Target Information

Target General Information

Top

Target ID

T42000 (Former ID: TTDS00447)

Target Name

Interleukin-1 beta (IL1B)

Synonyms

IL1F2; IL-1beta; IL-1 beta; Catabolin

Gene Name

IL1B

Target Type

Successful target

[1]

Disease

[+] 4 Target-related Diseases

Mineral excesses [ICD-11: 5B91]

Monogenic autoinflammatory syndrome [ICD-11: 4A60]

Osteoarthritis [ICD-11: FA00-FA05]

Rheumatoid arthritis [ICD-11: FA20]

Function

Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, B-cell activation and antibody production, and fibroblast proliferation and collagen production. Promotes Th17 differentiation of T-cells. Synergizes with IL12/interleukin-12 to induce IFNG synthesis from T-helper 1 (Th1) cells. Potent proinflammatory cytokine.

Click to Show/Hide

BioChemical Class

Cytokine: interleukin

UniProt ID

IL1B_HUMAN

Sequence

MAEVPELASEMMAYYSGNEDDLFFEADGPKQMKCSFQDLDLCPLDGGIQLRISDHHYSKG
FRQAASVVVAMDKLRKMLVPCPQTFQENDLSTFFPFIFEEEPIFFDTWDNEAYVHDAPVR
SLNCTLRDSQQKSLVMSGPYELKALHLQGQDMEQQVVFSMSFVQGEESNDKIPVALGLKE
KNLYLSCVLKDDKPTLQLESVDPKNYPKKKMEKRFVFNKIEINNKLEFESAQFPNWYIST
SQAENMPVFLGGTKGGQDITDFTMQFVSS

Click to Show/Hide

3D Structure

Click to Show 3D Structure of This Target

AlphaFold

ADReCS ID

BADD_A03633 ; BADD_A04013 ; BADD_A05078

HIT2.0 ID

T64BTV

Drugs and Modes of Action

Top

Approved Drug(s)

[+] 4 Approved Drugs

Canakinumab

Drug Info

Approved

Rheumatoid arthritis

[2], [3]

Gallium nitrate

Drug Info

Approved

Hypercalcaemia

[4]

Glucosamine

Drug Info

Approved

Osteoarthritis

[5], [6]

Rilonacept

Drug Info

Approved

Arthritis

[7], [8]

Clinical Trial Drug(s)

[+] 6 Clinical Trial Drugs

XOMA 052

Drug Info

Phase 3

Type-2 diabetes

[9]

ABT-981

Drug Info

Phase 2

Osteoarthritis

[10], [11]

AC-201

Drug Info

Phase 2

Type-2 diabetes

[12]

LY-2189102

Drug Info

Phase 2

Cardiovascular disease

[13]

CYT-013-IL1bQb

Drug Info

Phase 1

Inflammation

[14]

TT-301

Drug Info

Phase 1

Alzheimer disease

[15]

Discontinued Drug(s)

[+] 1 Discontinued Drugs

CDP-484

Drug Info

Discontinued in Phase 1/2

Immune System disease

[16]

Preclinical Drug(s)

[+] 1 Preclinical Drugs

Celastrol

Drug Info

Preclinical

Motor neurone disease

[17]

Mode of Action

[+] 3 Modes of Action

Inhibitor

[+] 6 Inhibitor drugs

Gallium nitrate

Drug Info

[1]

Glucosamine

Drug Info

[19]

Diacerein

Drug Info

[20]

AC-201

Drug Info

[12]

TT-301

Drug Info

[25]

CDP-484

Drug Info

[26]

Modulator

[+] 3 Modulator drugs

Rilonacept

Drug Info

[8]

ABT-981

Drug Info

[22]

DVD-Ig

Drug Info

[24]

Suppressor

[+] 1 Suppressor drugs

Celastrol

Drug Info

[17]

Chemical Structure based Activity Landscape of Target

Top

Drug Property Profile of Target

Top

(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

Co-Targets

Top

Co-Targets

Co-Targets Info

Target Regulators

Top

Target-regulating microRNAs

Target-regulating microRNAs Info

Target-regulating Transcription Factors

Target-regulating Transcription Factors Info

Target Profiles in Patients

Top

Target Expression
Profile (TEP)

