IL2

Summary

IL2 (interleukin 2, HGNC:6001) is a protein-coding gene on chromosome 4q27, encoding Interleukin-2 (P60568). Cytokine produced by activated CD4-positive helper T-cells and to a lesser extend activated CD8-positive T-cells and natural killer (NK) cells that plays pivotal roles in the immune response and tolerance.

This gene is a member of the interleukin 2 (IL2) cytokine subfamily which includes IL4, IL7, IL9, IL15, IL21, erythropoietin, and thrombopoietin. The protein encoded by this gene is a secreted cytokine produced by activated CD4+ and CD8+ T lymphocytes, that is important for the proliferation of T and B lymphocytes. The receptor of this cytokine (IL2R) is a heterotrimeric protein complex whose gamma chain is also shared by IL4 and IL7. The expression of this gene in mature thymocytes is monoallelic, which represents an unusual regulatory mode for controlling the precise expression of a single gene. The targeted disruption of a similar gene in mice leads to ulcerative colitis-like disease, which suggests an essential role of this gene in the immune response to antigenic stimuli.

Source: NCBI Gene 3558 — RefSeq curated summary.

At a glance

• GWAS associations: 55 (top 2% of genes corpus-wide)
• Clinical variants (ClinVar): 3 total — 2 pathogenic
• ChEMBL bioactivity: 2 clinical-phase molecules tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.85 (intermediate), LOEUF 0.65 (unconstrained)
• MANE Select transcript: NM_000586

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6001
Approved symbol	IL2
Name	interleukin 2
Location	4q27
Locus type	gene with protein product
Status	Approved
Aliases	IL-2, TCGF
Ensembl gene	ENSG00000109471
Ensembl biotype	protein_coding
OMIM	147680
Entrez	3558

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 retained_intron

MANE Select: ENST00000226730

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

ENST00000226730, ENST00000477645

RefSeq mRNA: 1 — MANE Select: NM_000586 NM_000586

CCDS: CCDS3726

Canonical transcript exons

ENST00000226730 — 4 exons

Exon	Start	End
ENSE00000935280	122456144	122456203
ENSE00001138256	122451470	122451862
ENSE00001293064	122456294	122456725
ENSE00003641080	122453710	122453853

Expression profiles

Bgee: expression breadth broad, 92 present calls, max score 84.25.

Highest expression (Bgee): primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, buccal mucosa cell, endometrium epithelium, frontal pole.

Genetic regulation across tissues (GTEx eQTL / sQTL)

IL2 is not an eGene in any GTEx v10 tissue: no tissue shows a variant significantly associated with its expression or splicing (q < 0.05).

Top tissues by expression

showing 100 of 255 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.25	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.10	gold quality
buccal mucosa cell	CL:0002336	68.91	gold quality
endometrium epithelium	UBERON:0004811	59.26	gold quality
frontal pole	UBERON:0002795	56.64	gold quality
lymph node	UBERON:0000029	55.03	gold quality
vermiform appendix	UBERON:0001154	54.05	gold quality
lower esophagus mucosa	UBERON:0035834	52.98	gold quality
small intestine Peyer’s patch	UBERON:0003454	52.02	gold quality
granulocyte	CL:0000094	51.98	gold quality
caecum	UBERON:0001153	50.95	gold quality
small intestine	UBERON:0002108	50.64	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
rectum	UBERON:0001052	50.26	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality
quadriceps femoris	UBERON:0001377	49.95	gold quality
metanephric glomerulus	UBERON:0004736	49.61	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
vastus lateralis	UBERON:0001379	49.27	gold quality
cerebellar vermis	UBERON:0004720	49.25	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
epithelial cell of pancreas	CL:0000083	48.87	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
oviduct epithelium	UBERON:0004804	48.53	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
kidney epithelium	UBERON:0004819	48.11	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
cervix epithelium	UBERON:0004801	48.04	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality
thymus	UBERON:0002370	47.87	gold quality
mucosa of urinary bladder	UBERON:0001259	47.80	gold quality
nephron tubule	UBERON:0001231	47.30	gold quality
diaphragm	UBERON:0001103	47.05	gold quality
deltoid	UBERON:0001476	47.04	gold quality
gluteal muscle	UBERON:0002000	47.03	gold quality
triceps brachii	UBERON:0001509	47.01	gold quality
pancreatic ductal cell	CL:0002079	46.57	silver quality
lower lobe of lung	UBERON:0008949	46.40	silver quality
duodenum	UBERON:0002114	46.25	gold quality
layer of synovial tissue	UBERON:0007616	45.76	gold quality
nasal cavity epithelium	UBERON:0005384	45.61	gold quality
ileal mucosa	UBERON:0000331	45.12	silver quality
gall bladder	UBERON:0002110	44.57	gold quality
spleen	UBERON:0002106	43.95	gold quality
right lung	UBERON:0002167	43.73	gold quality
skin of hip	UBERON:0001554	43.68	silver quality
skeletal muscle tissue	UBERON:0001134	43.67	gold quality
omental fat pad	UBERON:0010414	43.65	gold quality
peritoneum	UBERON:0002358	43.64	gold quality
adipose tissue of abdominal region	UBERON:0007808	43.48	gold quality
squamous epithelium	UBERON:0006914	43.42	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
uterine cervix	UBERON:0000002	43.36	silver quality
bone marrow	UBERON:0002371	43.34	silver quality
epithelium of esophagus	UBERON:0001976	42.87	gold quality
epithelium of bronchus	UBERON:0002031	42.81	gold quality
bronchus	UBERON:0002185	42.69	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
bone marrow cell	CL:0002092	42.13	gold quality
cartilage tissue	UBERON:0002418	42.04	gold quality
fallopian tube	UBERON:0003889	41.61	gold quality
right coronary artery	UBERON:0001625	41.43	silver quality
lung	UBERON:0002048	41.41	silver quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
tonsil	UBERON:0002372	41.31	gold quality
epithelium of mammary gland	UBERON:0003244	41.17	gold quality
embryo	UBERON:0000922	41.13	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
trachea	UBERON:0003126	41.02	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
amniotic fluid	UBERON:0000173	40.69	gold quality
upper lobe of lung	UBERON:0008948	40.61	gold quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
biceps brachii	UBERON:0001507	40.57	gold quality
dorsal plus ventral thalamus	UBERON:0001897	40.56	gold quality
left uterine tube	UBERON:0001303	40.53	gold quality
epithelium of nasopharynx	UBERON:0001951	40.45	gold quality
gingival epithelium	UBERON:0001949	40.43	gold quality
germinal epithelium of ovary	UBERON:0001304	40.33	gold quality
pleura	UBERON:0000977	40.29	gold quality
esophagus squamous epithelium	UBERON:0006920	40.29	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	40.27	gold quality
upper lobe of left lung	UBERON:0008952	40.20	gold quality
jejunum	UBERON:0002115	40.18	gold quality
tongue	UBERON:0001723	40.09	gold quality
urinary bladder	UBERON:0001255	40.06	gold quality
mammary duct	UBERON:0001765	39.98	gold quality
colonic mucosa	UBERON:0000317	39.95	gold quality
mucosa of sigmoid colon	UBERON:0004993	39.95	gold quality
saphenous vein	UBERON:0007318	39.83	gold quality
right uterine tube	UBERON:0001302	39.82	silver quality
parotid gland	UBERON:0001831	39.81	gold quality
oocyte	CL:0000023	39.80	gold quality
urethra	UBERON:0000057	39.80	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-HCAD-29	no	52565.79
E-ANND-3	no	2.20

HPA expression

RNA tissue specificity: Not detected

12 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Rectum	tissue	0.3
Tonsil	tissue	0.3
Lymph node	tissue	0.2
Small intestine	tissue	0.2
Thymus	tissue	0.2
Cervix	tissue	0.1
Pons	tissue	0.1
Esophagus	tissue	0.1
Gallbladder	tissue	0.1
Duodenum	tissue	0.1
Bone marrow	tissue	0.1
Appendix	tissue	0.1

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets:

Target	Regulation
NAB2	Activation
TNFSF10	Repression

Upstream regulators (CollecTRI, top): AGO1, AGO2, AP1, AR, BACH2, BATF3, BCL11B, BCL3, BCL6, BCL6B, BHLHE40, CEBPB, CREB1, CREB3, CREM, CTBP2, EGR1, EGR4, ELF1, EOMES, ESR1, ETS1, ETS2, FOS, FOSB, FOSL1, FOSL2, FOXC1, FOXK2, FOXN1, FOXO3, FOXP1, FOXP3, GABPA, GFI1, GLI3, HAND1, HAND2, HBP1, HDAC1

miRNA regulators (miRDB)

Targeting IL2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 41 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-3913-5P	99.78	67.26	968
HSA-MIR-190A-5P	99.54	71.45	933
HSA-MIR-190B-5P	99.54	71.40	925
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-543	99.52	69.03	2595
HSA-MIR-3122	99.50	66.33	821
HSA-MIR-6513-5P	99.43	67.81	1071
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-374A-3P	98.87	67.82	1531
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-887-5P	98.82	65.90	1347

Functional genomics

gnomAD constraint: pLI 0.847, LOEUF 0.645, missense Z 1.15 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000226730 — one region, missense o/e 0.73.

