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Your Position: Home > Insights > [Inspiring Target] IL-4R Alpha, a Potential Drug Target Worth over $10 Billion
[Inspiring Target] IL-4R Alpha, a Potential Drug Target Worth over $10 Billion
Release time: 2022-08-10 Source: ACROBiosystems Read: 6977


Interleukin-4 receptor (IL-4R) has emerged as an ‘inspiring’ target for innovative therapies aimed at treating atopic diseases. This type-1 transmembrane protein plays a key role in the molecular pathway that drives a specific immune response pattern called type-2 inflammations. These inflammations are the root cause of several medical conditions including atopic dermatitis (AD) and certain types of asthma. A brief understanding the molecular pathway behind this immune response pattern is fundamental to elucidating the mechanism of drug action and recognizing the immense potential behind IL-4R alpha targeting drugs.

IL-4R cellular pathway

IL-4R cellular pathway

IL-4 and IL-13 are cytokines that have diverse biological and immunological effects on B-lymphocytes, monocytes, dendritic cells, and fibroblasts’ adjustment function. These cytokines bind to IL-4R alpha and IL-13R alpha to initiate the type-2 inflammation pathway that includes differentiation of Th2 cells, airway inflammation, and mucus production. In cases of allergic diseases such as AD, the type-2 inflammation pathway is first initiated by an abnormal secretion of cytokines stemming from an imbalance of Th1 and Th2 differentiation. Activated Th2 cells release cytokines including IL-4, 13, and 31, which activate downstream B cells to transform and produce IgE antibodies. In turn, mast cells and basophils are recruited to degranulate and produce inflammatory factors. Simultaneously, the secreted IL-4 and 13 continue to bind to its respective receptors (e. g. IL-4R) that repeatedly promotes TH2 differentiation and subsequent inflammation.

The signaling role of IL-4 and IL-13 in the type-2 inflammation pathway reveals IL-4R alpha as a prospective target for patients with abnormal type-2 inflammation responses. Unlike the single-target functions of drugs targeting IL-4 and IL-13 specifically, IL-4R alpha has an innovative mechanism similar to ‘bi-specific’ targets. Antibodies targeting IL-4R alpha prevents the binding of both IL-4 and IL-13 which blocks intracellular signaling, thereby regulating immune function through inhibition of Th2 cell differentiation, IgE synthesis, and inflammatory substances secretion. As a result, many pharmaceutical companies around the world have emphasized the development of IL-4R targeting-drugs in their pipelines.

Advances in drug research and development targeting IL-4R alpha (Sourced from Pharmacodia)

Drug NameHighest StageCompanyIndications
DupilumabLaunched (2017)Sanofi/Regeneron Eosinophilic Esophagitis; Atopic Dermatitis;
Sinusitis; Nasal Polyps; Asthma
CM-310Phase IIIKeymed Biosciences
     CSPC Pharmaceutical
Sinusitis; Nasal Polyps; Atopic Dermatitis; Pruritus;
Solid Tumors; Asthma; Nasal Disorders; Allergic Rhinitis
Recombinant anti-IL-4Rα humanized monoclonal antibodyPhase IISunshine GuojianAtopic Dermatitis
Dragon Boat Pharmaceutical
Atopic Dermatitis; Asthma
ManfidokimabPhase II
Akeso Pharmaceuticals
Atopic Dermatitis; Asthma
QX-005NPhase IIQyuns TherapeuticsAtopic Dermatitis; Prurigo; Asthma;
Chronic Urticaria; Sinusitis
ElarekibepPhase IIAstraZeneca
     Pieris Australia Pty Ltd
CBP-201Phase IIConnect BiopharmaAtopic Dermatitis; Asthma
SHR-1819Phase IAtridia Pty Ltd;
     Jiangsu Hengrui Pharmaceuticals
Atopic Dermatitis; Asthma
LQ-036Phase IShanghai Novamab Biopharmaceuticals;
Syneos Health
BA2101PreclinicalBoan BiotechAtopic Dermatitis; Asthma;
Sinusitis;Itching; Hives

