Interleukin-4 receptor (IL-4R): A drug target with massive potential

The interleukin-4 receptor (IL-4R) has become an “inspiring” target for cutting-edge treatments for atopic diseases. This type-1 transmembrane protein is essential to the molecular mechanism that underlies the type-2 inflammations, a particular pattern of the immune response.

Interleukin-4 receptor (IL-4R): A drug target with massive potential

Image Credit: ACROBiosystems

Atopic dermatitis (AD) and specific forms of asthma are two medical disorders that are mostly brought on by these inflammations. To fully comprehend the mechanism of therapeutic action and appreciate the enormous potential of IL-4R alpha targeting medicines, it is essential to have a basic understanding of the molecular process behind this immune response pattern.

Interleukin-4 receptor (IL-4R): A drug target with massive potential

IL-4R cellular pathway. Image Credit: ACROBiosystems

The biological and immunological functions of B-lymphocytes, monocytes, dendritic cells, and fibroblasts are all affected by the cytokines IL-4 and IL-13. These cytokines interact with the IL-4 and IL-13 receptors to start the type 2 inflammatory pathway, which results in Th2 cell differentiation, airway inflammation, and mucus production.

The type-2 inflammatory pathway is first activated in allergic illnesses like AD by aberrant cytokine release resulting from an imbalance of Th1 and Th2 differentiation. Th2 cells that have been activated release cytokines, including IL-4, 13, and 31, which prompt downstream B cells to undergo a change and produce IgE antibodies.

Mast cells and basophils are then called upon to degranulate and release inflammatory substances. Simultaneously, the secreted IL-4 and 13 continue to bind to its respective receptors, such as IL-4R, that repeatedly promotes TH2 differentiation and subsequent inflammation.

The type-2 inflammation pathway’s signaling role for IL-4 and IL-13 identifies IL-4R alpha as a potential target for individuals who exhibit aberrant type-2 inflammatory responses. Contrary to medications that target IL-4 and IL-13 exclusively, IL-4R alpha has a novel mechanism resembling “bi-specific” targets.

The immune system is controlled by antibodies that block the binding of both IL-4 and IL-13, which inhibits intracellular signaling and reduces the production of IgE, Th2 cell differentiation, and inflammatory substances. As a result, IL-4R targeting medication research has received a lot of attention from pharmaceutical companies all over the world.

Table 1. Advances in drug research and development targeting IL-4R alpha. Source: Pharmacodia

Drug Name Highest Stage Company Indications
Dupilumab Launched (2017) Sanofi/Regeneron Eosinophilic Esophagitis; Atopic Dermatitis;
Sinusitis; Nasal Polyps; Asthma
CM-310 Phase III Keymed Biosciences
CSPC Pharmaceutical
Sinusitis; Nasal Polyps; Atopic Dermatitis; Pruritus;
Solid Tumors; Asthma; Nasal Disorders; Allergic Rhinitis
Recombinant anti-IL-4Rα humanized monoclonal antibody Phase II Sunshine Guojian Atopic Dermatitis
Dragon Boat Pharmaceutical
Atopic Dermatitis; Asthma
Manfidokimab Phase II Akeso Pharmaceuticals Atopic Dermatitis; Asthma
QX-005N Phase II Qyuns Therapeutics Atopic Dermatitis; Prurigo; Asthma;
Chronic Urticaria; Sinusitis
Elarekibep Phase II AstraZeneca
Pieris Australia Pty Ltd
CBP-201 Phase II Connect Biopharma Atopic Dermatitis; Asthma
SHR-1819 Phase I Atridia Pty Ltd;
Jiangsu Hengrui Pharmaceuticals
Atopic Dermatitis; Asthma
LQ-036 Phase I Shanghai Novamab Biopharmaceuticals;
Syneos Health
BA2101 Preclinical Boan Biotech Atopic Dermatitis; Asthma;
Sinusitis;Itching; Hives


The only IL-4R alpha targeting medication on the market right now is Dupilumab, which was created in collaboration between Sanofi and Regeneron. Dupilumab sales surpassed $4 billion in 2020, and by 2024, they are expected to reach over $10 billion. 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 data from Frost & Sullivan, there are currently 649 million AD patients worldwide, and that number is expected to rise to 755 million by 2050. Topical creams and ointments are currently used as the first-line treatment for moderate-to-severe AD in order to control the level of itching. However, Dupilumab prevents inflammation from emerging in patients with uncontrolled AD by blocking the inflammation signaling system.