Literature-anchored findings (GeneRIF, showing 40)

• Primary T lymphocytes that exhibit avid specific melanoma antigen and tumor recognition can be retrovirally transduced, produce IL-2 and grow for over 8 weeks in the absence of IL-2, upon restimulation. (PMID:11714800)
• kinetic mechanism of basal transcription at the IL-2 promoter using a human in vitro RNA polymerase II transcription system (PMID:11743717)
• IL-2 plays an important and complex role in the immune system, serving as a growth factor, a differentiation factor, and a regulator of cell death. (PMID:11826762)
• role in regulation of Toll-like receptor surface expression in human peripheral blood monocytes and B cells (PMID:11841848)
• Molecular mechanism of NFAT family proteins for differential regulation of the IL-2 and TNF-alpha promoters. (PMID:11911478)
• recombinant IL-2 treatment decreases P-glycoprotein activity and paclitaxel metabolism (PMID:11914641)
• The in situ detection of interleukin-2 and interleukin-2 receptor (IL-2R) has been documented in perinatal white matter lesions associated with periventricular leukomalacia. (PMID:11940709)
• effect of hla-dr matching on acute rejection after heart transplantation influenced by il-2 polymorphism (PMID:11981437)
• IL-2 directly affects NK cell migratory ability in vitro by rapid and direct down-regulation of chemokine receptor CXCR3 mRNA expression, a decrease associated with a significant reduction in chemotaxis in the presence of IFN-gamma-inducible protein-10. (PMID:12055219)
• increased HIV replication in the thymus by inducing differentiation and expansion of mature CD27(+) thymocytes expressing CXCR4 or CCR5 (PMID:12072494)
• B-CLL patients with progressive disease had a significantly increased number of T cells spontaneously producing IL-2, IL-4 and GM-CSF, suggesting a role for T cells in the pathogenesis of B-CLL. (PMID:12144536)
• Elevated IL-2 and IL-2 receptor serum levels correlated with the severity of cutaneous graft-versus-host disease after bone marrow transplantation, and evidence suggested that both act together in the development of cutaneous GVHD. (PMID:12171778)
• IL-2 transcription in Jurkat cells is stimulated by a T cell receptor/DOCK2/Rac2 signal transduction pathway (PMID:12176041)
• The proximal promoter region of the IL-2 gene can assemble into a rotationally and translationally positioned mononucleosome under chromatin reconstitution conditions in vitro and in vivo, maintaining an inactive IL-2 gene in resting T cells. (PMID:12193716)
• The long-term immunologic effects of IL2 administered to HIV patients, including expansion of T-cell subsets and up-regulation of CD25 expression without increases in expression of the beta and gamma chains of the IL-2 receptor. (PMID:12200381)
• The spectrin-ankyrin skeleton controls CD45 surface display and interleukin-2 production. (PMID:12354383)
• mechanisms of IL-2-mediated prosurvival signaling in NK cells via an Akt-dependent pathway regulated by Syk and Rac1 (PMID:12393431)
• the higher capacity of CTL clones to produce IL-2 on their own seemed to be correlated with the in vivo efficacy for tumor eradication (PMID:12456594)
• hypertonic stress increases T cell interleukin-2 expression through a mechanism that involves ATP release, P2 receptor, and p38 MAPK activation (PMID:12464620)
• CD56+ NK cells exist in lymph nodes & endogenous T-cell-derived IL-2, acting through the NK high-affinity IL-2 receptor, costimulates them to secrete IFN-gamma. This is the 1st evidence of immunoregulation of innate immune lymphocytes by adaptive ones. (PMID:12480696)
• A novel hematopoietic adaptor protein, Chat-H, positively regulates T cell receptor-mediated production of this protein in Jurkat cells. (PMID:12486027)
• Nuclear export of NF90 is required for its interleukin-2 mRNA stabilization. (PMID:12504009)
• IL-2 decreased the expression of ERK2 & increased the expression of ERK3. IL-2 increased the expression of PKCalpha, PKCdelta and PKCepsilon. (PMID:12536241)
• endothelin-1 (ET-1), interleukin-2 (IL-2) and amino-terminal propeptide type III procollagen (PIII NP) can be used as markers for diagnosis of human cases infected with chronic and acute filariasis (PMID:12557940)
• IL2 production is increased by FAP48-FKBP complexes (PMID:12604780)
• no evidence for genetic association conferred by the -384 and 114 IL-2 SNP with respect to susceptibility and severity of rheumatoid arthritis. (PMID:12610796)
• denaturation transitions in the secondary and tertiary structure of IL-2 suggest intermediates and possible relation to ligand binding and endocytic trafficking (PMID:12717025)
• One synthetic fragment consisting of amino acids 22-58 contained 100% of the vasopermeability activity of IL-2 and was designated permeability-enhancing peptide (PEP). (PMID:12759392)
• IL-2 deprivation raises the level of RC3 and other apoptotic factors, which induce apoptosis by increasing the intracellular Ca(2+) concentration (PMID:12808095)
• IL-2 regulates homeostasis by modulating the equilibrium between proliferation and apoptotic cell death in T cells that have recently exited from the thymus as well as mature naive and memory T cell subsets. (PMID:12816983)
• Genotype is associated with kidney transplantation rejection, but not with heart transplantation outcome. (PMID:12826155)
• The mixed leukcyte culture model suggest that allorecognition upregulates IL-2 but not IL-15 expression. (PMID:12826231)
• In all three groups of patients significant correlation was seen between abundance of IL-2 vs. IL-4, IL-5, IL-10, or TNF-alpha, between IL-4 vs. IL-10, and between TNF-alpha vs. INF-gamma (PMID:12851716)
• IL-2 secretion from rat T9.F glioma cells enhances tumorigenesis when the tumor is implanted in the brain; in contrast, IL-2-secreting T9.F glioma cells are completely rejected when implanted in the periphery, resulting in tumor-specific immunity. (PMID:12864971)
• expression of alleles of the genes encoding IL-2, IL-3, IL-4, and IL-13 in CD4(+) T cell clones (PMID:12884288)
• Upon prolonged culture (down phase), human T cells undergo an IL-2-dependent switch from type II signaling to type I signaling cells that renders T cells sensitive to CD95-mediated activation-induced cell death. (PMID:12960316)
• Number of CD8+/IL-2 cells significantly higher in elderly trained than in elderly untrained. (PMID:14499500)
• IL-2 activates not only STAT3, STAT5, the phosphatidylinositol 3-kinase pathway, and extracellular signal-regulated kinase-2 pathway, but also STAT4 as in NK cells, and the p38 mitogen-activated protein kinase pathway as in alpha beta T cells. (PMID:14607923)
• Because IL-2 regulates gene expression through the interactions of transcription factors with IFN-gamma activated sequence and Ets binding site motifs, it is likely that IL-2 influences CD94 gene expression through formation of DNA-protein complexes. (PMID:14607929)
• The development of breast tumour is associated with an increased expression of IL-2 and this expression also seems to be associated with the malignancy of the tumour. (PMID:14680494)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Il2	ENSMUSG00000027720
rattus_norvegicus	Il2	ENSRNOG00000017348

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:96548) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 96 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased T cell proliferation	4
enlarged lymph nodes	3
colitis	3
decreased cytotoxic T cell cytolysis	3
abnormal CD4-positive, alpha-beta T cell physiology	3
increased IgG1 level	3
abnormal intestinal epithelium morphology	2
rectal prolapse	2
anemia	2
abnormal T cell activation	2
premature death	2
abnormal lymphocyte morphology	2
abnormal thymocyte activation	2
decreased T cell proliferation	2
increased B cell proliferation	2
increased CD4-positive, alpha-beta T cell number	2
abnormal CD8-positive, alpha-beta intraepithelial T cell morphology	2
abnormal colon goblet cell morphology	2
abnormal bone marrow cell number	1
decreased hematocrit	1
crypts of Lieberkuhn abscesses	1
intestinal ulcer	1
amyloidosis	1
abnormal salivary gland morphology	1
decreased salivation	1

+71 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
Hylobates lar	P60569	100.0%	Diamond
Macaca nemestrina	P68290	100.0%	Diamond
Macaca mulatta	P68291	100.0%	Diamond
Bubalus kerabau	Q2PE78	100.0%	Diamond
Aotus lemurinus	Q7JFM2	100.0%	Diamond
Aotus nigriceps	Q7JFM3	100.0%	Diamond
Aotus vociferans	Q7JFM4	100.0%	Diamond
Aotus nancymaae	Q7JFM5	100.0%	Diamond
Bubalus bubalis	Q95KP3	100.0%	Diamond
Papio hamadryas	Q9XS38	100.0%	Diamond
Cercocebus atys	P46649	99.4%	Diamond
Vulpes vulpes	Q25BC3	99.4%	Diamond
Canis lupus familiaris	Q29416	99.4%	Diamond
Papio anubis	Q865Y1	99.4%	Diamond
Saimiri sciureus	Q8MKH2	99.4%	Diamond
Macaca fascicularis	Q29615	98.7%	Diamond
Camelus bactrianus	Q2PE47	98.7%	Diamond
Lama glama	Q865X2	98.7%	Diamond
Bos taurus	P05016	98.1%	Diamond
Boselaphus tragocamelus	Q4U313	98.1%	Diamond
Ovis aries	P19114	97.4%	Diamond
Moschus berezovskii	Q5MBA8	96.8%	Diamond
Mus spretus	Q08867	96.4%	Diamond
Orcinus orca	O97513	94.7%	Diamond
Delphinapterus leucas	Q9XT84	94.7%	Diamond
Mirounga angustirostris	O62641	94.2%	Diamond
Halichoerus grypus	Q9XT83	94.2%	Diamond
Capra hircus	P36835	91.0%	Diamond
Ailuropoda melanoleuca	Q5PXD0	90.3%	Diamond
Felis catus	Q07885	89.0%	Diamond
Cervus elaphus	P51747	86.4%	Diamond
Sus scrofa	P26891	83.8%	Diamond
Oryctolagus cuniculus	O77620	80.1%	Diamond
Meriones unguiculatus	Q08081	79.4%	Diamond
Dasypus novemcinctus	Q1WM29	75.5%	Diamond
Equus caballus	P37997	75.3%	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
ADAD1	protein-coding	132612
BBS12	protein-coding	166379
IL21	protein-coding	59067
IL21-AS1	ncRNA	100996941
BLTP1	protein-coding	84162
FGF2	protein-coding	2247

Protein

Protein identifiers

Interleukin-2 — P60568 (reviewed: P60568)

Alternative names: T-cell growth factor

All UniProt accessions (2): P60568, Q0GK43

UniProt curated annotations — full annotation on UniProt →

Function. Cytokine produced by activated CD4-positive helper T-cells and to a lesser extend activated CD8-positive T-cells and natural killer (NK) cells that plays pivotal roles in the immune response and tolerance. Binds to a receptor complex composed of either the high-affinity trimeric IL-2R (IL2RA/CD25, IL2RB/CD122 and IL2RG/CD132) or the low-affinity dimeric IL-2R (IL2RB and IL2RG). Interaction with the receptor leads to oligomerization and conformation changes in the IL-2R subunits resulting in downstream signaling starting with phosphorylation of JAK1 and JAK3. In turn, JAK1 and JAK3 phosphorylate the receptor to form a docking site leading to the phosphorylation of several substrates including STAT5. This process leads to activation of several pathways including STAT, phosphoinositide-3-kinase/PI3K and mitogen-activated protein kinase/MAPK pathways. Functions as a T-cell growth factor and can increase NK-cell cytolytic activity as well. Promotes strong proliferation of activated B-cells and subsequently immunoglobulin production. Plays a pivotal role in regulating the adaptive immune system by controlling the survival and proliferation of regulatory T-cells, which are required for the maintenance of immune tolerance. Moreover, participates in the differentiation and homeostasis of effector T-cell subsets, including Th1, Th2, Th17 as well as memory CD8-positive T-cells.

