IL-23: A Key Target for the Treatment of Immune-Mediated Inflammatory Diseases

By Lauren He

June 24, 2026

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Structure and function of IL-23

IL-23 shares the p40 (β chain) subunit with IL-12; the p40 subunit binds with the IL-23p19 subunit (α chain) via disulfide bonds to form IL-23, and with the IL-12p35 subunit (α chain) to form IL-12. IL-12 and IL-23 conduct signaling through heterodimeric receptors, both of which contain IL-12 receptor β1 (IL-12Rβ1). IL-12Rβ1 binds with IL-12Rβ2 to form the IL-12 receptor, while IL-12Rβ1 binds with IL-23R to form the IL-23 receptor.

Structure of IL-23^[2]

Upon tissue injury or pathogen invasion, tissue-resident myeloid cells produce IL-23, which in turn promotes the proliferation and survival of T helper 17 (Th17) cells. Furthermore, IL-23 can activate other immune cells expressing IL-23 receptors and retinoic acid receptor-related orphan receptor γt (RORγt), including "natural" Th17 cells, IL-17 positive CD8+ T cells (Tc17 cells), as well as innate immune cells such as γδ T cells, natural killer T (NKT) cells, mucosal-associated invariant T (MAIT) cells, and IL-17-secreting innate lymphoid cells (ILC3), collectively known as type 17 cells.

IL-23 Producing Cells and Target Cells Involved in the Pathogenesis of PsO, PsA, and IBD^[1]

Upon binding to IL-23R on the surface of Th17 and type 17 cells, IL-23 activates Janus kinases (including JAK2 and TYK2), which bind to the intracellular domains of the receptor subunits and initiate a specific signaling cascade. This stimulates Th17 and type 17 cells to release pro-inflammatory cytokines such as IL-17A, IL-17F, IL-22, GM-CSF, IFN-γ, and TNF-α, triggering local tissue inflammation. In addition, IL-23 can activate transcription factors including signal transducer and activator of transcription 3 (STAT3), retinoic acid receptor-related orphan receptor γt (RORγt), and B lymphocyte-induced maturation protein-1 (Blimp-1) to enhance the expression of IL-23R. It also amplifies IL-23 signaling through a positive feedback loop while stabilizing the synthesis and secretion of pro-inflammatory effector molecules. Conversely, IL-12 promotes Th1 cell differentiation and activates NK cells, type 1 innate lymphoid cells (ILC1), and cytotoxic T cells to produce IFN-γ, TNF-α, granzymes, and perforin.

IL-23, IL-12 and their Receptors, Associated Effector Cells, Cytokines, and Immune Functions^[2]

Current Progress of IL-23 Targeted Drugs

As a key target for immune-mediated inflammatory diseases, IL-23 has attracted the layout of related targeted drugs by many domestic and foreign pharmaceutical companies. Currently, multiple drugs have been launched globally, mainly monoclonal antibodies, but targeting different subunits. The first-generation drugs target the p40 subunit, with the representative drug being Ustekinumab, which has been approved for marketing. This drug was first approved for the treatment of psoriasis in 2009, and in the field of inflammatory bowel disease, it has been used for Crohn's disease since 2016 and ulcerative colitis since 2019. The second-generation drugs precisely target the p19 subunit. The theoretical basis for their development is that the IL-12 mediated immune response is crucial for the body to defend against intracellular pathogens (e.g., inducing T cells and NK cells to release IFN-γ); by selectively targeting p19 while preserving the IL-12 mediated Th1 immune response, the body's immunity to various pathogens can be maintained^[3].

Johnson & Johnson's blockbuster drug Guselkumab is the world's first approved p19-targeted drug, initially approved in the US in July 2017 for the treatment of adult patients with moderate to severe plaque psoriasis. By May 2025, the approved indications for this drug in China have covered moderate to severe plaque psoriasis, moderate to severe active Crohn's disease, and moderate to severe active ulcerative colitis. The drug can not only effectively neutralize p19 but also bind to the CD64 receptor on IL-23 producing cells, exerting a dual inhibitory effect on inflammation. In October 2025, Johnson & Johnson disclosed the results of the GALAXI 2 and GALAXI 3 Phase 3 clinical trials of Guselkumab for the treatment of adult patients with moderate to severe active Crohn's disease. The results showed that Guselkumab intravenous induction followed by subcutaneous maintenance therapy was significantly superior to placebo in both short-term (W12) and long-term (W48) clinical and endoscopic efficacy for patients with moderate to severe active Crohn's disease. Compared with the positive control drug Ustekinumab, Guselkumab demonstrated statistical superiority in efficacy at week 48. Furthermore, up to 48 weeks, the drug showed a good safety profile, with a lower incidence of severe infections than Ustekinumab^[4].

