At The Interface: Small-Molecule Inhibitors of Soluble Cytokines DOI

Raavi,

Angela N. Koehler, Arturo J. Vegas

et al.

Chemical Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: April 15, 2025

Cytokines are crucial regulators of the immune system that orchestrate interactions between cells and, when dysregulated, contribute to progression chronic inflammation, cancer, and autoimmunity. Numerous biologic-based clinical agents, mostly monoclonal antibodies, have validated cytokines as important targets now part standard care for a number diseases. These while impactful, still suffer from limitations including lack oral bioavailability, high cost production, immunogenicity. Small-molecule cytokine inhibitors attractive alternatives can address these limitations. Although targeting cytokine-cytokine receptor complexes with small molecules has been challenging research endeavor, multiple small-molecule identified, them undergoing evaluation. In this review, we highlight recent advancements in discovery development soluble cytokines. The strategies identifying novel ligands well structural mechanistic insights into their activity represent milestones tackling clinically protein-protein interactions.

Language: Английский

Tackling TNF-α in autoinflammatory disorders and autoimmune diseases: From conventional to cutting edge in biologics and RNA- based nanomedicines DOI Creative Commons
Valentina Andretto, Silvia Dusi, Serena Zilio

et al.

Advanced Drug Delivery Reviews, Journal Year: 2023, Volume and Issue: 201, P. 115080 - 115080

Published: Sept. 1, 2023

Language: Английский

Citations

18
The use of proteins and peptides-based therapy in managing and preventing pathogenic viruses DOI
Esmail M. El‐Fakharany, Hamada El‐Gendi, Ahmed K. Saleh

et al.

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 270, P. 132254 - 132254

Published: May 9, 2024

Language: Английский

Citations

8
Immune-Mediated Diseases from the Point of View of Psychoneuroimmunoendocrinology DOI Creative Commons
Miguel Á. Ortega, Cielo García‐Montero, Oscar Fraile‐Martínez

et al.

Biology, Journal Year: 2022, Volume and Issue: 11(7), P. 973 - 973

Published: June 28, 2022

Immune-mediated inflammatory diseases (IMIDs) represent a large group of (Crohn's, ulcerative colitis, psoriasis, lupus, and rheumatoid arthritis) evidenced by systemic inflammation multiorgan involvement. IMIDs result in reduced quality life an economic burden for individuals, health care systems, countries. In this brief descriptive review, we will focus on some the common biological pathways these from point view psychoneuroimmunoendocrinology (PNIE). PNIE consists four medical disciplines (psychology, nervous system, immune endocrine system), which are key drivers behind health-disease concept that human being functions as unit. We examine emphasize need integrative treatments addresses disease psychosomatic view.

Language: Английский

Citations

24
Subcutaneous Infliximab [CT-P13], a True Biologic 2.0. Real Clinical Practice Multicentre Study DOI Creative Commons
José María Huguet, V. García,

Lidia Martí

et al.

Biomedicines, Journal Year: 2022, Volume and Issue: 10(9), P. 2130 - 2130

Published: Aug. 30, 2022

Inflammatory bowel disease (IBD), including Crohn's and ulcerative colitis, is characterized by chronic relapsing intestinal inflammation. There are few data on the efficacy safety in clinical practice of infliximab (CT-P13) subcutaneous formulation (SC) for treatment patients with IBD.

Language: Английский

Citations

23
mRNA Lipid Nanoparticles for Ex Vivo Engineering of Immunosuppressive T Cells for Autoimmunity Therapies DOI
Ajay S. Thatte, Alex G. Hamilton,

Benjamin E. Nachod

et al.

Nano Letters, Journal Year: 2023, Volume and Issue: 23(22), P. 10179 - 10188

Published: Oct. 31, 2023

Cell-based therapies for autoimmune diseases have gained significant traction, with several approaches centered around the regulatory T (Treg) cell─a well-known immunosuppressive cell characterized by its expression of transcription factor Foxp3. Unfortunately, due to low numbers Treg cells available in circulation, harvesting and culturing remains a challenge. It has been reported that engineering Foxp3 CD4+ can result Treg-like phenotype; however, current methods inefficient these cells. Here, we develop an ionizable lipid nanoparticle (LNP) platform effectively deliver mRNA We successfully engineer into Foxp3-T (FP3T) transiently exhibit phenotype functionally suppress proliferation effector These results demonstrate promise LNP potential applications autoimmunity therapies.

Language: Английский

Citations

16
Therapeutic potential of TNFα inhibitors in chronic inflammatory disorders: Past and future DOI Creative Commons
Hongtao Zhang,

Nelson Shi,

Zhuo Diao

et al.

Genes & Diseases, Journal Year: 2020, Volume and Issue: 8(1), P. 38 - 47

Published: March 3, 2020

In the past 20 years, patients with rheumatoid arthritis (RA), Crohn's disease (CD), and other immune diseases have witnessed impact of a great treatment advance availability biological TNFα inhibitors. With 5 approved anti-TNFα biologics on market soon available biosimilars, more options benefited from understanding biology TNFα. Nevertheless, many unmet needs remain for people living TNFα-related diseases, namely some side effects tolerance current resistance to therapies. Furthermore, common such as osteoarthritis back/neck pain may respond therapies at early onset symptoms. Development new inhibitors focusing TNFR1 specific inhibitors, preferably small molecules that can be delivered orally, is much needed.