Subcellular location. Secreted.

Disease relevance. A chromosomal aberration involving IL2 is found in a form of T-cell acute lymphoblastic leukemia (T-ALL). Translocation t(4;16)(q26;p13) with involves TNFRSF17.

Similarity. Belongs to the IL-2 family.

RefSeq proteins (1): NP_000577* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000779	IL-2	Family
IPR009079	4_helix_cytokine-like_core	Homologous_superfamily
IPR030477	IL-2_CS	Conserved_site

Pfam: PF00715

UniProt features (23 total): helix 13, strand 4, sequence variant 2, signal peptide 1, chain 1, glycosylation site 1, disulfide bond 1

Structure

Experimental structures (PDB)

showing 30 of 38 structures by resolution:

PDB	Title	Method	Resolution (Å)
8SOZ	Structure of the complex formed by human interleukin-2 and scFv 602	X-RAY DIFFRACTION	1.64
8SOW	Structure of the complex formed by human interleukin-2 and scFv F10	X-RAY DIFFRACTION	1.71
7M2G	INTERLEUKIN-2 (human) mutant P65K, C125S	X-RAY DIFFRACTION	1.79
4NEJ	Small molecular fragment bound to crystal contact interface of Interleukin-2	X-RAY DIFFRACTION	1.92
4NEM	Small molecular fragment bound to crystal contact interface of Interleukin-2	X-RAY DIFFRACTION	1.93
1M48	Crystal Structure of Human IL-2 Complexed with …	X-RAY DIFFRACTION	1.95
5LQB	Complex structure of human IL2 mutant, Proleukin, with Fab fragment of NARA1 antibody	X-RAY DIFFRACTION	1.95
1M47	Crystal Structure of Human Interleukin-2	X-RAY DIFFRACTION	1.99
1M49	Crystal Structure of Human Interleukin-2 Complexed with SP-1985	X-RAY DIFFRACTION	2
1M4B	Crystal Structure of Human Interleukin-2 K43C Covalently Modified at C43 with …	X-RAY DIFFRACTION	2.15
1M4A	Crystal Structure of Human Interleukin-2 Y31C Covalently Modified at C31 with …	X-RAY DIFFRACTION	2.18
1NBP	Crystal Structure Of Human Interleukin-2 Y31C Covalently Modified At C31 With …	X-RAY DIFFRACTION	2.2
7RA9	Designed StabIL-2 seq1	X-RAY DIFFRACTION	2.2
2B5I	cytokine receptor complex	X-RAY DIFFRACTION	2.3
5M5E	Crystal structure of a interleukin-2 variant in complex with interleukin-2 receptor	X-RAY DIFFRACTION	2.3
1M4C	Crystal Structure of Human Interleukin-2	X-RAY DIFFRACTION	2.4
7DR4	Complex of anti-human IL-2 antibody and human IL-2	X-RAY DIFFRACTION	2.49
3INK	UNRAVELING THE STRUCTURE OF INTERLEUKIN-2: REPLY	X-RAY DIFFRACTION	2.5
1PW6	Low Micromolar Small Molecule Inhibitor of IL-2	X-RAY DIFFRACTION	2.6
7YZJ	FAB IN COMPLEX WITH ANTIGENIC PEPTIDE OF INTERLEUKIN-2	X-RAY DIFFRACTION	2.6
7RAA	Designed StabIL-2 seq15	X-RAY DIFFRACTION	2.69
1QVN	Structure of SP4160 Bound to IL-2 V69A	X-RAY DIFFRACTION	2.7
5UTZ	Human IL-2/Fab complex	X-RAY DIFFRACTION	2.75
1PY2	Structure of a 60 nM Small Molecule Bound to a Hot Spot on IL-2	X-RAY DIFFRACTION	2.8
1Z92	structure of interleukin-2 with its alpha receptor	X-RAY DIFFRACTION	2.8
6YE3	IL-2 in complex with a Fab fragment from UFKA-20	X-RAY DIFFRACTION	2.89
9KMC	Cryo-EM structure of the heterotrimeric interleukin-2 receptor in complex with …	ELECTRON MICROSCOPY	2.97
2ERJ	Crystal structure of the heterotrimeric interleukin-2 receptor in complex with …	X-RAY DIFFRACTION	3
3QB1	Interleukin-2 mutant D10	X-RAY DIFFRACTION	3.1
6LX3	Cryo-EM structure of human secretory immunoglobulin A	ELECTRON MICROSCOPY	3.15

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P60568-F1	84.68	0.60

Antibody-complex structures (SAbDab)

8 antibodies co-crystallized with this protein: 5LQB, 5UTZ, 6YE3, 7DR4, 7YZJ, 8SOW, 8SOZ, 9KMC

Human Protein Atlas

Protein class: Predicted secreted proteins, Plasma proteins, Cancer-related genes, Candidate cancer biomarkers, Candidate cardiovascular disease genes, Disease related genes, Human disease related genes, Diabetes

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH uncertain

Functional residue map

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

Disulfide bonds (1)

Type	Positions
Disulfide bond	78–125

Glycosylation sites (1)

Type	Positions
O-linked (galnac…) threonine	23

Function

Pathways and Gene Ontology

Reactome pathways

4 curated (TAS) of 16; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

16 pathways:

ID	Pathway	Evidence
R-HSA-912526	Interleukin receptor SHC signaling	curated
R-HSA-9020558	Interleukin-2 signaling	curated
R-HSA-5673001	RAF/MAP kinase cascade	curated
R-HSA-8877330	RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs)	curated
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-451927	Interleukin-2 family signaling	—
R-HSA-512988	Interleukin-3, Interleukin-5 and GM-CSF signaling	—
R-HSA-5683057	MAPK family signaling cascades	—
R-HSA-5684996	MAPK1/MAPK3 signaling	—
R-HSA-73857	RNA Polymerase II Transcription	—
R-HSA-162582	Signal Transduction	—
R-HSA-449147	Signaling by Interleukins	—
R-HSA-8878171	Transcriptional regulation by RUNX1	—

MSigDB gene sets: 440 (showing top): PID_SHP2_PATHWAY, GOBP_DENDRITE_DEVELOPMENT, GOBP_REGULATION_OF_CELL_ACTIVATION, RNGTGGGC_UNKNOWN, REACTOME_INTERLEUKIN_2_FAMILY_SIGNALING, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_DNA_RECOMBINATION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_RESPONSE_TO_ETHANOL, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_REGULATION_OF_ALPHA_BETA_T_CELL_ACTIVATION, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, PID_TELOMERASE_PATHWAY

GO Biological Process (35): adaptive immune response (GO:0002250), leukocyte activation involved in immune response (GO:0002366), positive regulation of immunoglobulin production (GO:0002639), negative regulation of B cell apoptotic process (GO:0002903), immune response (GO:0006955), cell adhesion (GO:0007155), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), positive regulation of cytosolic calcium ion concentration (GO:0007204), cell surface receptor signaling pathway via JAK-STAT (GO:0007259), cell-cell signaling (GO:0007267), positive regulation of cell population proliferation (GO:0008284), natural killer cell activation (GO:0030101), T cell differentiation (GO:0030217), positive regulation of cell growth (GO:0030307), positive regulation of B cell proliferation (GO:0030890), positive regulation of interleukin-17 production (GO:0032740), positive regulation of tissue remodeling (GO:0034105), interleukin-2-mediated signaling pathway (GO:0038110), positive regulation of activated T cell proliferation (GO:0042104), negative regulation of apoptotic process (GO:0043066), response to ethanol (GO:0045471), positive regulation of regulatory T cell differentiation (GO:0045591), positive regulation of inflammatory response (GO:0050729), positive regulation of dendritic spine development (GO:0060999), positive regulation of leukocyte proliferation (GO:0070665), cell surface receptor signaling pathway via STAT (GO:0097696), positive regulation of plasma cell differentiation (GO:1900100), response to tacrolimus (GO:1901327), positive regulation of leukocyte differentiation (GO:1902107), negative regulation of T-helper 17 cell differentiation (GO:2000320), immune system process (GO:0002376), G protein-coupled receptor signaling pathway (GO:0007186), positive regulation of T cell proliferation (GO:0042102), positive regulation of T cell differentiation (GO:0045582), positive regulation of lymphocyte differentiation (GO:0045621)

GO Molecular Function (8): cytokine activity (GO:0005125), interleukin-2 receptor binding (GO:0005134), growth factor activity (GO:0008083), kinase activator activity (GO:0019209), carbohydrate binding (GO:0030246), kappa-type opioid receptor binding (GO:0031851), glycosphingolipid binding (GO:0043208), protein binding (GO:0005515)

GO Cellular Component (1): extracellular region (GO:0005576)

Reactome top-level categories

12 top-level categories:

Category	Pathways
Interleukin-2 family signaling	2
Signaling by Interleukins	2
MAPK1/MAPK3 signaling	1
Transcriptional regulation by RUNX1	1
Interleukin-3, Interleukin-5 and GM-CSF signaling	1
Immune System	1
RNA Polymerase II Transcription	1
Cytokine Signaling in Immune system	1
Signal Transduction	1
MAPK family signaling cascades	1
Gene expression (Transcription)	1
Generic Transcription Pathway	1

GO top-level categories

56 GO namespaces:

Category	Terms
immune response	2
positive regulation of cellular process	2
receptor ligand activity	2
binding	2
cell activation involved in immune response	1
leukocyte activation	1
immunoglobulin production	1
regulation of immunoglobulin production	1
positive regulation of production of molecular mediator of immune response	1
B cell apoptotic process	1
regulation of B cell apoptotic process	1
negative regulation of lymphocyte apoptotic process	1
immune system process	1
response to stimulus	1
cellular process	1
G protein-coupled receptor signaling pathway	1
phospholipase C activator activity	1
regulation of biological quality	1
cell surface receptor signaling pathway via STAT	1
cell communication	1
signaling	1
cell population proliferation	1
regulation of cell population proliferation	1
lymphocyte activation	1
lymphocyte differentiation	1
T cell activation	1
regulation of cell growth	1
cell growth	1
positive regulation of growth	1
regulation of B cell proliferation	1
B cell proliferation	1
positive regulation of lymphocyte proliferation	1
positive regulation of B cell activation	1
positive regulation of cytokine production	1
interleukin-17 production	1
regulation of interleukin-17 production	1
regulation of tissue remodeling	1
tissue remodeling	1
positive regulation of multicellular organismal process	1
cytokine-mediated signaling pathway	1
cellular response to interleukin-2	1
positive regulation of T cell proliferation	1
regulation of activated T cell proliferation	1
activated T cell proliferation	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
cytokine receptor binding	1
growth factor receptor binding	1
enzyme activator activity	1
kinase activity	1
kinase regulator activity	1
opioid receptor binding	1
sphingolipid binding	1
glycolipid binding	1
cellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 11 of 45 annotations. The rest are phylogenetic / computational / electronic (IEA).

11 experimentally-supported GO terms:

GO term	NS	Evidence
cell surface receptor signaling pathway via STAT	BP	direct assay
interleukin-2-mediated signaling pathway	BP	direct assay
leukocyte activation involved in immune response	BP	direct assay
negative regulation of B cell apoptotic process	BP	direct assay
positive regulation of B cell proliferation	BP	direct assay
positive regulation of activated T cell proliferation	BP	direct assay
positive regulation of immunoglobulin production	BP	genetic interaction
positive regulation of interleukin-17 production	BP	direct assay
positive regulation of plasma cell differentiation	BP	genetic interaction
cytokine activity	MF	direct assay
interleukin-2 receptor binding	MF	direct assay

Protein interactions and networks

IntAct

Human interaction partners of IL2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

3 partners by confidence:

Partner	Interaction type	MIscore	Records
IL2RB	direct interaction	0.740	3
IL2RA	physical association	0.670	3
IL17A	association	0.530	2

BioGRID (7 interactions; top human partners by supporting records): IL17A (Affinity Capture-MS; 3 records), CFTR (Affinity Capture-MS), IL2RA (Reconstituted Complex), IL2RG (Affinity Capture-Western), S100A6 (Reconstituted Complex)

SIGNOR signaling

8 signaling interactions:

A	Effect	B	Mechanism
IL2	up-regulates	IL2RA	binding
IL2	up-regulates	IL2RB	binding
IL2	up-regulates	IL2RG	binding
IL2	“up-regulates quantity by expression”	NAB2	“transcriptional regulation”
IL2	“down-regulates quantity by repression”	TNFSF10	“transcriptional regulation”
CREM	“down-regulates quantity by repression”	IL2	“transcriptional regulation”
NFATC1	“up-regulates quantity by expression”	IL2	“transcriptional regulation”
TBX21	“down-regulates quantity by repression”	IL2	“transcriptional regulation”

Protein complexes (CORUM) (2)

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

2 complexes by size:

Complex	Subunits	Members
★ IL-2 receptor-IL-2 complex, high affinity	4	IL2, IL2RA, IL2RB, IL2RG
★ IL-2 receptor-IL-2 complex, intermediate affinity	3	IL2RG, IL2, IL2RB

Ligand–receptor pairs (CellPhoneDB) (2)

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

2 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
IL2RA;IL2RB;IL2RG	ligand	Signaling by Interleukin
IL2RB;IL2RG	ligand	Signaling by Interleukin

Disease & clinical

Genetic variants

Variant evidence for IL2: 3 ClinVar records (2 pathogenic / likely pathogenic); 1 PharmGKB clinical annotation; 55 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	0
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (2)

Showing all 2 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
1706620	NM_000586.4(IL2):c.433del (p.Cys145fs)	Pathogenic	no assertion criteria provided	1
1706621	NM_000586.4(IL2):c.134del (p.Ile44_Leu45insTer)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore IL2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 22 predictions of 217):

Position(s)	Effect	Δscore	Sites
4:122451863	acceptor_loss	1.0000
4:122453708–122453709	donor_loss	1.0000	3
4:122453854–122453855	acceptor_loss	1.0000	6
4:122456292–122456293	donor_loss	1.0000	2
4:122451863–122451864	acceptor_loss	0.9900	4
4:122453708	donor_loss	0.9900
4:122456293	donor_loss	0.9900
4:122453709	donor_loss	0.9800
4:122456292–122456293	donor_loss	0.9800	2
4:122451863	acceptor_loss	0.9700

AlphaMissense

140 missense substitutions predicted likely pathogenic (of 1,006 scored), across 45 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
W141	7	0.920	0.984
C78	7	0.854	0.947
D40	7	0.762	0.819
E82	7	0.711	0.843
P67	6	0.783	0.893
C125	6	0.755	0.818
C145	6	0.729	0.901
F137	5	0.862	0.901
F64	5	0.819	0.913
F144	5	0.805	0.903
F62	5	0.772	0.867
M59	5	0.648	0.742
L83	4	0.812	0.961
L76	3	0.920	0.950
S13	3	0.913	0.913
L79	3	0.907	0.938
L86	3	0.890	0.924
L138	3	0.836	0.912
L116	3	0.771	0.937
L90	3	0.765	0.896

HPA cancer prognostics

RNA cancer specificity: Not detected

Disease associations

OMIM: gene MIM:147680 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): breast neoplasm (MONDO:0021100)

GWAS associations

showing 30 of 55 associations:

Study	Trait	p-value
GCST90002381_68	Eosinophil count	1e-40
GCST005523_20	Celiac disease	2e-38
GCST007800_24	Asthma (childhood onset)	6e-36
GCST000612_34	Celiac disease	2e-27
GCST010984_33	Allergic disease (asthma, hay fever and/or eczema) (multivariate analysis)	5e-22
GCST007798_127	Asthma	2e-21
GCST009720_20	Asthma	5e-20
GCST007798_128	Asthma	2e-18
GCST010985_53	Allergic disease (asthma, hay fever and/or eczema) (age of onset)	2e-17
GCST006409_9	Allergic rhinitis	3e-15
GCST008916_14	Asthma	4e-15
GCST000048_2	Celiac disease	1e-14
GCST007941_6	Medication use (adrenergics, inhalants)	2e-14
GCST007995_16	Asthma (childhood onset)	2e-14
GCST005038_51	Allergic disease (asthma, hay fever or eczema)	5e-14
GCST009798_86	Asthma	5e-14
GCST004030_4	Primary sclerosing cholangitis	1e-13
GCST000157_8	Celiac disease	3e-13
GCST001725_79	Inflammatory bowel disease	3e-13
GCST000392_21	Type 1 diabetes	5e-13
GCST005536_42	Type 1 diabetes	6e-13
GCST006670_7	Primary sclerosing cholangitis	9e-13
GCST008916_50	Asthma	1e-12
GCST007564_23	Asthma or allergic disease (pleiotropy)	3e-12
GCST009798_70	Asthma	8e-12
GCST002520_7	Celiac disease	3e-11
GCST003990_11	Allergy	4e-11
GCST005528_6	Juvenile idiopathic arthritis (oligoarticular or rheumatoid factor-negative polyarticular)	6e-11
GCST007799_46	Asthma (adult onset)	2e-10
GCST007563_2	Allergic disease (asthma, hay fever or eczema)	4e-10

EFO canonical traits (from GWAS)

6 canonical traits:

EFO ID	Trait name
EFO:0005298	allergic sensitization measurement
EFO:0008316	vaso-occlusive pain measurement
EFO:0004847	age at onset
EFO:1002011	adult onset asthma
EFO:0009941	Inhalant adrenergic use measurement
EFO:0004842	eosinophil count

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D001943	Breast Neoplasms	C04.588.180; C17.800.090.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5880 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 8,809 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

2 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL395414	DISOGLUSIDE	2	251
CHEMBL242341	FORMONONETIN	2	8,558

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

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

Variant	Association	Level	Drugs	Phenotypes
rs6822844	Efficacy	3	rituximab	Systemic lupus erythematosus

PharmGKB variants

1 variants:

Variant	Genes	Level	Score	#Clin annots	Drugs
rs6822844	IL2	3	4.75	1	rituximab

PharmGKB variant annotations

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

4 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs6822844	rituximab	Efficacy	Genotype GG is associated with increased response to rituximab in people with Lupus Erythematosus, Systemic as compared to genotype GT.	PMID:23645042
rs6822844	rituximab	Efficacy	Genotype GG is associated with increased response to rituximab in people with Autoimmune Diseases as compared to genotype GT.	PMID:23645042
rs2069762	opioids	Dosage	Genotype AA is associated with increased dose of opioids in people with Pain and Neoplasms as compared to genotypes AC + CC.	PMID:38126330
rs2069762	morphine	Toxicity	Genotypes AC + CC is associated with decreased likelihood of Nausea, Fatigue or Depression when treated with morphine in people with Pain and Neoplasms as compared to genotype AA.	PMID:38824169

Binding affinities (BindingDB)