Currently, the only IL-4R alpha targeting drug available on the market is Dupilumab, which was jointly developed by Sanofi and Regeneron. In 2020, sales for Dupilumab exceeded $4 billion, with projections of over $10 billion by 2024. One of the main targets for Dupilumab is AD, otherwise known as eczema, which is a prevalent disease that affects millions of people. According to epidemiologic statistics from Frost & Sullivan, the number of patients suffering from AD has reached 649 million and is predicted to increase to 755 million people globally. Current first-line treatment for moderate-to-severe AD involves the use of topical creams and ointments to manage the severity of itching. However, for patients with uncontrolled AD, Dupilumab manages the inflammation before it even begins by inhibiting the inflammation signaling pathway. Its effectiveness has resulted in a multi-disciplinary consensus statement that emphasizes the use of Dupilumab as a first-line systemic treatment modality when topical therapy is ineffective. The success of Dupilumab in controlling severe cases of AD has helped broaden its clinical applications into other medical conditions including eosinophilic esophagitis, sinusitis, and certain cases of asthma.

Mechanism of Action of Dupilumab

Mechanism of Action of Dupilumab

Overall, IL-4R alpha is an extremely promising therapeutic target for the management and treatment of atopic diseases. ACROBiosystems has specially launched a series of IL-4R alpha/ IL-4/ IL-13 recombinant proteins, which are suitable for antibody screening and functional verification, to support the research and development of IL-4R alpha targeted drugs.

Product Features

Expressed by HEK293 cells – Recombinant proteins close to native conformation

Various species available – Human, Mouse, Cynomolgus / Rhesus macaque

Several tags offered – His & Avi Tag, His Tag, Fc Tag, Fc & Avi Tag

High purity and structural homogeneity – Verified by SDS-PAGE and SEC-MALS

High bioactivity – Verified by ELISA binding and competition experiments

Product List
MoleculeCat. No.SpeciesProduct Description
IL-4 R alphaILR-H5221HumanHuman IL-4 R alpha / CD124 Protein, His Tag
ILR-H82E9HumanBiotinylated Human IL-4 R alpha / CD124 Protein, Avitag™, His Tag
ILR-H5253HumanHuman IL-4 R alpha / CD124 Protein, Fc Tag
ILR-H82F4HumanBiotinylated Human IL-4 R alpha / CD124 Protein, Fc, Avitag™
ILR-M5252MouseMouse IL-4 R alpha / CD124 Protein, Fc Tag
ILR-M52H1MouseMouse IL-4 R alpha / CD124 Protein, His Tag
ILR-C5258Cynomolgus / Rhesus macaqueCynomolgus / Rhesus    macaque IL-4 R alpha / CD124 Protein, Fc Tag
ILR-C52H8Cynomolgus / Rhesus macaqueCynomolgus / Rhesus macaque IL-4 R alpha / CD124 Protein, His Tag
IL-4IL4-H4218HumanActiveMax® Human IL-4 Protein, Tag Free
IL4-H82E0HumanBiotinylated Human IL-4 Protein, Avitag™, His Tag
IL4-H52H9HumanHuman IL-4 Protein, His Tag (MALS verified)
IL4-M52H5MouseMouse IL-4 Protein, His Tag
IL4-C5259CynomolgusCynomolgus IL-4 Protein, Fc Tag (MALS verified)
IL-13IL3-H52H4HumanHuman IL-13 Protein, His Tag
IL3-H5256HumanHuman IL-13 Protein, Fc Tag
IL3-H82E5HumanBiotinylated Human IL-13 Protein, His, Avitag™
IL3-C52H4CanineCanine IL-13 Protein, His Tag

Learn More About Our Featured Interleukins Products

IL-2 and IL-2 Receptors

IL-2 and IL-2 Receptors

IL-2, IL-2R α, IL-2 R βγ, IL-2R αβγ

Affinity verified by SPR (Biacore)

IL-6 and IL-6 Receptors

IL-6 and IL-6 Receptors

IL-6, IL-6 R alpha, gp130

ELISA/BLI/cell-based assay verified

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1. C. K. Oh, G. P. Geba, N. Molfino. Investigational therapeutics targeting the IL-4/IL-13/STAT-6 pathway for the treatment of asthma. European Respiratory Review 19, 46-54 (2010). DOI: 10.1183/09059180.00007609

2. Licari, A., Castagnoli, R., Marseglia, A. et al. Dupilumab to Treat Type 2 Inflammatory Diseases in Children and Adolescents. Pediatr Drugs 22, 295–310 (2020).

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