Mechanism of Action of Guselkumab^[5]

Mirikizumab, developed by Eli Lilly, is an IgG4 monoclonal antibody that specifically targets the interleukin-23 (IL-23) p19 subunit, selectively blocking the IL-23 signaling pathway and thereby inhibiting intestinal inflammation. Currently, the drug has been approved for the treatment of moderate to severe active ulcerative colitis and Crohn's disease in countries and regions including Japan, the United States, the European Union, and China.

Mechanism of Action of Mirikizumab[6]

Drug Type	Drug	Target	Company	Highest Clinical Phase	Indications
mAb	Picankibart	IL-23p19	Innovent Biologics	Approved for Marketing	Plaque Psoriasis
mAb	Ebdarokimab	IL-12p40×IL-23	Akeso	Approved for Marketing	Plaque Psoriasis
mAb	Mirikizumab	IL-23p19	Eli Lilly	Approved for Marketing	Severe Active Crohn's Disease; Moderate Active Ulcerative Colitis; Crohn's Disease; Severe Active Ulcerative Colitis; Moderate Active Crohn's Disease
mAb	Risankizumab-RZAA	IL-23p19	AbbVie	Approved for Marketing	Moderate Active Ulcerative Colitis; Ulcerative Colitis; Plaque Psoriasis; Psoriatic Arthritis; Severe Active Ulcerative Colitis
mAb	Tildrakizumab-ASMN	IL-23p19	Merck & Co.; Sun Pharmaceutical; CMS	Approved for Marketing	Plaque Psoriasis
mAb	Guselkumab	IL-23p19	Janssen Pharmaceuticals	Approved for Marketing	Severe Active Crohn's Disease; Moderate Active Crohn's Disease; Plaque Psoriasis; Psoriatic Arthritis; Severe Active Ulcerative Colitis
mAb	Ustekinumab	IL-12p40	Janssen Pharmaceuticals	Approved for Marketing	Ulcerative Colitis; Crohn's Disease; Plaque Psoriasis; Psoriatic Arthritis

A selection of IL-23 targeted drugs

KACTUS High-Quality IL-23 Proteins

IL-23 has shown immense potential in the therapeutic field of immune-mediated inflammatory diseases, and the marketing approval of multiple drugs has brought diversified options for patients. KACTUS provides high-quality IL-23, p19 subunit, and IL-23R proteins. The products cover different species and various tag designs, and undergo strict quality control. They are suitable for various research and development needs such as immunization, screening, and epitope identification, helping to accelerate the R&D process of IL-23 targeted drugs.

Product Data

Immobilized Human IL-23 alpha&IL-12 beta, His Tag at 1 μg/ml (100 μl/well) on the plate. Dose response curve for Anti-IL-23 Antibody, hFc Tag with the EC50 of 3.3 ng/ml determined by ELISA.

Immobilized Human IL-23R, hFc Tag at 2 μg/ml (100 μl/well) on the plate. Dose response curve for Human IL-23 alpha&IL-12 beta, His Tag with the EC50 of 46.4ng/ml determined by ELISA (QC Test).

Immobilized Human IL-23 alpha, hFc Tag at 1μg/ml (100μl/well) on the plate. Dose response curve for Biotinylated Anti-IL-23 alpha Antibody, hFc Avi Tag with the EC50 of 43.2ng/ml determined by ELISA (QC Test).