252 measured of 587 human assays (589 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEBI:74020	KD	0.029 nM
CHEMBL5081901	EC50	0.609 nM
CHEMBL3289607	KD	2.59 nM
5-[2-chloro-5-(trifluoromethyl)phenyl]-N-(2,6-difluorophenyl)thiophene-2-carboxamide	IC50	3 nM	US-8802721: Thiophene compounds for inflammation and immune-related uses
methyl 3-[5-[(2,6-difluorophenyl)carbamoyl]thiophen-2-yl]-4-methylbenzoate	IC50	6.4 nM	US-8802721: Thiophene compounds for inflammation and immune-related uses
US10399967, Compound 98	IC50	8 nM	US-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 108	IC50	8 nM	US-10399967: Compounds for inflammation and immune-related uses
CHEMBL4857063	IC50	8 nM
US10399967, Compound 22	IC50	9 nM	US-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 73	IC50	9 nM	US-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 75	IC50	9 nM	US-10399967: Compounds for inflammation and immune-related uses
CHEMBL5205694	EC50	9.4 nM
US10399967, Compound 71	IC50	10 nM	US-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 72	IC50	10 nM	US-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 109	IC50	10 nM	US-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 112	IC50	10 nM	US-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 122	IC50	10 nM	US-10399967: Compounds for inflammation and immune-related uses
(2S)-N-[2-[(4aS,5aR)-5,5-difluoro-5a-methyl-1,4,4a,6-tetrahydrocyclopropa[f]indazol-3-yl]-6-methyl-1H-benzimidazol-5-yl]-N-methyl-2-morpholin-4-ylpropanamide	IC50	10 nM	US-11661419: Benzimidazole derivative compounds and uses thereof
US10399967, Compound 70	IC50	11 nM	US-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 77	IC50	11 nM	US-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 81	IC50	11 nM	US-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 99	IC50	11 nM	US-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 114	IC50	11 nM	US-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 121	IC50	11 nM	US-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 7	IC50	12 nM	US-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 17	IC50	12 nM	US-10399967: Compounds for inflammation and immune-related uses
N-(5-(2-chloro-5- cyclopropoxyphenyl)pyrazin-2-yl)-4- methylnicotinamide	IC50	12 nM	US-10399967: Compounds for inflammation and immune-related uses
CHEMBL5560228	EC50	12 nM
US10399967, Compound 14	IC50	13 nM	US-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 76	IC50	13 nM	US-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 90	IC50	13 nM	US-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 144	IC50	13 nM	US-10399967: Compounds for inflammation and immune-related uses
(2R)-N-[2-[(4aS,5aR)-5a-methyl-4,4a,5,6-tetrahydro-1H-cyclopropa[f]indazol-3-yl]-3H-benzimidazol-5-yl]-N-methyl-2-(oxan-4-yl)propanamide	IC50	13 nM	US-11661419: Benzimidazole derivative compounds and uses thereof
5-[2-chloro-5-(trifluoromethyl)phenyl]-N-(3-methyl-4-pyridinyl)thiophene-2-carboxamide	IC50	14 nM	US-8802721: Thiophene compounds for inflammation and immune-related uses
US10399967, Compound 115	IC50	14 nM	US-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 116	IC50	14 nM	US-10399967: Compounds for inflammation and immune-related uses
CHEMBL4869725	IC50	14 nM
US10399967, Compound 103	IC50	16 nM	US-10399967: Compounds for inflammation and immune-related uses
2,6-difluoro-N-[5-[3-(trifluoromethyl)phenyl]thiophen-2-yl]benzamide	IC50	16.5 nM	US-8802721: Thiophene compounds for inflammation and immune-related uses
US10399967, Compound 137	IC50	17 nM	US-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 37	IC50	18 nM	US-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 94	IC50	18 nM	US-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 104	IC50	18 nM	US-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 123	IC50	18 nM	US-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 146	IC50	18 nM	US-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 24	IC50	19 nM	US-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 6	IC50	20 nM	US-10399967: Compounds for inflammation and immune-related uses
US10399967, Compound 83	IC50	20 nM	US-10399967: Compounds for inflammation and immune-related uses
CHEMBL4874500	KD	20 nM
US10399967, Compound 131	IC50	21 nM	US-10399967: Compounds for inflammation and immune-related uses

ChEMBL bioactivities

116 potent at pChembl≥5 of 124 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.54	Kd	0.0289	nM	DISOGLUSIDE
8.59	Kd	2.59	nM	CHEMBL3289607
8.52	IC50	3	nM	CHEMBL3646774
8.19	IC50	6.4	nM	CHEMBL3646776
8.10	IC50	8	nM	CHEMBL4857063
8.03	EC50	9.4	nM	CHEMBL5205694
8.00	IC50	10	nM	CHEMBL5087453
7.96	IC50	11	nM	CHEMBL4868242
7.94	EC50	11.56	nM	CHEMBL5560228
7.89	IC50	13	nM	CHEMBL5090091
7.85	IC50	14	nM	CHEMBL3646775
7.85	IC50	14	nM	CHEMBL4869725
7.78	IC50	16.5	nM	CHEMBL3646778
7.70	Kd	20	nM	GALUTEOLIN
7.60	EC50	25.3	nM	CHEMBL5398436
7.50	IC50	32	nM	CHEMBL4868367
7.47	IC50	34	nM	CHEMBL4848840
7.47	IC50	34	nM	CHEMBL4861512
7.47	IC50	34	nM	CHEMBL5088468
7.45	Kd	35.6	nM	CHEMBL3289608
7.45	EC50	35.2	nM	CHEMBL5404419
7.41	IC50	39	nM	CHEMBL5084598
7.34	EC50	45.37	nM	CHEMBL5557745
7.33	IC50	47	nM	CHEMBL5074957
7.30	IC50	50	nM	CHEMBL4868517
7.26	Kd	54.9	nM	CHEMBL3289611
7.26	IC50	55	nM	CHEMBL4859192
7.23	IC50	58.5	nM	CHEMBL3646777
7.22	IC50	60	nM	CHEMBL429852
7.22	Ki	60	nM	CHEMBL429852
7.19	IC50	64	nM	CHEMBL4859714
7.19	IC50	64.8	nM	CHEMBL4855379
7.16	IC50	69	nM	CHEMBL4854994
7.14	EC50	72.91	nM	CHEMBL5523660
7.11	IC50	78	nM	CHEMBL4872086
7.10	IC50	80	nM	CHEMBL4857666
7.09	IC50	82	nM	CHEMBL5079033
7.06	IC50	87	nM	CHEMBL3646781
7.04	IC50	91	nM	CHEMBL5082562
7.04	EC50	90.4	nM	CHEMBL5558965
7.03	IC50	94.4	nM	CHEMBL4868543
7.02	IC50	94.8	nM	CHEMBL3646780
7.02	IC50	96	nM	CHEMBL5086824
7.01	EC50	97.27	nM	CHEMBL5557243
7.00	Kd	100	nM	CHEMBL429852
6.99	IC50	103.6	nM	CHEMBL3646779
6.96	EC50	108.4	nM	CHEMBL5561221
6.95	IC50	113	nM	CHEMBL5080834
6.92	Kd	120	nM	ONONIN
6.82	IC50	150	nM	CHEMBL4848699