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 does not prove effective. The success of Dupilumab in controlling severe cases of AD has helped broaden its clinical applications to other medical conditions, including sinusitis, eosinophilic esophagitis, and specific cases of asthma.

Interleukin-4 receptor (IL-4R): A drug target with massive potential

Mechanism of Action of Dupilumab. Image Credit: ACROBiosystems

Ultimately, the therapeutic target of IL-4R alpha is very promising for the control and treatment of atopic diseases. To aid in the development of IL-4R alpha targeted therapeutics, ACROBiosystems has introduced a variety of IL-4R alpha/IL-4/IL-13 recombinant proteins that are ideal for antibody screening and functional verification.

Product features

  • Expressed by HEK293 cells — Recombinant proteins close to the native conformation
  • Availability of different species — Human, Mouse, Cynomolgus/Rhesus macaque
  • Numerous tags provided — His Tag, His & Avi Tag, Fc Tag, Fc & Avi Tag
  • High bioactivity — Verified by ELISA binding and competition experiments
  • High purity and structural homogeneity — Verified by SDS-PAGE and SEC-MALS

Product list

Table 2. Source: ACROBiosystems

Molecule Cat. No. Species Product Description
IL-4 R alpha ILR-H5221 Human Human IL-4 R alpha / CD124 Protein, His Tag
ILR-H82E9 Human Biotinylated Human IL-4 R alpha / CD124 Protein, Avitag™, His Tag
ILR-H5253 Human Human IL-4 R alpha / CD124 Protein, Fc Tag
ILR-H82F4 Human Biotinylated Human IL-4 R alpha / CD124 Protein, Fc, Avitag™
ILR-M5252 Mouse Mouse IL-4 R alpha / CD124 Protein, Fc Tag
ILR-M52H1 Mouse Mouse IL-4 R alpha / CD124 Protein, His Tag
ILR-C5258 Cynomolgus / Rhesus macaque Cynomolgus / Rhesus    macaque IL-4 R alpha / CD124 Protein, Fc Tag
ILR-C52H8 Cynomolgus / Rhesus macaque Cynomolgus / Rhesus macaque IL-4 R alpha / CD124 Protein, His Tag
IL-4 IL4-H4218 Human ActiveMax® Human IL-4 Protein, Tag Free
IL4-H82E0 Human Biotinylated Human IL-4 Protein, Avitag™, His Tag
IL4-H52H9 Human Human IL-4 Protein, His Tag (MALS verified)
IL4-M52H5 Mouse Mouse IL-4 Protein, His Tag
IL4-C5259 Cynomolgus Cynomolgus IL-4 Protein, Fc Tag (MALS verified)
IL-13 IL3-H52H4 Human Human IL-13 Protein, His Tag
IL3-H5256 Human Human IL-13 Protein, Fc Tag
IL3-H82E5 Human Biotinylated Human IL-13 Protein, His, Avitag™
IL3-C52H4 Canine Canine IL-13 Protein, His Tag


IL-2 and IL-2 receptors

Interleukin-4 receptor (IL-4R): A drug target with massive potential

Image Credit: ACROBiosystems

  • IL-2, IL-2 R βγ, IL-2R α, IL-2R αβγ
  • Affinity verified by SPR (Biacore)

IL-6 and IL-6 receptors

Interleukin-4 receptor (IL-4R): A drug target with massive potential

Image Credit: ACROBiosystems 

  • IL-6, IL-6 R alpha, gp130
  • ELISA/BLI/cell-based assay verified

Interleukin-4 receptor (IL-4R): A drug target with massive potential

Image Credit: ACROBiosystems


  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).

About ACROBiosystems

ACROBiosystems is a cornerstone enterprise of the pharmaceutical and biotechnology industries. Their mission is to help overcome challenges with innovative tools and solutions from discovery to the clinic. They supply life science tools designed to be used in discovery research and scalable to the clinical phase and beyond. By consistently adapting to new regulatory challenges and guidelines, ACROBiosystems delivers solutions, whether it comes through recombinant proteins, antibodies, assay kits, GMP-grade reagents, or custom services. ACROBiosystems empower scientists and engineers dedicated towards innovation to simplify and accelerate the development of new, better, and more affordable medicine.

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Last updated: Jan 30, 2024 at 4:13 AM


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