Language: Английский

Citations

35
Anti-Inflammatory Therapeutic Approaches to Prevent or Delay Post-Traumatic Osteoarthritis (PTOA) of the Knee Joint with a Focus on Sustained Delivery Approaches DOI Open Access

Christine M. Khella,

Judith M. Horvath,

Rojiar Asgarian

et al.

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(15), P. 8005 - 8005

Published: July 27, 2021

Inflammation plays a central role in the pathogenesis of knee PTOA after trauma. While comprehensive therapy capable preventing or delaying post-traumatic osteoarthritis (PTOA) progression joint injury does not yet clinically exist, current literature suggests that certain aspects early pathology may be prevented delayed by anti-inflammatory therapeutic interventions. We discuss multifaceted approaches effectively reducing continuous cycle inflammation and concomitant processes lead to cartilage degradation as well those can simultaneously promote intrinsic repair processes. Within this context, we focus on disease prevention, optimal timeframe treatment possible long-lasting sustained delivery local modes treatments could prevent joint-associated symptoms. Specifically, identify candidates are only but also anti-degenerative, anti-apoptotic pro-regenerative.

Language: Английский

Citations

32
Toward Overcoming Treatment Failure in Rheumatoid Arthritis DOI Creative Commons
Zhuqian Wang, Jie Huang, Duoli Xie

et al.

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Dec. 23, 2021

Rheumatoid arthritis (RA) is an autoimmune disorder characterized by inflammation and bone erosion. The exact mechanism of RA still unknown, but various immune cytokines, signaling pathways effector cells are involved. Disease-modifying antirheumatic drugs (DMARDs) commonly used in treatment classified into different categories. Nevertheless, based on a "trial-and-error" approach, substantial proportion patients show failed therapy for each DMARD. Over the past decades, great efforts have been made to overcome failure, including identification biomarkers, exploration reasons loss efficacy, development sequential or combinational DMARDs strategies approval new DMARDs. Here, we summarize these efforts, which would provide valuable insights accurate clinical medication. While gratifying, researchers realize that far from enough recommend specific individual patients. Precision medicine emerging medical model proposes highly individualized tailored approach disease management. In this review, also discuss potential precision overcoming with introduction cutting-edge technologies big data.

Language: Английский

Citations

32
Perspectives on Subcutaneous Infliximab for Rheumatic Diseases and Inflammatory Bowel Disease: Before, During, and After the COVID-19 Era DOI Creative Commons
Stefan Schreiber, Shomron Ben‐Horin, Rieke Alten

et al.

Advances in Therapy, Journal Year: 2022, Volume and Issue: 39(6), P. 2342 - 2364

Published: Jan. 6, 2022

The coronavirus disease 2019 (COVID-19) pandemic has prompted significant changes in patient care rheumatology and gastroenterology, with clinical guidance issued to manage ongoing therapy while minimising the risk of nosocomial infection for patients healthcare professionals (HCPs). Subcutaneous (SC) formulations biologics enable self-administer treatments at home; however, switching between agents may be undesirable. CT-P13 SC is first formulation infliximab that received regulatory approval termed a biobetter as it offers advantages over intravenous (IV) infliximab, including improved pharmacokinetics convenient mode delivery. Potential benefits terms reduced immunogenicity have also been suggested. With new formulation, provides an additional option dual which enables transition from IV administration route without changing agent. Before COVID-19, trials supported efficacy safety rheumatoid arthritis inflammatory bowel (IBD), selected on basis HCP preferences agents. During pandemic, rheumatic diseases IBD successfully switched some high levels satisfaction. As therapeutics, reduction resource requirements infusion services particularly welcome given facilitating reorganisation redeployment overstretched systems, alongside pharmacoeconomic exposure infection. Telemedicine contactless pushed forefront during lasting shift towards remote management community/home-based drug anticipated. supports implementation this paradigm future improvements value delivered. accumulation real-world data level confidence, patients, physicians, systems benefitting its uptake.

Language: Английский

Citations

22
Drug Repurposing to Target Neuroinflammation and Sensory Neuron-Dependent Pain DOI Creative Commons
Marco Sisignano, Philip Gribbon, Gerd Geißlinger

et al.

Drugs, Journal Year: 2022, Volume and Issue: 82(4), P. 357 - 373

Published: March 1, 2022

Around 20% of the American population have chronic pain and estimates in other Western countries report similar numbers. This represents a major challenge for global health care systems. Additional problems treatment persistent are comparably low efficacy existing therapies, failure to translate effects observed preclinical models human patients related setbacks clinical trials from previous attempts develop novel analgesics. Drug repurposing offers an alternative approach identify analgesics as it can bypass various steps classical drug development. In recent years, several approved drugs were attributed analgesic properties. Here, we review available data discuss findings suggesting that minocycline, fingolimod, pioglitazone, nilotinib, telmisartan, others, which originally developed different pathologies, analgesic, antihyperalgesic, or neuroprotective inflammatory neuropathic pain. For our analysis, subdivide into substances target neuroinflammation act on peripheral sensory neurons, highlight proposed mechanisms. Finally, merits challenges development

Language: Английский

Citations

21