Target Information

Target General Information

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Target ID

T61698 (Former ID: TTDR00141)

Target Name

Interleukin-2 (IL2)

Synonyms

TCGF; T-cell growth factor; IL-2; Aldesleukin

Gene Name

IL2

Target Type

Successful target

[1]

Disease

[+] 2 Target-related Diseases

Multiple sclerosis [ICD-11: 8A40]

Renal cell carcinoma [ICD-11: 2C90]

Function

Produced by T-cells in response to antigenic or mitogenic stimulation, this protein is required for T-cell proliferation and other activities crucial to regulation of the immune response. Can stimulate B-cells, monocytes, lymphokine-activated killer cells, natural killer cells, and glioma cells.

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BioChemical Class

Cytokine: interleukin

UniProt ID

IL2_HUMAN

Sequence

MYRMQLLSCIALSLALVTNSAPTSSSTKKTQLQLEHLLLDLQMILNGINNYKNPKLTRML
TFKFYMPKKATELKHLQCLEEELKPLEEVLNLAQSKNFHLRPRDLISNINVIVLELKGSE
TTFMCEYADETATIVEFLNRWITFCQSIISTLT

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3D Structure

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PDB

ADReCS ID

BADD_A03025

HIT2.0 ID

T34DZ7

Drugs and Modes of Action

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Approved Drug(s)

[+] 2 Approved Drugs

Aldesleukin

Drug Info

Approved

Renal cell carcinoma

[2]

Daclizumab

Drug Info

Approved

Multiple sclerosis

[3]

Clinical Trial Drug(s)

[+] 16 Clinical Trial Drugs

AIR-insulin

Drug Info

Phase 3

Diabetic complication

[4]

TG-4010

Drug Info

Phase 2/3

Bipolar disorder

[5]

APN-301

Drug Info

Phase 2

Melanoma

[6]

BNZ-1

Drug Info

Phase 2

Cutaneous T-cell lymphoma

[7]

Carboxyamidotriazole orotate

Drug Info

Phase 2

Glioblastoma multiforme

[8]

Human interleukin-2

Drug Info

Phase 2

Renal cell carcinoma

[9]

IL-2/CD40L-expressing leukemia vaccine

Drug Info

Phase 2

Chronic lymphocytic leukaemia

[10]

L19-IL-2 fusion protein

Drug Info

Phase 2

Lymphoma

[11]

Leuvectin

Drug Info

Phase 2

Melanoma

[12]

Thymoctonan

Drug Info

Phase 2

Immune System disease

[13]

IL-2 XL

Drug Info

Phase 1/2

Renal cell carcinoma

[14]

IL-2/gene-modified lymphocytes

Drug Info

Phase 1/2

Ovarian cancer

[15]

Medusa IL-2

Drug Info

Phase 1/2

Solid tumour/cancer

[16]

ASP9801

Drug Info

Phase 1

Solid tumour/cancer

[17]

SAR444245

Drug Info

Phase 1

Solid tumour/cancer

[18]

VCL-1M01

Drug Info

Phase 1

Melanoma

[19]

Discontinued Drug(s)

[+] 6 Discontinued Drugs

Nuleusin

Drug Info

Discontinued in Phase 3

Melanoma

[20]

PMI-001

Drug Info

Discontinued in Phase 3

Lupus

[21]

BIWB-1

Drug Info

Discontinued in Phase 2

Melanoma

[22]

VLTS-587

Drug Info

Discontinued in Phase 2

Lung cancer

[23]

Roquinimex

Drug Info

Discontinued in Phase 1

Rheumatoid arthritis

[24]

TG-1024

Drug Info

Discontinued in Phase 1

Solid tumour/cancer

[25]

Preclinical Drug(s)

[+] 1 Preclinical Drugs

VPM-4-001

Drug Info

Preclinical

Prostate cancer

[26]

Mode of Action

[+] 3 Modes of Action

Modulator

[+] 19 Modulator drugs

Aldesleukin

Drug Info

[1]

Daclizumab

Drug Info

[3]

AIR-insulin

Drug Info

[27]

TG-4010

Drug Info

[5]

APN-301

Drug Info

[28]

Human interleukin-2

Drug Info

[31]

Leuvectin

Drug Info

[34]

Thymoctonan

Drug Info

[35]

IL-2 XL

Drug Info

[16]

IL-2/gene-modified lymphocytes

Drug Info

[36]

Medusa IL-2

Drug Info

[37]

VCL-1M01

Drug Info

[40]

VLTS-587

Drug Info

[44]

Roquinimex

Drug Info

[45]

TG-1024

Drug Info

[46]

IL-2 antibody (anti-tumor)

Drug Info

[48]

interleukin-2, Roussel Uclaf

Drug Info

[49]

TG-1031

Drug Info

[51]

