase 3	RECRUITING	Tissue Adhesive Glue Modified Cyanoacrylate (Glubran® 2) in Soft Pancreas
NCT07328919	Phase 3	NOT_YET_RECRUITING	Efficacy and Safety of TT-00420 (Tinengotinib) Tablets Versus Chemotherapy in Patients With Advanced Intrahepatic Cholangiocarcinoma Harboring FGFR2 Fusions/Rearrangements or Mutations
NCT02871778	Phase 2	COMPLETED	Clearing Lungs With ENaC Inhibition in Primary Ciliary Dyskinesia
NCT07318974	Phase 2	ACTIVE_NOT_RECRUITING	Melatonin Therapy for Improving ICSI Outcomes in Women With Diminished Ovarian Reserve
NCT00055237	Phase 2	COMPLETED	Bevacizumab to Treat Kaposi’s Sarcoma in HIV-Positive and HIV-Negative Patients
NCT00064142	Phase 2	COMPLETED	Halofuginone Hydrobromide in Treating Patients With HIV-Related Kaposi’s Sarcoma
NCT00194467	Phase 2	COMPLETED	Suppression of Oral HHV8 Shedding With Valganciclovir
NCT01067690	Phase 2	COMPLETED	Treatment With Indinavir and Chemotherapy for Advanced Classical Kaposi’s Sarcoma
NCT01276236	Phase 2	COMPLETED	Effects of Maraviroc (MVC) on HIV-related Kaposi’s Sarcoma (KS)
NCT01412515	Phase 2	TERMINATED	A Phase II Study With Tumor Molecular Pharmacodynamic (MPD) Evaluation of Oral mTOR-inhibitor Everolimus (RAD001) 10 mg Daily in Patients Suffering From Classic or Endemic Kaposi’s Sarcoma
NCT01419561	Phase 2	RECRUITING	Natural History Study of the KSHV Inflammatory Cytokine Syndrome (KICS)
NCT02029430	Phase 2	COMPLETED	A Study to Investigate ALDOXORUBICIN in HIV-infected Subjects With Kaposi’s Sarcoma
NCT02137564	Phase 2	WITHDRAWN	Gamma Secretase Inhibitor PF-03084014 in Treating Patients With AIDS-Associated Kaposi Sarcoma
NCT02201420	Phase 2	COMPLETED	Evaluation of Tc 99m Tilmanocept Localization in Primary Cutaneous Kaposi’s Sarcoma and Lymphatic Drainage by SPECT/CT
NCT03077451	Phase 2	COMPLETED	Nelfinavir Mesylate in Treating Patients With Kaposi Sarcoma
NCT03296553	Phase 2	COMPLETED	Impact of Valganciclovir on Severe IRIS-Kaposi Sarcoma Mortality: an Open-label, Parallel, Randomized Controlled-trial.
NCT03469804	Phase 2	UNKNOWN	Phase II Multicentric Study of Pembrolizumab in Classic or Endemic Kaposi’s Sarcoma
NCT03993106	Phase 2	UNKNOWN	A Study of sEphB4-HSA in Kaposi Sarcoma
NCT04065152	Phase 2	UNKNOWN	Phase II Multicenter Study of Talimogene Laherparepvec in Classic or Endemic Kaposi Sarcoma
NCT04305691	Phase 2	RECRUITING	Trial of Ixazomib for Kaposi Sarcoma
NCT05329792	Phase 2	UNKNOWN	L19IL2/L19TNF in Skin Cancer Patients
NCT05797662	Phase 2	NOT_YET_RECRUITING	A Study of Propranolol to Treat Kaposi Sarcoma
NCT05846724	Phase 2	WITHDRAWN	Pembrolizumab Plus Lenvatinib in Previously Treated Classic Kaposi Sarcoma
NCT06052618	Phase 2	RECRUITING	Phase II Study of Pacritinib in Kaposi Sarcoma Herpesvirus (KSHV)-Associated Multicentric Castleman Disease and KSHV-Associated Inflammatory Cytokine Syndrome (KICS)
NCT06445166	Phase 2	RECRUITING	Propranolol for the Treatment of Kaposi Sarcoma in Adults
NCT06638931	Phase 2	RECRUITING	Agnostic Therapy in Rare Solid Tumors
NCT07308886	Phase 2	RECRUITING	Recombinant Glycosylated Human Interleukin-7 (CYT107) for the Treatment of Kaposi Sarcoma in Participants With HIV and Immune Non-Response (REGIMENKS HIV)

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for IL6 across ~30M SureChEMBL compounds — explore on Sugi Predict.