Details of the Drug Therapeutic Target (DTT)

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

• DTT Name: Interleukin-4 (IL4)
• Synonyms: Pitrakinra; Lymphocyte stimulatory factor 1; IL-4; Binetrakin; BSF-1; B-cell stimulatory factor 1
• Gene Name: IL4
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Cytokine: interleukin
• UniProt ID: IL4_HUMAN
• TTD ID: T00239
• Sequence:
  MGLTSQLLPPLFFLLACAGNFVHGHKCDITLQEIIKTLNSLTEQKTLCTELTVTDIFAAS
  KNTTEKETFCRAATVLRQFYSHHEKDTRCLGATAQQFHRHKQLIRFLKRLDRNLWGLAGL
  NSCPVKEANQSTLENFLERLKTIMREKYSKCSS
• Function: It is a costimulator of DNA-synthesis. It induces the expression of class II MHC molecules on resting B-cells. It enhances both secretion and cell surface expression of IgE and IgG1. It also regulates the expression of the low affinity Fc receptor for IgE (CD23) on both lymphocytes and monocytes. Positively regulates IL31RA expression in macrophages. Stimulates autophagy in dendritic cells by interfering with mTORC1 signaling and through the induction of RUFY4. Participates in at least several B-cell activation processes as well as of other cell types.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  PI3K-Akt signaling pathway (hsa04151)
  Jak-STAT signaling pathway (hsa04630)
  Hematopoietic cell lineage (hsa04640)
  T cell receptor signaling pathway (hsa04660)
  Fc epsilon RI signaling pathway (hsa04664)
  Intestinal immune network for IgA production (hsa04672)
  Leishmaniasis (hsa05140)
  Measles (hsa05162)
  Asthma (hsa05310)
  Autoimmune thyroid disease (hsa05320)
  Inflammatory bowel disease (IBD) (hsa05321)
  Allograft rejection (hsa05330)
• Reactome Pathway:
  Interleukin-18 signaling (R-HSA-9012546)
  Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)

Molecular Interaction Atlas (MIA) of This DTT

9 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dexpramipexole	DM6KXAU	Eosinophilic asthma	CB02.0	Phase 3	[2]
IL-4R	DMYEGRH	N. A.	N. A.	Phase 2	[1]
Pascolizumab	DMU3XJP	Asthma	CA23	Phase 2	[3]
PEGylated pitrakinra	DMBPJ9U	Asthma	CA23	Phase 2	[3]
Romilkimab	DMYEZ5J	Idiopathic pulmonary fibrosis	CB03.4	Phase 2	[4]
SAR-156597	DMUICJD	Idiopathic pulmonary fibrosis	CB03.4	Phase 2	[5]
Tepoxalin	DMVS61L	Asthma	CA23	Phase 2	[6]
PF-07264660	DM0GI2H	Atopic dermatitis	EA80	Phase 1	[7]
PF-07275315	DMHRVUY	Atopic dermatitis	EA80	Phase 1	[7]

References

• [1] Efficacy of soluble IL-4 receptor for the treatment of adults with asthma. J Allergy Clin Immunol. 2001 Jun;107(6):963-70.
• [2] Therapeutic strategies for eosinophilic dermatoses. Curr Opin Pharmacol. 2019 Jun;46:29-33.
• [3] The potential of biologics for the treatment of asthma. Nat Rev Drug Discov. 2012 Dec;11(12):958-72.
• [4] A randomised, double-blind, placebo-controlled, 24-week, phase II, proof-of-concept study of romilkimab (SAR156597) in early diffuse cutaneous systemic sclerosis. Ann Rheum Dis. 2020 Dec;79(12):1600-1607.
• [5] Bispecific antibodies rise again. Nat Rev Drug Discov. 2014 Nov;13(11):799-801.
• [6] Therapeutic interference with interferon-gamma (IFN-gamma) and soluble IL-4 receptor (sIL-4R) in allergic diseases. Behring Inst Mitt. 1995 Jun;(96):118-30.
• [7] Clinical pipeline report, company report or official report of Pfizer