PubChem BioAssay actives

84 with measured affinity, of 160 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2R,3S,4S,5R,6R)-2-(hydroxymethyl)-6-[(1S,2S,4S,5’R,6R,7S,8R,9S,12S,13R,16S)-5’,7,9,13-tetramethylspiro[5-oxapentacyclo[10.8.0.02,9.04,8.013,18]icos-18-ene-6,2’-oxane]-16-yl]oxyoxane-3,4,5-triol	1156797: Binding affinity to IL-2 (unknown origin)	kd	<0.0001	uM
methyl (4S,5Z,6S)-5-ethylidene-4-[2-oxo-2-[[(2R,3S,4S,5R,6R)-3,4,5-trihydroxy-6-[2-(4-hydroxyphenyl)ethoxy]oxan-2-yl]methoxy]ethyl]-6-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-4H-pyran-3-carboxylate	1156797: Binding affinity to IL-2 (unknown origin)	kd	0.0026	uM
N-[4-[2-chloro-5-(trifluoromethyl)phenyl]phenyl]-2,6-difluorobenzamide	1774679: Inhibition of PHA-stimulated IL2 secretion in human Jurkat T cells preincubated for 10 mins followed by PHA addition and measured after 20 to 24 hrs by ELISA	ic50	0.0080	uM
(3S)-6-[[5-[(1R)-1-amino-1-cyclopropylethyl]-8-cyclopropyloxy-2,7-naphthyridin-3-yl]amino]-3-methylspiro[2,3-dihydronaphthalene-4,1’-cyclopropane]-1-one	1884769: Inhibition of IL-2 (unknown origin)	ec50	0.0094	uM
(2S)-N-[2-[(4aS,5aR)-5,5-difluoro-5a-methyl-1,4,4a,6-tetrahydrocyclopropa[f]indazol-3-yl]-6-methyl-1H-benzimidazol-5-yl]-N-methyl-2-morpholin-4-ylpropanamide	1834415: Inhibition of IL-2 in CD3/CD28 activated human CD4+ve Th cells preincubated for 15 mins followed by addition of immuno-cult and measured after 24 hrs by HTRF assay	ic50	0.0100	uM
2,6-difluoro-N-[4-[2-methyl-3-(4-methyl-5-oxo-1,3,4-oxadiazol-2-yl)phenyl]phenyl]benzamide	1774679: Inhibition of PHA-stimulated IL2 secretion in human Jurkat T cells preincubated for 10 mins followed by PHA addition and measured after 20 to 24 hrs by ELISA	ic50	0.0110	uM
3-(3,4-dimethoxyphenyl)-5-[4-(1-methylpiperidin-4-yl)phenyl]-1H-pyrrolo[2,3-b]pyridine	2068006: Activation of IL-2 in human Jurkat cells incubated for 24 hrs by ELISA	ec50	0.0116	uM
(2R)-N-[2-[(4aS,5aR)-5a-methyl-4,4a,5,6-tetrahydro-1H-cyclopropa[f]indazol-3-yl]-3H-benzimidazol-5-yl]-N-methyl-2-(oxan-4-yl)propanamide	1834415: Inhibition of IL-2 in CD3/CD28 activated human CD4+ve Th cells preincubated for 15 mins followed by addition of immuno-cult and measured after 24 hrs by HTRF assay	ic50	0.0130	uM
2-chloro-6-fluoro-N-[4-[2-methyl-3-(4-methyl-5-oxo-1,3,4-oxadiazol-2-yl)phenyl]phenyl]benzamide	1774679: Inhibition of PHA-stimulated IL2 secretion in human Jurkat T cells preincubated for 10 mins followed by PHA addition and measured after 20 to 24 hrs by ELISA	ic50	0.0140	uM
2-(3,4-dihydroxyphenyl)-5-hydroxy-7-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxychromen-4-one	1156797: Binding affinity to IL-2 (unknown origin)	kd	0.0200	uM
N-[1-[(1S)-3-[[6-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]amino]-6-oxohexyl]-methylamino]-1-phenylpropyl]pyrazol-4-yl]-6,6-dimethyl-1,4,5,7-tetrahydroindazole-3-carboxamide;2,2,2-trifluoroacetic acid	2029692: Inhibition of IL-2 in human Jurkat cells pretreated with compound for 4 hrs followed by anti-CD3/CD28 stimulation by ELISA analysis	ec50	0.0253	uM
N-[5-[5-(5,5-dimethyl-4-oxo-1,2-oxazol-3-yl)-2-ethylphenyl]pyrazin-2-yl]-2,6-difluorobenzamide	1774679: Inhibition of PHA-stimulated IL2 secretion in human Jurkat T cells preincubated for 10 mins followed by PHA addition and measured after 20 to 24 hrs by ELISA	ic50	0.0320	uM
N-[2-[(4aS,5aR)-5a-methyl-4,4a,5,6-tetrahydro-1H-cyclopropa[f]indazol-3-yl]-3H-benzimidazol-5-yl]-2,2-difluoro-N-methyl-2-(oxan-4-yl)acetamide	1834415: Inhibition of IL-2 in CD3/CD28 activated human CD4+ve Th cells preincubated for 15 mins followed by addition of immuno-cult and measured after 24 hrs by HTRF assay	ic50	0.0340	uM
N-[5-[5-(5,5-dimethyl-4-oxo-1,2-oxazol-3-yl)-2-methylphenyl]pyrazin-2-yl]-2,6-difluorobenzamide	1774679: Inhibition of PHA-stimulated IL2 secretion in human Jurkat T cells preincubated for 10 mins followed by PHA addition and measured after 20 to 24 hrs by ELISA	ic50	0.0340	uM
2,6-difluoro-N-[4-[2-methyl-5-(4-methyl-5-oxo-1,3,4-oxadiazol-2-yl)phenyl]phenyl]benzamide	1774679: Inhibition of PHA-stimulated IL2 secretion in human Jurkat T cells preincubated for 10 mins followed by PHA addition and measured after 20 to 24 hrs by ELISA	ic50	0.0340	uM
N-[1-[(1S)-3-[4-[2-[1-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]piperidin-4-yl]ethyl]piperazin-1-yl]-1-phenylpropyl]pyrazol-4-yl]-6,6-dimethyl-1,4,5,7-tetrahydroindazole-3-carboxamide;2,2,2-trifluoroacetic acid	2029692: Inhibition of IL-2 in human Jurkat cells pretreated with compound for 4 hrs followed by anti-CD3/CD28 stimulation by ELISA analysis	ec50	0.0352	uM
3-(3-hydroxy-4-methoxyphenyl)-7-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxychromen-4-one	1156797: Binding affinity to IL-2 (unknown origin)	kd	0.0356	uM
(2S)-N-[2-[(4aS,5aR)-5a-methyl-4,4a,5,6-tetrahydro-1H-cyclopropa[f]indazol-3-yl]-6-methyl-1H-benzimidazol-5-yl]-N-methyl-2-morpholin-4-ylpropanamide	1834415: Inhibition of IL-2 in CD3/CD28 activated human CD4+ve Th cells preincubated for 15 mins followed by addition of immuno-cult and measured after 24 hrs by HTRF assay	ic50	0.0390	uM
3-(3,4-dimethoxyphenyl)-5-[4-(oxan-4-yl)phenyl]-1H-pyrrolo[2,3-b]pyridine	2068006: Activation of IL-2 in human Jurkat cells incubated for 24 hrs by ELISA	ec50	0.0454	uM
(2S)-N-[2-[(4aS,5aR)-5a-methyl-4,4a,5,6-tetrahydro-1H-cyclopropa[f]indazol-3-yl]-7-fluoro-6-methyl-3H-benzimidazol-5-yl]-N-methyl-2-morpholin-4-ylpropanamide	1834415: Inhibition of IL-2 in CD3/CD28 activated human CD4+ve Th cells preincubated for 15 mins followed by addition of immuno-cult and measured after 24 hrs by HTRF assay	ic50	0.0470	uM
N-[5-[5-(5,5-dimethyl-4-oxo-1,2-oxazol-3-yl)-2-methoxyphenyl]pyrazin-2-yl]-2,6-difluorobenzamide	1774679: Inhibition of PHA-stimulated IL2 secretion in human Jurkat T cells preincubated for 10 mins followed by PHA addition and measured after 20 to 24 hrs by ELISA	ic50	0.0500	uM
2-cyclohexyl-2-(diaminomethylideneamino)-N-[2-[4-[3-(2,3-dichlorophenyl)-1H-pyrazol-5-yl]piperidin-1-yl]-2-oxoethyl]acetamide	1156797: Binding affinity to IL-2 (unknown origin)	kd	0.0549	uM
N-[5-[3-(5,5-dimethyl-4-oxo-1,2-oxazol-3-yl)-2-methylphenyl]pyrazin-2-yl]-2,6-difluorobenzamide	1774679: Inhibition of PHA-stimulated IL2 secretion in human Jurkat T cells preincubated for 10 mins followed by PHA addition and measured after 20 to 24 hrs by ELISA	ic50	0.0550	uM
5-[[2,3-dichloro-4-[5-[1-[2-[[(2R)-2-(diaminomethylideneamino)-4-methylpentanoyl]amino]acetyl]piperidin-4-yl]-1-methylpyrazol-3-yl]phenoxy]methyl]furan-2-carboxylic acid	318564: Binding affinity to IL2 assessed as inhibition of IL2-IL2Ralpha interaction	ki	0.0600	uM
2,6-difluoro-N-[5-[2-methyl-5-(4-methyl-5-oxo-1,3,4-oxadiazol-2-yl)phenyl]pyrazin-2-yl]benzamide	1774679: Inhibition of PHA-stimulated IL2 secretion in human Jurkat T cells preincubated for 10 mins followed by PHA addition and measured after 20 to 24 hrs by ELISA	ic50	0.0640	uM
2-chloro-N-[5-[5-(5,5-dimethyl-4-oxo-1,2-oxazol-3-yl)-2-methylphenyl]pyrazin-2-yl]-6-fluorobenzamide	1774679: Inhibition of PHA-stimulated IL2 secretion in human Jurkat T cells preincubated for 10 mins followed by PHA addition and measured after 20 to 24 hrs by ELISA	ic50	0.0648	uM
N-[4-[5-(5,5-dimethyl-4-oxo-1,2-oxazol-3-yl)-2-methylphenyl]phenyl]-2,6-difluorobenzamide	1774679: Inhibition of PHA-stimulated IL2 secretion in human Jurkat T cells preincubated for 10 mins followed by PHA addition and measured after 20 to 24 hrs by ELISA	ic50	0.0690	uM
3-(3,4-dimethoxyphenyl)-5-[2-(4-methylpiperazin-1-yl)pyrimidin-5-yl]-1H-pyrrolo[2,3-b]pyridine	2068006: Activation of IL-2 in human Jurkat cells incubated for 24 hrs by ELISA	ec50	0.0729	uM
N-[4-[5-(4-ethyl-5-oxo-1,3,4-oxadiazol-2-yl)-2-methylphenyl]phenyl]-2,6-difluorobenzamide	1774679: Inhibition of PHA-stimulated IL2 secretion in human Jurkat T cells preincubated for 10 mins followed by PHA addition and measured after 20 to 24 hrs by ELISA	ic50	0.0780	uM
N-(4-benzoylphenyl)-8-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]octanamide	1763550: Inhibition of IL2-induced STAT3 phosphorylation in human NK92 cells incubated for 30 mins followed by IL-15 stimulation and measured after 1 hr by alphascreen assay	ic50	0.0800	uM
(2S)-N-[2-[(4aS,5aR)-5a-methyl-4,4a,5,6-tetrahydro-1H-cyclopropa[f]indazol-3-yl]-7-hydroxy-3H-benzimidazol-5-yl]-N-methyl-2-morpholin-4-ylpropanamide	1834415: Inhibition of IL-2 in CD3/CD28 activated human CD4+ve Th cells preincubated for 15 mins followed by addition of immuno-cult and measured after 24 hrs by HTRF assay	ic50	0.0820	uM
3-(3,4-dimethoxyphenyl)-5-(4-piperazin-1-ylphenyl)-1H-pyrrolo[2,3-b]pyridine	2068006: Activation of IL-2 in human Jurkat cells incubated for 24 hrs by ELISA	ec50	0.0904	uM
(2S)-N-[2-[(4aS,5aR)-5a-methyl-4,4a,5,6-tetrahydro-1H-cyclopropa[f]indazol-3-yl]-6-ethyl-1H-benzimidazol-5-yl]-N-methyl-2-morpholin-4-ylpropanamide	1834415: Inhibition of IL-2 in CD3/CD28 activated human CD4+ve Th cells preincubated for 15 mins followed by addition of immuno-cult and measured after 24 hrs by HTRF assay	ic50	0.0910	uM
N-[5-[5-(5,5-dimethyl-4-oxo-1,2-oxazol-3-yl)-2-methylphenyl]pyrazin-2-yl]-3,5-difluoropyridine-4-carboxamide	1774679: Inhibition of PHA-stimulated IL2 secretion in human Jurkat T cells preincubated for 10 mins followed by PHA addition and measured after 20 to 24 hrs by ELISA	ic50	0.0944	uM
N-[2-[(4aS,5aR)-5a-methyl-4,4a,5,6-tetrahydro-1H-cyclopropa[f]indazol-3-yl]-6-methyl-1H-benzimidazol-5-yl]-N-methyl-2-(3-oxomorpholin-4-yl)acetamide	1834415: Inhibition of IL-2 in CD3/CD28 activated human CD4+ve Th cells preincubated for 15 mins followed by addition of immuno-cult and measured after 24 hrs by HTRF assay	ic50	0.0960	uM
4-[4-[3-(3,4-dimethoxyphenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]phenyl]morpholine	2068006: Activation of IL-2 in human Jurkat cells incubated for 24 hrs by ELISA	ec50	0.0973	uM
3-(3,4-dimethoxyphenyl)-5-(6-piperazin-1-yl-3-pyridinyl)-1H-pyrrolo[2,3-b]pyridine	2068006: Activation of IL-2 in human Jurkat cells incubated for 24 hrs by ELISA	ec50	0.1084	uM
(2R)-N-[2-[(4aS,5aR)-5a-methyl-4,4a,5,6-tetrahydro-1H-cyclopropa[f]indazol-3-yl]-6-methyl-1H-benzimidazol-5-yl]-N-methyl-2-morpholin-4-ylpropanamide	1834415: Inhibition of IL-2 in CD3/CD28 activated human CD4+ve Th cells preincubated for 15 mins followed by addition of immuno-cult and measured after 24 hrs by HTRF assay	ic50	0.1130	uM
3-(4-methoxyphenyl)-7-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxychromen-4-one	1156797: Binding affinity to IL-2 (unknown origin)	kd	0.1200	uM
N-(2,6-difluorophenyl)-5-[5-(5,5-dimethyl-4-oxo-1,2-oxazol-3-yl)-2-methylphenyl]pyrazine-2-carboxamide	1774679: Inhibition of PHA-stimulated IL2 secretion in human Jurkat T cells preincubated for 10 mins followed by PHA addition and measured after 20 to 24 hrs by ELISA	ic50	0.1500	uM
2-chloro-N-[5-[5-(5,5-dimethyl-4-oxo-1,2-oxazol-3-yl)-2-methylphenyl]pyrazin-2-yl]benzamide	1774679: Inhibition of PHA-stimulated IL2 secretion in human Jurkat T cells preincubated for 10 mins followed by PHA addition and measured after 20 to 24 hrs by ELISA	ic50	0.1710	uM
N-[5-[5-(5,5-dimethyl-4-oxo-1,2-oxazol-3-yl)-2-methylphenyl]-2-pyridinyl]-2,6-difluorobenzamide	1774679: Inhibition of PHA-stimulated IL2 secretion in human Jurkat T cells preincubated for 10 mins followed by PHA addition and measured after 20 to 24 hrs by ELISA	ic50	0.1780	uM
(2R)-2-[(4-fluoro-1H-indole-2-carbonyl)amino]-3-(4-hydroxy-3-iodophenyl)propanoic acid	1774671: Binding affinity to L19-IL2 (unknown origin) by fluorescence polarization assay	kd	0.2100	uM
2,6-difluoro-N-[4-[2-methyl-5-(2-oxo-3H-1,3,4-oxadiazol-5-yl)phenyl]phenyl]benzamide	1774679: Inhibition of PHA-stimulated IL2 secretion in human Jurkat T cells preincubated for 10 mins followed by PHA addition and measured after 20 to 24 hrs by ELISA	ic50	0.2270	uM
N-[5-[5-(4-acetylpiperazine-1-carbonyl)-4-methoxy-2-methylphenyl]sulfanyl-1,3-thiazol-2-yl]-4-[(3,3-dimethylbutan-2-ylamino)methyl]benzamide	2029693: Inhibition of IL-2 in human Jurkat T cells pretreated with compound for 16 hrs followed by anti-CD3 stimulation by ELISA analysis	ec50	0.2376	uM
(2S)-2-[(4-fluoro-1H-indole-2-carbonyl)amino]-3-(3-iodophenyl)propanoic acid	1774671: Binding affinity to L19-IL2 (unknown origin) by fluorescence polarization assay	kd	0.2500	uM
(2S)-2-[(4-fluoro-1H-indole-2-carbonyl)amino]-3-(4-hydroxy-3-iodophenyl)propanoic acid	1774671: Binding affinity to L19-IL2 (unknown origin) by fluorescence polarization assay	kd	0.2500	uM
3-(3,4-dimethoxyphenyl)-5-[6-(4-methylpiperazin-1-yl)-3-pyridinyl]-1H-pyrrolo[2,3-b]pyridine	2068006: Activation of IL-2 in human Jurkat cells incubated for 24 hrs by ELISA	ec50	0.2750	uM
(2S)-2-[(6-fluoro-1H-indole-2-carbonyl)amino]-3-(4-hydroxy-3-iodophenyl)propanoic acid	1774671: Binding affinity to L19-IL2 (unknown origin) by fluorescence polarization assay	kd	0.2800	uM
(2S)-3-(3-bromo-4-hydroxyphenyl)-2-[(4-fluoro-1H-indole-2-carbonyl)amino]propanoic acid	1774671: Binding affinity to L19-IL2 (unknown origin) by fluorescence polarization assay	kd	0.3000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tetradecanoylphorbol Acetate	decreases expression, affects reaction, increases expression, increases phosphorylation, increases activity (+4 more)	31
Ionomycin	increases expression, increases secretion, affects reaction, increases activity, affects cotreatment (+3 more)	20
Lipopolysaccharides	affects secretion, affects cotreatment, increases expression, increases secretion, increases reaction (+1 more)	8
Dexamethasone	decreases secretion, affects cotreatment, decreases expression, decreases reaction, increases secretion (+4 more)	7
Tacrolimus	decreases expression, decreases reaction, increases expression, affects cotreatment	7
Particulate Matter	increases expression, decreases expression	6
Arsenic	affects cotreatment, increases expression, decreases expression, decreases secretion, increases abundance	5
Vehicle Emissions	affects cotreatment, decreases expression, increases expression	5
Plant Extracts	affects expression, decreases expression, decreases secretion, increases expression, increases secretion (+2 more)	5
Zinc	affects expression, affects cotreatment, affects reaction, increases expression, decreases expression	5
sodium arsenite	increases expression, decreases reaction, increases secretion, decreases expression, decreases secretion (+2 more)	4
Ribavirin	affects cotreatment, increases reaction, increases secretion, increases expression	4
Tretinoin	decreases activity, increases reaction, increases secretion, decreases expression, increases expression	4
Calcitriol	decreases reaction, increases phosphorylation, decreases expression, decreases secretion	3
Methotrexate	affects cotreatment, increases expression, affects reaction, decreases secretion	3
Cyclosporine	affects cotreatment, decreases expression, decreases reaction, increases expression	3
Sirolimus	affects cotreatment, decreases reaction, increases expression, increases phosphorylation, decreases response to substance	3
cobaltous chloride	affects cotreatment, decreases expression, decreases secretion	2
nickel chloride	affects cotreatment, increases secretion, decreases reaction, increases activity	2
cordycepin	decreases secretion	2
SB 203580	affects reaction, increases expression, affects cotreatment, decreases reaction, increases secretion	2
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases reaction, increases expression, increases activity, increases phosphorylation, affects cotreatment (+1 more)	2
Calcimycin	affects cotreatment, decreases reaction, increases expression, increases secretion	2
Resveratrol	affects cotreatment, decreases reaction, increases expression, decreases expression	2
Zoledronic Acid	affects expression, affects reaction, increases reaction	2
Alitretinoin	increases secretion, decreases expression, increases reaction	2
Acetylcysteine	decreases abundance, decreases expression, decreases reaction, increases phosphorylation, decreases activity	2
Chloroquine	affects cotreatment, decreases expression	2
Chlorpromazine	increases phosphorylation, affects cotreatment, decreases expression, decreases reaction	2
Coal	decreases expression, increases abundance	2