TG-2001

Drug Info

[52]

Inhibitor

[+] 5 Inhibitor drugs

BNZ-1

Drug Info

[29]

Carboxyamidotriazole orotate

Drug Info

[30]

PMI-001

Drug Info

[42]

SP2456

Drug Info

[50]

SP4160

Drug Info

[50]

Agonist

[+] 1 Agonist drugs

Nuleusin

Drug Info

[41]

Drug Property Profile of Target

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(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five

Target Regulators

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Target-regulating microRNAs

Target-regulating microRNAs Info

Target-regulating Transcription Factors

Target-regulating Transcription Factors Info

Target Profiles in Patients

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Target Expression
Profile (TEP)

Target Expression Profile Info

Target Affiliated Biological Pathways		Top
KEGG Pathway	[+] 13 KEGG Pathways	+
1	Cytokine-cytokine receptor interaction
2	PI3K-Akt signaling pathway
3	Jak-STAT signaling pathway
4	T cell receptor signaling pathway
5	Intestinal immune network for IgA production
6	Type I diabetes mellitus
7	Chagas disease (American trypanosomiasis)
8	Measles
9	HTLV-I infection
10	Autoimmune thyroid disease
11	Inflammatory bowel disease (IBD)
12	Allograft rejection
13	Graft-versus-host disease
NetPath Pathway	[+] 3 NetPath Pathways	+
1	IL-7 Signaling Pathway
2	TCR Signaling Pathway
3	TNFalpha Signaling Pathway
Panther Pathway	[+] 2 Panther Pathways	+
1	Inflammation mediated by chemokine and cytokine signaling pathway
2	Interleukin signaling pathway
PID Pathway	[+] 15 PID Pathways	+
1	IL27-mediated signaling events
2	IL12-mediated signaling events
3	Calcineurin-regulated NFAT-dependent transcription in lymphocytes
4	SHP2 signaling
5	Regulation of Telomerase
6	Glucocorticoid receptor regulatory network
7	IL2-mediated signaling events
8	IL2 signaling events mediated by PI3K
9	AP-1 transcription factor network
10	IL23-mediated signaling events
11	IL2 signaling events mediated by STAT5
12	Calcium signaling in the CD4+ TCR pathway
13	Downstream signaling in na&#xef
14
15	IL12 signaling mediated by STAT4
Reactome	[+] 5 Reactome Pathways	+
1	GPVI-mediated activation cascade
2	G beta:gamma signalling through PI3Kgamma
3	Interleukin-2 signaling
4	RAF/MAP kinase cascade
5	Interleukin receptor SHC signaling
WikiPathways	[+] 13 WikiPathways	+
1	Cytokines and Inflammatory Response
2	IL-2 Signaling Pathway
3	Inflammatory Response Pathway
4	Aryl Hydrocarbon Receptor Pathway
5	Interleukin-2 signaling
6	T-Cell Receptor and Co-stimulatory Signaling
7	Spinal Cord Injury
8	Corticotropin-releasing hormone
9	Allograft Rejection
10	Arylhydrocarbon receptor (AhR) signaling pathway
11	Interleukin-3, 5 and GM-CSF signaling
12	Folate Metabolism
13	IL-5 Signaling Pathway

References

Top

REF 1

Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.

REF 2

Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.

REF 3

2016 FDA drug approvals. Nat Rev Drug Discov. 2017 Feb 2;16(2):73-76.

REF 4

Clinical pipeline report, company report or official report of Eli Lilly.

REF 5

A phase II study of Tg4010 (Mva-Muc1-Il2) in association with chemotherapy in patients with stage III/IV Non-small cell lung cancer. J Thorac Oncol. 2008 Jul;3(7):735-44.

REF 6

ClinicalTrials.gov (NCT00590824) Pilot hu14.18-IL2 in Resectable Recurrent Stage III or Stage IV Melanoma. U.S. National Institutes of Health.

REF 7

Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)

REF 8

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800032169)

REF 9

Clinical pipeline report, company report or official report of Immunservice GmbH.

REF 10

ClinicalTrials.gov (NCT01604031) Treatment of B-CLL With Autologous IL2 and CD40 Ligand-Expressing Tumor Cells + Lenalidomide. U.S. National Institutes of Health.

REF 11

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800026492)

REF 12

ClinicalTrials.gov (NCT00004050) Leuvectin Followed By Surgery in Treating Patients With Stage II or Stage III Prostate Cancer. U.S. National Institutes of Health.

REF 13

ClinicalTrials.gov (NCT00002435) A Study of Thymic Humoral Factor (THF Gamma 2) in HIV-Infected Patients. U.S. National Institutes of Health.