Product List

Catalog Number	Product Name
IL2-HM1AB	Human IL-23 alpha&IL-12 beta, His Tag
IL2-HM1AB-UL	Human IL-23 alpha&IL-12 beta, Ultra Low Endotoxin, His Tag
IL2-HM4ABB	Biotinylated Human IL-23 alpha&IL-12 beta, His-Avi Tag
IL2-HM4ABB-UL	Biotinylated Human IL-23 alpha&IL-12 beta, Ultra Low Endotoxin, His-Avi Tag
ILB-HM4AB	Non-biotinylated Human IL-23 alpha&Mouse IL-12 beta, His-Avi Tag
ILB-HM4AB-UL	Non-biotinylated Human IL-23 alpha&Mouse IL-12 beta, Ultra Low Endotoxin, His-Avi Tag
ILB-HM4ABB	Biotinylated Human IL-23 alpha&Mouse IL-12 beta, His-Avi Tag
ILB-HM4ABB-UL	Biotinylated Human IL-23 alpha&Mouse IL-12 beta, Ultra Low Endotoxin, His-Avi Tag
IL2-MM1AB	Mouse IL-23 alpha&IL-12 beta, His Tag
IL2-MM1AB-UL	Mouse IL-23 alpha&IL-12 beta, Ultra Low Endotoxin, His Tag
IL2-CM123	Cynomolgus IL-23 alpha&IL-12 beta, His Tag
IL2-HM219	Human IL-23 alpha/IL-23 P19, hFc (IgG1) Tag
IL2-MM423B	Biotinylated Mouse IL-23 alpha/IL-23 P19, His-Avi Tag
IL2-CM1AB	Cynomolgus IL-23 alpha&Mouse IL-12 beta, His Tag
ILR-HM123	Human IL-23R, His Tag
ILR-HM223	Human IL-23R, hFc (IgG1) Tag
ILR-HM323	Human IL-23R, mFc Tag
ILR-HM323-UL	Human IL-23R, Ultra Low Endotoxin, mFc Tag
ILR-HM223B	Biotinylated Human IL-23R (Primary Amine Labeling), hFc (IgG1) Tag
ILR-MM123	Mouse IL-23R, His Tag
ILR-CM123	Cynomolgus IL-23R, His Tag
ILR-CM123-UL	Cynomolgus IL-23R, Ultra Low Endotoxin, His Tag
ILR-RM223	Rat IL-23R, hFc (IgG1) Tag
ILR-RM223-UL	Rat IL-23R, Ultra Low Endotoxin, hFc (IgG1) Tag
ILR-DM123	Canine IL-23R, His Tag
ILR-DM123-UL	Canine IL-23R, Ultra Low Endotoxin, His Tag

References

[1] Krueger JG, Eyerich K, Kuchroo VK, Ritchlin CT, Abreu MT, Elloso MM, Fourie A, Fakharzadeh S, Sherlock JP, Yang YW, Cua DJ, McInnes IB. IL-23 past, present, and future: a roadmap to advancing IL-23 science and therapy. Front Immunol. 2024 Apr 15;15:1331217. doi: 10.3389/fimmu.2024.1331217. PMID: 38686385; PMCID: PMC11056518.

[2] Ergen EN, Yusuf N. Inhibition of interleukin-12 and/or interleukin-23 for the treatment of psoriasis: What is the evidence for an effect on malignancy? Exp Dermatol. 2018 Jul;27(7):737-747. doi: 10.1111/exd.13676. PMID: 29704872; PMCID: PMC6023723.

[3] Fanizza J, D'Amico F, Lusetti F, Fasulo E, Allocca M, Furfaro F, Zilli A, Parigi TL, Radice S, Peyrin-Biroulet L, Danese S, Fiorino G. The Role of IL-23 Inhibitors in Crohn's Disease. J Clin Med. 2023 Dec 30;13(1):224. doi: 10.3390/jcm13010224. PMID: 38202231; PMCID: PMC10779938.

[4] efficacy-and-safety-of-guselkumab-induction-and-maintenance-therapy-in-patients-with-moderately-to-s.pdf

[5] MOA: Moderate to Severe Plaque PsO | TREMFYA® (guselkumab) HCP

[6] Colwill M, Baillie S, Clough J, Pollok R, Poullis A, Patel K, Honap S. Role of Mirikizumab in the Treatment of Inflammatory Bowel Disease-From Bench to Bedside. J Clin Med. 2025 Feb 5;14(3):1001. doi: 10.3390/jcm14031001. PMID: 39941671; PMCID: PMC11818495.