Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTDWHC3)

• DTT Name: Interleukin 4 receptor alpha (IL4R)
• Synonyms: Interleukin-4 receptor subunit alpha; IL4RA; IL-4RA; IL-4R-alpha; IL-4R subunit alpha; IL-4 receptor subunit alpha; CD124 antigen; CD124; 582J2.1
• Gene Name: IL4R
• DTT Type: Successful target; [1]
• BioChemical Class: Cytokine receptor
• UniProt ID: IL4RA_HUMAN
• TTD ID: T03346
• Sequence:
  MGWLCSGLLFPVSCLVLLQVASSGNMKVLQEPTCVSDYMSISTCEWKMNGPTNCSTELRL
  LYQLVFLLSEAHTCIPENNGGAGCVCHLLMDDVVSADNYTLDLWAGQQLLWKGSFKPSEH
  VKPRAPGNLTVHTNVSDTLLLTWSNPYPPDNYLYNHLTYAVNIWSENDPADFRIYNVTYL
  EPSLRIAASTLKSGISYRARVRAWAQCYNTTWSEWSPSTKWHNSYREPFEQHLLLGVSVS
  CIVILAVCLLCYVSITKIKKEWWDQIPNPARSRLVAIIIQDAQGSQWEKRSRGQEPAKCP
  HWKNCLTKLLPCFLEHNMKRDEDPHKAAKEMPFQGSGKSAWCPVEISKTVLWPESISVVR
  CVELFEAPVECEEEEEVEEEKGSFCASPESSRDDFQEGREGIVARLTESLFLDLLGEENG
  GFCQQDMGESCLLPPSGSTSAHMPWDEFPSAGPKEAPPWGKEQPLHLEPSPPASPTQSPD
  NLTCTETPLVIAGNPAYRSFSNSLSQSPCPRELGPDPLLARHLEEVEPEMPCVPQLSEPT
  TVPQPEPETWEQILRRNVLQHGAAAAPVSAPTSGYQEFVHAVEQGGTQASAVVGLGPPGE
  AGYKAFSSLLASSAVSPEKCGFGASSGEEGYKPFQDLIPGCPGDPAPVPVPLFTFGLDRE
  PPRSPQSSHLPSSSPEHLGLEPGEKVEDMPKPPLPQEQATDPLVDSLGSGIVYSALTCHL
  CGHLKQCHGQEDGGQTPVMASPCCGCCCGDRSSPPTTPLRAPDPSPGGVPLEASLCPASL
  APSGISEKSKSSSSFHPAPGNAQSSSQTPKIVNFVSVGPTYMRVS
• Function: Couples to the JAK1/2/3-STAT6 pathway. The IL4 response is involved in promoting Th2 differentiation. The IL4/IL13 responses are involved in regulating IgE production and, chemokine and mucus production at sites of allergic inflammation. In certain cell types, can signal through activation of insulin receptor substrates, IRS1/IRS2. Receptor for both interleukin 4 and interleukin 13.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  PI3K-Akt signaling pathway (hsa04151)
  Jak-STAT signaling pathway (hsa04630)
  Hematopoietic cell lineage (hsa04640)
  Inflammatory bowel disease (IBD) (hsa05321)
• Reactome Pathway: Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dupilumab	DMOAD2Y	Atopic dermatitis	EA80	Approved	[1]

7 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CBP-201	DMWYNN1	Atopic dermatitis	EA80	Phase 3	[2]
SAR231893	DMHFBOG	Asthma	CA23	Phase 3	[1]
Aerovant	DMUB8WN	Asthma	CA23	Phase 2a	[3]
Altrakincept	DMLSK01	Asthma	CA23	Phase 2	[4]
AZD1402	DM73O6I	Asthma	CA23	Phase 2	[5]
PRX-321	DM7YWVT	Solid tumour/cancer	2A00-2F9Z	Phase 2	[6]
SAR-156597	DMUICJD	Idiopathic pulmonary fibrosis	CB03.4	Phase 2	[7]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AMG 317	DMUO3T2	Asthma	CA23	Discontinued in Phase 1	[8]

2 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
APG-201	DM0BVJN	Solid tumour/cancer	2A00-2F9Z	Investigative	[7]
PRS-060	DM8GCHX	Asthma	CA23	Investigative	[7]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Asthma	CA23	Nasal and bronchial airway	1.02E-01	0.16	0.37
Idiopathic pulmonary fibrosis	CA23	Lung tissue	6.07E-02	-0.59	-1.29
Atopic dermatitis	EA90	Skin	1.48E-08	0.76	3.74

References

• [1] Dupilumab in persistent asthma with elevated eosinophil levels. N Engl J Med. 2013 Jun 27;368(26):2455-66.
• [2] Preclinical immunological characterization of rademikibart (CBP-201), a next-generation human monoclonal antibody targeting IL-4Ralpha, for the treatment of Th2 inflammatory diseases. Sci Rep. 2023 Jul 31;13(1):12411.
• [3] Aerovance starts trial of Aerovant for uncontrolled asthma. Aerovance. March 3, 2009.
• [4] The potential of biologics for the treatment of asthma. Nat Rev Drug Discov. 2012 Dec;11(12):958-72.
• [5] Elarekibep (PRS-060/AZD1402), a new class of inhaled Anticalin medicine targeting IL-4Ra for type 2 endotype asthma. J Allergy Clin Immunol. 2023 Apr;151(4):966-975.
• [6] Convection-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.
• [7] 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. (Target id: 1697).
• [8] Clinical pipeline report, company report or official report of Amgen (2009).