REF 14

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800020218)

REF 15

ClinicalTrials.gov (NCT00062036) Cyclophosphamide and Fludarabine Followed By Interleukin-2 Gene-Modified Tumor Infiltrating Lymphocytes in Treating Patients With Metastatic Melanoma. U.S. National Institutes of Health.

REF 16

Pharmacokinetics (PK) and immunologic responses in a phase I/II study of a sustained release formulation of IL-2 in renal cell carcinoma (RCC) patients. J Clin Oncol (Meeting Abstracts) June 2006 vol. 24 no. 18_suppl 2558.

REF 17

ClinicalTrials.gov (NCT03954067) A Study of an Intratumoral Oncolytic Virus in Patients With Advanced Metastatic Solid Tumors. U.S. National Institutes of Health.

REF 18

ClinicalTrials.gov (NCT04009681) A Study Evaluating Safety and Therapeutic Activity of THOR-707 in Adult Subjects With Advanced or Metastatic Solid Tumors (THOR-707-101). U.S. National Institutes of Health.

REF 19

ClinicalTrials.gov (NCT00223899) A Trial to Evaluate the Safety of Intratumoral VCL-IM01 Followed by Electroporation in Metastatic Melanoma. U.S. National Institutes of Health.

REF 20

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800027551)

REF 21

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800019789)

REF 22

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004906)

REF 23

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008879)

REF 24

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001478)

REF 25

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800009282)

REF 26

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800023655)

REF 27

The AIR inhaled insulin system: system components and pharmacokinetic/glucodynamic data. Diabetes Technol Ther. 2007 Jun;9 Suppl 1:S41-7.

REF 28

Clinical pipeline report, company report or official report of APEIRON Biologics.

REF 29

Clinical pipeline report, company report or official report of Bioniz Therapeutics.

REF 30

J Clin Oncol 32:5s, 2014 (suppl; abstr 2071).

REF 31

Clinical pipeline report, company report or official report of Immunservice.

REF 32

Immunotherapy of high-risk acute leukemia with a recipient (autologous) vaccine expressing transgenic human CD40L and IL-2 after chemotherapy and a... Blood. 2006 Feb 15;107(4):1332-41.

REF 33

National Cancer Institute Drug Dictionary (drug id 665656).

REF 34

Intratumoral interleukin 2 for renal-cell carcinoma by direct gene transfer of a plasmid DNA/DMRIE/DOPE lipid complex. World J Urol. 2000 Apr;18(2):152-6.

REF 35

Evaluation of efficacy and safety of thymus humoral factor-gamma 2 in the management of chronic hepatitis B. J Hepatol. 1995 Jul;23(1):21-7.

REF 36

Genetic modification of human T lymphocytes for the treatment of hematologic malignancies. Haematologica. 2012 November; 97(11): 1622-1631.

REF 37

Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.

REF 38

Clinical pipeline report, company report or official report of Astellas Pharma.

REF 39

Clinical pipeline report, company report or official report of Sanofi.

REF 40

Interleukin-2 gene therapy in a patient with glioblastoma. Gene Ther. 1995 Mar;2(2):164-7.

REF 41

Expression, purification and characterization of recombinant human interleukin-2-serum albumin (rhIL-2-HSA) fusion protein in Pichia pastoris. Protein Expr Purif. 2012 Jul;84(1):154-60.

REF 42

Development of a botanical anti-arthritis drug, PMI-001. SBIR.STTR America's Seed Fund.

REF 43

WO patent application no. 2013,1850,32, Nanotherapeutics for drug targeting.

REF 44

CN patent application no. 101039956, Cell surface glycoprotein.

REF 45

The novel immunomodulator, Linomide, stimulates interleukin-2-induced human natural killer (NK) cell and PHA-stimulated T cell proliferation from normal donors. Leuk Res. 1996 Jan;20(1):57-63.

REF 46

Melanoma and Immunotherapy. Hematology/Oncology Clinics of North America Volume 23, Issue 3, June 2009, Pages 547-564.

REF 47

BioPartnering North America--Programs from Pharma in Europe and the Middle East. IDrugs. 2010 Mar;13(3):162-5.

REF 48

An anti-IL-2 antibody increases serum half-life and improves anti-tumor efficacy of human recombinant interleukin-2. Immunopharmacology. 1994 Nov-Dec;28(3):223-32.

REF 49

Randomized study of recombinant interleukin-2 after autologous bone marrow transplantation for acute leukemia in first complete remission. Eur Cytokine Netw. 2000 Mar;11(1):91-8.

REF 50

How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.

REF 51

Technology evaluation: TG-1031, Transgene SA.Curr Opin Mol Ther.2000 Feb;2(1):106-11.

REF 52

Immunotherapy of metastatic melanoma by intratumoral injections of Vero cells producing human IL-2: phase II randomized study comparing two dose le... Cancer Gene Ther. 2002 Mar;9(3):289-95.

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