Target Information

Target General Infomation
Target ID
T03346
Former ID
TTDC00081
Target Name
Interleukin-4 receptor alpha chain
Gene Name
IL4R
Synonyms
CD124 antigen; IL-4R; IL-4R-alpha; IL4R
Target Type
Successful
Disease Asthma [ICD10: J45]
Asthma; Atopic dermatitis [ICD9: 493, 691.8, 692.9; ICD10: J45, L20-L30]
Cancer [ICD9: 140-229; ICD10: C00-C96]
Moderate-to-severe atopic dermatitis [ICD10: L20]
Pulmonary fibrosis [ICD9: 515, 516.3; ICD10: J84.1]
Function
This is a receptor for interleukin 4. A soluble form of the il4 receptor may represent a regulatory molecule specific for il4-dependent immune responses.
BioChemical Class
Cytokine receptor
Target Validation
T03346
UniProt ID
P24394
Sequence
MGWLCSGLLFPVSCLVLLQVASSGNMKVLQEPTCVSDYMSISTCEWKMNGPTNCSTELRL
LYQLVFLLSEAHTCIPENNGGAGCVCHLLMDDVVSADNYTLDLWAGQQLLWKGSFKPSEH
VKPRAPGNLTVHTNVSDTLLLTWSNPYPPDNYLYNHLTYAVNIWSENDPADFRIYNVTYL
EPSLRIAASTLKSGISYRARVRAWAQCYNTTWSEWSPSTKWHNSYREPFEQHLLLGVSVS
CIVILAVCLLCYVSITKIKKEWWDQIPNPARSRLVAIIIQDAQGSQWEKRSRGQEPAKCP
HWKNCLTKLLPCFLEHNMKRDEDPHKAAKEMPFQGSGKSAWCPVEISKTVLWPESISVVR
CVELFEAPVECEEEEEVEEEKGSFCASPESSRDDFQEGREGIVARLTESLFLDLLGEENG
GFCQQDMGESCLLPPSGSTSAHMPWDEFPSAGPKEAPPWGKEQPLHLEPSPPASPTQSPD
NLTCTETPLVIAGNPAYRSFSNSLSQSPCPRELGPDPLLARHLEEVEPEMPCVPQLSEPT
TVPQPEPETWEQILRRNVLQHGAAAAPVSAPTSGYQEFVHAVEQGGTQASAVVGLGPPGE
AGYKAFSSLLASSAVSPEKCGFGASSGEEGYKPFQDLIPGCPGDPAPVPVPLFTFGLDRE
PPRSPQSSHLPSSSPEHLGLEPGEKVEDMPKPPLPQEQATDPLVDSLGSGIVYSALTCHL
CGHLKQCHGQEDGGQTPVMASPCCGCCCGDRSSPPTTPLRAPDPSPGGVPLEASLCPASL
APSGISEKSKSSSSFHPAPGNAQSSSQTPKIVNFVSVGPTYMRVS
Drugs and Mode of Action
Drug(s) Dupilumab Drug Info Approved Moderate-to-severe atopic dermatitis [889446]
Dupilumab Drug Info Phase 3 Asthma [524442], [542567]
SAR231893 Drug Info Phase 3 Asthma; Atopic dermatitis [524747]
Aerovant Drug Info Phase 2a Asthma [536958]
Altrakincept Drug Info Phase 2 Asthma [889438]
PRX-321 Drug Info Phase 2 Cancer [522499]
SAR-156597 Drug Info Phase 2 Pulmonary fibrosis [549242]
AMG 317 Drug Info Discontinued in Phase 1 Asthma [547559]
Antagonist Aerovant Drug Info [551430]
AMG 317 Drug Info [550250], [551086]
APG-201 Drug Info [543460]
Modulator Altrakincept Drug Info [889443]
SAR231893 Drug Info [524972], [532365]
Inhibitor PRS-060 Drug Info [543460]
Agonist PRX-321 Drug Info [537389]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Cytokine-cytokine receptor interaction
PI3K-Akt signaling pathway
Jak-STAT signaling pathway
Hematopoietic cell lineage
Inflammatory bowel disease (IBD)
NetPath Pathway IL2 Signaling Pathway
IL4 Signaling Pathway
EGFR1 Signaling Pathway
PANTHER Pathway Interleukin signaling pathway
Pathway Interaction Database p73 transcription factor network
IL4-mediated signaling events
WikiPathways Inflammatory Response Pathway
IL-4 Signaling Pathway
References
Ref 522499ClinicalTrials.gov (NCT00797940) Convection Enhanced Localized Administration of PRX321 With Real-time Imaging for Therapy of Recurrent Glioblastoma (CLARITY-1). U.S. National Institutes of Health.
Ref 524442ClinicalTrials.gov (NCT01949311) Open-label Study of Dupilumab (REGN668/SAR231893) in Patients With Atopic Dermatitis. U.S. National Institutes of Health.
Ref 524747ClinicalTrials.gov (NCT02134028) Long-Term Safety Evaluation of Dupilumab in Patients With Asthma. U.S. National Institutes of Health.
Ref 536958Emerging drugs for asthma. Expert Opin Emerg Drugs. 2008 Dec;13(4):643-53.
Ref 542567(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: 7574).
Ref 547559Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800017312)
Ref 549242Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800034106)
Ref 889438Interleukin-4 receptor in moderate atopic asthma. A phase I/II randomized, placebo-controlled trial. Am J Respir Crit Care Med. 1999 Dec;160(6):1816-23.
Ref 889446Drugs@FDA (Edaravone)
Ref 524972ClinicalTrials.gov (NCT02277769) Study of Dupilumab (REGN668/SAR231893) Monotherapy Administered to Adult Patients With Moderate-to-Severe Atopic Dermatitis. U.S. National Institutes of Health.
Ref 532365Dupilumab in persistent asthma with elevated eosinophil levels. N Engl J Med. 2013 Jun 27;368(26):2455-66.
Ref 537389Convection-enhanced drug delivery of interleukin-4 pseudomonas exotoxin (PRX321): increased distribution and magnetic resonance monitoring. J Pharmacol Exp Ther. 2009 Aug;330(2):520-5. Epub 2009 May28.
Ref 543460(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. (Target id: 1697).
Ref 550250Clinical pipeline report, company report or official report of Amgen (2009).
Ref 551086Randomized, double-blind, placebo-controlled trial of the oral interleukin-12/23 inhibitor apilimod mesylate for treatment of active Crohn's disease. Inflamm Bowel Dis. 2010 Jul;16(7):1209-18.
Ref 551430Aerovance starts trial of Aerovant for uncontrolled asthma. Aerovance. March 3, 2009.
Ref 889443The potential of biologics for the treatment of asthma. Nat Rev Drug Discov. 2012 Dec;11(12):958-72. doi: 10.1038/nrd3792.

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