ChEMBL screening assays

35 unique, capped per target: 34 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3077408	Binding	Binding affinity to IL2 (unknown origin) assessed as inhibition of binding to IL2 receptor alpha	In vitro and in silico exploration of IL-2 inhibition by small drug-like molecules — *Med Chem Res*
CHEMBL5029737	ADMET	Induction of stability of human recombinant interleukin 2 assessed as area under curve in Sprague-Dawley rat at 0.8 mg/kg, iv measured up to 24 hrs by ELISA (Rvb= 251.22 +/- 11.60 ng.hr/ml)	Enhancing the Pharmacokinetic Profile of Interleukin 2 through Site-Specific Conjugation to a Selective Small-Molecule Transthyretin Ligand. — *J Med Chem*

Cellosaurus cell lines

24 cell lines: 24 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_3755	NK-92MI	Cancer cell line	Male
CVCL_6923	JEG-3/VP16-IL-2	Cancer cell line	Male
CVCL_A9JC	P815 Hsp65-IL-2	Cancer cell line	Male
CVCL_B3PC	TR-IL2-NK-92	Cancer cell line	Male
CVCL_B3PD	TR-IL2-YT	Cancer cell line	Male
CVCL_C3HM	RCC-26/CD80/IL-2	Cancer cell line
CVCL_E3G7	RenCa/IL2Hi	Cancer cell line	Male
CVCL_E3G8	RenCa/IL2Mo	Cancer cell line	Male
CVCL_E4CQ	NCI-H69/IL2	Cancer cell line	Male
CVCL_E4CR	NCI-H69/IL2/IFN-gamma	Cancer cell line	Male

Clinical trials (associated diseases)