Target Expression Profile Info

Target Affiliated Biological Pathways		Top
KEGG Pathway	[+] 30 KEGG Pathways	+
1	MAPK signaling pathway
2	Cytokine-cytokine receptor interaction
3	NF-kappa B signaling pathway
4	Apoptosis
5	Osteoclast differentiation
6	Toll-like receptor signaling pathway
7	NOD-like receptor signaling pathway
8	Cytosolic DNA-sensing pathway
9	Hematopoietic cell lineage
10	TNF signaling pathway
11	Inflammatory mediator regulation of TRP channels
12	Non-alcoholic fatty liver disease (NAFLD)
13	Type I diabetes mellitus
14	Alzheimer's disease
15	Prion diseases
16	Salmonella infection
17	Pertussis
18	Legionellosis
19	Leishmaniasis
20	Chagas disease (American trypanosomiasis)
21	African trypanosomiasis
22	Malaria
23	Amoebiasis
24	Tuberculosis
25	Measles
26	Influenza A
27	Herpes simplex infection
28	Inflammatory bowel disease (IBD)
29	Rheumatoid arthritis
30	Graft-versus-host disease
NetPath Pathway	[+] 9 NetPath Pathways	+
1	Leptin Signaling Pathway
2	IL5 Signaling Pathway
3	IL1 Signaling Pathway
4	IL2 Signaling Pathway
5	IL3 Signaling Pathway
6	TGF_beta_Receptor Signaling Pathway
7	Wnt Signaling Pathway
8	TCR Signaling Pathway
9	TNFalpha Signaling Pathway
PID Pathway	[+] 6 PID Pathways	+
1	IL27-mediated signaling events
2	IL12-mediated signaling events
3	IL1-mediated signaling events
4	IFN-gamma pathway
5	IL23-mediated signaling events
6	Cellular roles of Anthrax toxin
Reactome	[+] 3 Reactome Pathways	+
1	Interleukin-1 signaling
2	Interleukin-1 processing
3	CLEC7A/inflammasome pathway
WikiPathways	[+] 24 WikiPathways	+
1	Toll-like receptor signaling pathway
2	Monoamine Transport
3	SIDS Susceptibility Pathways
4	TCR Signaling Pathway
5	Type II interferon signaling (IFNG)
6	Senescence and Autophagy in Cancer
7	Cytokines and Inflammatory Response
8	MAPK Signaling Pathway
9	Myometrial Relaxation and Contraction Pathways
10	Aryl Hydrocarbon Receptor Pathway
11	IL1 and megakaryotyces in obesity
12	Hematopoietic Stem Cell Differentiation
13	Spinal Cord Injury
14	Allograft Rejection
15	Alzheimers Disease
16	Leptin signaling pathway
17	IL-1 signaling pathway
18	Interleukin-1 signaling
19	Folate Metabolism
20	Vitamin B12 Metabolism
21	Selenium Micronutrient Network
22	Serotonin Transporter Activity
23	Regulation of toll-like receptor signaling pathway
24	NOD pathway

Target-Related Models and Studies

Top

Target Validation

Target Validation Info

References

Top

REF 1

Elimination of arthritis pain and inflammation for over 2 years with a single 90 min, topical 14% gallium nitrate treatment: case reports and revie... Med Hypotheses. 2005;65(6):1136-41.

REF 2

URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6773).

REF 3

Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.

REF 4

Drug information of Gallium nitrate, 2008. eduDrugs.

REF 5

REF 6

Drug information of Glucosamine, 2008. eduDrugs.

REF 7

REF 8

2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.

REF 9

ClinicalTrials.gov (NCT02258867) Efficacy and Safety Study of Gevokizumab to Treat Behcet's Disease Uveitis. U.S. National Institutes of Health.

REF 10

ClinicalTrials.gov (NCT02087904) A Phase 2a Study Evaluating the Safety, Efficacy, and Pharmacodynamic Effects of ABT-981 in Patients With Knee Osteoarthritis

REF 11

ClinicalTrials.gov (NCT02384538) A Phase 2a Study Evaluating the Safety and Efficacy of ABT-981 in Patients With Erosive Hand Osteoarthritis

REF 12

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

REF 13

ClinicalTrials.gov (NCT00942188) A Study of LY2189102 in Patients With Type 2 Diabetes. U.S. National Institutes of Health.

REF 14

ClinicalTrials.gov (NCT00924105) Safety, Tolerability and Pharmacodynamics of CYT013-IL1bQb in Patients With Type 2 Diabetes. U.S. National Institutes of Health.

REF 15

ClinicalTrials.gov (NCT01357421) Effects of TT301 on Cytokine Levels Post Endotoxin Challenge. U.S. National Institutes of Health.

REF 16

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800016757)

REF 17

Emerging disease-modifying therapies for the treatment of motor neuron disease/amyotropic lateral sclerosis. Expert Opin Emerg Drugs. 2007 May;12(2):229-52.

REF 18

Emerging drugs for rheumatoid arthritis. Expert Opin Emerg Drugs. 2008 Mar;13(1):175-96.

REF 19

Glucosamine inhibits IL-1beta-mediated IL-8 production in prostate cancer cells by MAPK attenuation. J Cell Biochem. 2009 Oct 1;108(2):489-98.

REF 20

Non-surgical treatment of osteoarthritis of large joints - new aspects. Wien Med Wochenschr. 2009;159(3-4):76-86.

REF 21

Gevokizumab, an anti-IL-1beta mAb for the potential treatment of type 1 and 2 diabetes, rheumatoid arthritis and cardiovascular disease. Curr Opin Mol Ther. 2010 Dec;12(6):755-69.

REF 22

Generation and characterization of ABT-981, a dual variable domain immunoglobulin (DVD-Ig(TM)) molecule that specifically and potently neutralizes both IL-1alpha and IL-1beta. MAbs. 2015;7(3):605-19.

REF 23

Double-blind, randomized study evaluating the glycemic and anti-inflammatory effects of subcutaneous LY2189102, a neutralizing IL-1beta antibody, in patients with type 2 diabetes. Diabetes Care. 2013Aug;36(8):2239-46.

REF 24

REF 25

A Swell in the Armamentarium of Antiepileptic Drug Targets. Epilepsy Curr. 2011 Nov-Dec; 11(6): 172-176.

REF 26

Biological targets for therapeutic interventions in COPD: clinical potential. Int J Chron Obstruct Pulmon Dis. 2006 September; 1(3): 321-334.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.

Prof. Yuzong CHEN

Prof. Feng ZHU