Abstract
The heterodimeric cytokines IL-12 and IL-23 play a key role in T helper cell and innate lymphocyte cell differentiation and expansion. They are composed of a shared p40 chain, which pairs with a p35 or p19 chain to form IL-12 and IL-23, respectively. Preclinical model systems have predicted an important role of the p40 chain in intestinal inflammation. Moreover, genome-wide association studies have revealed that variants of the gene encoding the IL-23 receptor, as well as the locus harboring the gene encoding the p40 chain, confer genetic risk for developing Crohn’s disease (CD) and ulcerative colitis (UC). Two monoclonal antibodies neutralizing the p40 chain (ustekinumab and briakinumab) and hence blocking both IL-12 and IL-23 activity, have been developed, which demonstrated clinical benefit in early phase trials, and hinted towards efficacy in a subpopulation of patients with CD who had failed prior anti-TNF antibody treatment. A dedicated phase 3 clinical trial of ustekinumab in patients suffering from moderate-to-severe CD who had previously failed anti-TNF antibody treatment indeed demonstrated a significant benefit over placebo for clinical response, but not remission, in this particularly difficult to treat patient population. Here we review the immunological and genetic background to anti-IL-12/IL-23-directed therapeutic strategies, and the lessons that can be learned from results of these and related clinical trials that tackle associated biological pathways.
Keywords: Briakinumab, Crohn’s disease, inflammatory bowel disease, interleukin-12, interleukin-23, ulcerative colitis, ustekinumab.
Call for Papers in Thematic Issues
Drug-Targeted Approach with Polymer Nanocomposites for Improved Therapeutics
Polymer nanocomposites have been recognized as an advanced and cutting-edge technique in drug targeting administration. These materials combine the unique features of nanoparticles with the adaptability of polymers to produce highly personalized drug administration devices. Integrating nanoparticles containing pharmaceuticals into a polymer matrix enables researchers to regulate the rates at ...read more
New drug therapy for eye diseases
Eyesight is one of the most critical senses, accounting for over 80% of our perceptions. Our quality of life might be significantly affected by eye disease, including glaucoma, diabetic retinopathy, dry eye, etc. Although the development of microinvasive ocular surgery reduces surgical complications and improves overall outcomes, medication therapy is ...read more
Therapeutic Chemical and RNA Design with Artificial Intelligence
Computer-Aided Drug Design (CADD) has emerged as a fundamental component of modern drug discovery. Molecular docking facilitates virtual screening on a large scale through structural simulations. However, traditional CADD approaches face significant limitations, as they can only screen known compounds from existing libraries. PubChem, as the most widely used chemical ...read more
Related Journals
Anti-Cancer Agents in Medicinal Chemistry
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry
Current Bioactive Compounds
Current Cancer Drug Targets
Combinatorial Chemistry & High Throughput Screening
Current Cancer Therapy Reviews
Current Diabetes Reviews
Current Drug Safety
Current Drug Therapy
Current Drug Delivery
Related Books
Anthocyanins: Pharmacology and Nutraceutical Importance
Computer-Aided Drug Discovery Methods: A Brief Introduction
The Roles and Responsibilities of Clinical Pharmacists in Hospital Settings
Bioactive Compounds from Medicinal Plants for Cancer Therapy and Chemoprevention
Drug Addiction Mechanisms in the Brain
Software and Programming Tools in Pharmaceutical Research
Objective Pharmaceutics: A Comprehensive Compilation of Questions and Answers for Pharmaceutics Exam Prep
Medicinal Chemistry of Drugs Affecting Cardiovascular and Endocrine Systems
Medicinal Plants, Phytomedicines and Traditional Herbal Remedies for Drug Discovery and Development against COVID-19
Advanced Pharmacy
85