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

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT00092183	Phase 4	COMPLETED	An Investigational Drug for the Prevention of Chemotherapy-Induced Nausea and Vomiting (MK-0869-071)
NCT00128778	Phase 4	COMPLETED	Maintenance Treatment With Liposomal Doxorubicin (Caelyx) in Metastatic Breast Cancer Patients
NCT00302120	Phase 4	UNKNOWN	The MONET - Study: MR Mammography of Nonpalpable Breast Tumors
NCT00307606	Phase 4	UNKNOWN	Does a Single Steroid Injection Reduce the Formation of Postmastectomy Seroma
NCT00370240	Phase 4	COMPLETED	Chlorhydrate of Ropivacaine and Breast Cancer Surgery
NCT00375752	Phase 4	TERMINATED	Efficacy and Safety of Letrozole vs. Letrozole Plus Zoledronic Acid as Endocrine Therapy Before Surgery in Postmenopausal Patients With Breast Cancer
NCT00575354	Phase 4	COMPLETED	Comparison of Sevoflurane and Isoflurane Anesthesia for Benign Breast Tumor Excision
NCT00604968	Phase 4	TERMINATED	Pegylated Liposomal Doxorubicin (Caelyx(R)) as Monotherapy in Elderly Patients With Locally Advanced and/or Metastatic Breast Cancer (Study P05059)
NCT00616135	Phase 4	COMPLETED	Study of Autologous Fat Enhanced w/ Regenerative Cells Transplanted to Reconstruct Breast Deformities After Lumpectomy
NCT00649090	Phase 4	COMPLETED	A Study to Evaluate the Safety of Adjuvant Treatment With Exemestane Following Previous Treatment With Tamoxifen in Postmenopausal Women With Estrogen Sensitive Primary Breast Cancer
NCT00779285	Phase 4	TERMINATED	Safety Study of CAELYX in Patients With Metastatic Breast Cancer Previously Treated With Anthracyclines (Study P04057)(TERMINATED)
NCT01176916	Phase 4	COMPLETED	Aromasin® Interventional Study Of Early Invasive Breast Cancer Patients In China
NCT01427400	Phase 4	UNKNOWN	The Use of Botulinum Toxin A in Two-Stage Tissue Expander/ Implant Breast Reconstruction
NCT01849380	Phase 4	UNKNOWN	Neoadjuvant ECS Versus ECF in Local Advanced Breast Cancer
NCT01859936	Phase 4	COMPLETED	Will Preoperative MRI Breast in Women Under 56 Years With Breast Cancer Change Primary Treatment
NCT01948960	Phase 4	COMPLETED	Influence of Exceptional Patient Characteristics on Everolimus Exposure
NCT01961544	Phase 4	COMPLETED	Eribulin Mesylate Phase IV Clinical Trial in Korean Patients With Metastatic or Locally Advanced Breast Cancer
NCT01975064	Phase 4	COMPLETED	Cancer and Anesthesia: Survival After Radical Surgery - a Comparison Between Propofol or Sevoflurane Anesthesia
NCT02004834	Phase 4	ACTIVE_NOT_RECRUITING	Levobupivacaine and Lidocaine for Paravertebral Block Causes Greater Hemodynamic Oscillations Than Levobupivacaine
NCT02372305	Phase 4	WITHDRAWN	Comparison of FlexHD and Alloderm Outcomes in Breast Reconstructive Surgery
NCT02479347	Phase 4	COMPLETED	Wound Infections in Breast Cancer Surgery After Preoperative Skin Preparation With Chlorhexidine vs. Povidone-iodine
NCT02549677	Phase 4	COMPLETED	Epirubicin Versus Docetaxel Plus Cyclophosphamide in Lymph Node Negative, ER-positive, Her2-negative Breast Cancer
NCT02612870	Phase 4	UNKNOWN	Sienna+® Injection Time Study 4 Arms
NCT02627560	Phase 4	COMPLETED	The Effect of Topical Tranexamic Acid on Bleeding and Seroma Formation in After Undergoing Mastectomy
NCT02661932	Phase 4	COMPLETED	Fertility Preservation in Breast Cancer Patients
NCT02781259	Phase 4	UNKNOWN	Selective Lymph Node Dissection Using Fluorescent Dye in Node-positive Breast Cancer
NCT02819921	Phase 4	TERMINATED	Desvenlafaxine for Treatment of Hot Flashes in Women With Breast Cancer Taking Tamoxifen
NCT03220178	Phase 4	TERMINATED	Impact of eHealth-support on Quality of Life in Metastatic Breast Cancer Patients Treated With Palbociclib and Endocrine Therapy
NCT03583944	Phase 4	COMPLETED	A Study to Evaluate Safety, Tolerability and Efficacy of Eribulin Mesylate in Treating Adult Females With Locally Advanced or Metastatic Breast Cancer
NCT03586154	Phase 4	COMPLETED	Combined Intra-articular Shoulder Injection and Stellate Ganglion Block in Chronic Post-mastectomy Shoulder Pain
NCT04707196	Phase 4	COMPLETED	A Study of Abemaciclib in Indian Women With Advanced Breast Cancer
NCT04931615	Phase 4	COMPLETED	ARTISS a Single-centre Randomised Control Study
NCT05033769	Phase 4	UNKNOWN	Assessing ImmunoResponse Post Eribulin: Eribulin and Immunogenicity in Advanced Breast Cancer
NCT05036005	Phase 4	UNKNOWN	Neoadjuvant Ontruzant (SB3) in Patients With HER2-positive Early Breast Cancer: An Open-Label (NeoON)
NCT05452213	Phase 4	RECRUITING	Comprehensive Analysis of Spatial, Temporal and Molecular Patterns of Ribociclib Efficacy and Resistance in Advanced Breast Cancer Patients
NCT05465031	Phase 4	RECRUITING	Sacubitril/Valsartan in PriMAry preventIoN of the Cardiotoxicity of Systematic breaST canceR trEAtMent (MAINSTREAM)
NCT05949333	Phase 4	UNKNOWN	Reducing Neutropenia Incidence With Pegfilgrastim Administration on Day 3 After Chemotherapy
NCT07158164	Phase 4	RECRUITING	DPYD Pharmacogenomics and Fluoropyrimidine (FP) Dose-Adjustment
NCT07162259	Phase 4	NOT_YET_RECRUITING	Cohort Study on Sequential ADC Therapy in HR-positive/HER2-negative Advanced Breast Cancer
NCT00000611	Phase 3	COMPLETED	Women’s Health Initiative (WHI)
NCT00001338	Phase 3	COMPLETED	A Prospective, Randomized, Phase III Trial of FLAC (5-Fluorouracil, Leucovorin, Adriamycin, Cytoxan) Chemotherapy With GM-CSF (Granulocyte-Macrophage Colony-Stimulating Factor) Versus PIXY 321 in Advanced Breast Cancer
NCT00021255	Phase 3	COMPLETED	Combination Chemotherapy With or Without Trastuzumab in Treating Women With Breast Cancer
NCT00034125	Phase 3	COMPLETED	Phase 3 Study of LY353381 Vs Tamoxifen in Women With Locally Advanced or Metastatic Breast Cancer.
NCT00036270	Phase 3	COMPLETED	Randomized Phase III Study Of Exemestane (Aromasin) For 5 Years Versus Tamoxifen for 2.5 to 3 Years Followed By Exemestane
NCT00038467	Phase 3	COMPLETED	Randomized Trial Of Exemestane Versus Continued Tamoxifen In Postmenopausal Women With Early Breast Cancer
NCT00039780	Phase 3	COMPLETED	Evaluation of BNP7787 for the Prevention of Neurotoxicity in Metastatic Breast Cancer Patients Receiving Weekly Paclitaxel
NCT00044291	Phase 3	COMPLETED	Phase III Study of Atamestane Plus Toremifene Versus Letrozole in Advanced Breast Cancer
NCT00046527	Phase 3	COMPLETED	Study of ABI-007 and Taxol in Patients With Metastatic Breast Cancer
NCT00050011	Phase 3	COMPLETED	Zoledronic Acid - Letrozole Adjuvant Synergy Trial (ZFAST) - Cancer Treatment Related Bone Loss in Postmenopausal Women With Estrogen Receptor Positive and/or Progesterone Receptor Positive Breast Cancer Receiving Adjuvant Hormonal Therapy
NCT00073528	Phase 3	COMPLETED	Study Comparing Lapatinib (GW572016) And Letrozole Versus Letrozole In Subjects With Advanced Or Metastatic Breast Cancer
NCT00083993	Phase 3	TERMINATED	Study Evaluating CCI-779 and Letrozole in Post-menopausal Women With Breast Cancer
NCT00092196	Phase 3	COMPLETED	Study of MK0869 for the Prevention of Chemotherapy-Induced Nausea and Vomiting (0869-071)(COMPLETED)
NCT00097344	Phase 3	TERMINATED	The CAT Study: Atamestane Plus Toremifene Versus Letrozole in Advanced Breast Cancer
NCT00115713	Phase 3	COMPLETED	Effects of Aerobic Exercise Versus Weight Training in Breast Cancer Survivors During Chemotherapy
NCT00121992	Phase 3	COMPLETED	Docetaxel, Doxorubicin (A), Cyclophosphamide (C) (TAC) vs 5-Fluorouracil, A, C (5FAC) Breast Cancer Adjuvant Treatment
NCT00138814	Phase 3	UNKNOWN	Boost Use in Breast Conservation Radiotherapy
NCT00143390	Phase 3	COMPLETED	Aromasin Vs Arimidex Study As Initial Hormonal Therapy In Postmenopausal Women With Advanced/Recurrent Breast Cancer
NCT00150917	Phase 3	COMPLETED	RCT of a Group Intervention for Women With a Family History of Breast Cancer
NCT00174655	Phase 3	COMPLETED	BIG 02/98 Docetaxel - Breast Cancer
NCT00174707	Phase 3	COMPLETED	Study of Docetaxel in Breast Cancer Patients

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for IL2 across ~30M SureChEMBL compounds — explore on Sugi Predict.