SMAC mimetics and RIPK inhibitors as therapeutics for chronic inflammatory diseases

New therapeutic approaches for chronic inflammatory diseases such as inflammatory bowel disease, rheumatoid arthritis, and psoriasis are needed because current treatments are often suboptimal in terms of both efficacy and the risks of serious adverse events. Inhibitor of apoptosis proteins (IAPs) are E3 ubiquitin ligases that inhibit cell death pathways and are themselves inhibited by second mitochondria-derived activator of caspases (SMAC). SMAC mimetics (SMs), small-molecule antagonists of IAPs, are being evaluated as cancer therapies in clinical trials. IAPs are also crucial regulators of inflammatory pathways because they influence both the activation of inflammatory genes and the induction of cell death through the receptor-interacting serine-threonine protein kinases (RIPKs), nuclear factor B (NF-B)–inducing kinase, and mitogen-activated protein kinases (MAPKs). Furthermore, there is an increasing interest in specifically targeting the substrates of IAP-mediated ubiquitylation, especially RIPK1, RIPK2, and RIPK3, as druggable nodes in inflammation control. Several studies have revealed an anti-inflammatory potential of RIPK inhibitors that either block inflammatory signaling or block the form of inflammatory cell death known as necroptosis. Expanding research on innate immune signaling through pattern recognition receptors that stimulate proinflammatory NF-B and MAPK signaling may further contribute to uncovering the complex molecular roles used by IAPs and downst...
Source: Signal Transduction Knowledge Environment - Category: Science Authors: Tags: STKE Reviews Source Type: news

Related Links:

This study combined the results of seven studies and compared the risk of melanoma among 34,000 patients treated with biologics and 135,000 patients treated with conventional systemic therapy for rheumatoid arthritis, psoriasis or inflammatory bowel disease.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news
HORSHAM, PA, April 24, 2020 – The Janssen Pharmaceutical Companies of Johnson &Johnson today announced the submission of two supplemental Biologics License Applications (sBLA) to the U.S. Food and Drug Administration (FDA) seeking approval of SIMPONI ARIA® (golimumab) for the treatment of polyarticular juvenile idiopathic arthritis (pJIA) and juvenile psoriatic arthritis (jPsA), in patients two years of age and older in combination with methotrexate. If approved for these indications, SIMPONI ARIA would be the first anti-tumor necrosis factor (TNF)-alpha biologic agent administered by intravenous infusion ava...
Source: Johnson and Johnson - Category: Pharmaceuticals Tags: Innovation Source Type: news
CONCLUSIONS: Patient-initiated appointment systems may have little or no effect on patient anxiety, depression and quality of life compared to consultant-led appointment systems. Other aspects of disease status and experience also appear to show little or no difference between patient-initiated and consultant-led appointment systems. Patient-initiated appointment systems may have little or no effect on service utilisation in terms of service contact and there is uncertainty about costs compared to consultant-led appointment systems. Patient-initiated appointment systems may have little or no effect on adverse events such a...
Source: Cochrane Database of Systematic Reviews - Category: General Medicine Authors: Tags: Cochrane Database Syst Rev Source Type: research
Hairy, scary, funny looking or pretty cool. The beasts in the Harry Potter universe are quite the diverse bunch with unique abilities and qualities. Just like new digital health tech targeted to fight autoimmune diseases or for the main part: their symptoms. Source: Warner Bros. Framestore The common ground for completely different illnesses like type 1 diabetes, inflammatory bowel disease, rheumatoid arthritis, and multiple sclerosis is an immune system disfunction. Immune cells and mechanisms target the body’s own cells and structures, deconstructing it bit by bit and inducing inflammation. An estim...
Source: The Medical Futurist - Category: Information Technology Authors: Tags: Biotechnology Future of Medicine chatbot diabetes digital health sleep optimization chronic pain chronic illness skin coronavirus autoimmune disease Source Type: blogs
Abstract New therapeutic approaches for chronic inflammatory diseases such as inflammatory bowel disease, rheumatoid arthritis, and psoriasis are needed because current treatments are often suboptimal in terms of both efficacy and the risks of serious adverse events. Inhibitor of apoptosis proteins (IAPs) are E3 ubiquitin ligases that inhibit cell death pathways and are themselves inhibited by second mitochondria-derived activator of caspases (SMAC). SMAC mimetics (SMs), small-molecule antagonists of IAPs, are being evaluated as cancer therapies in clinical trials. IAPs are also crucial regulators of inflammatory ...
Source: Science Signaling - Category: Biomedical Science Authors: Tags: Sci Signal Source Type: research
ConclusionOur findings indicate that flares or IRAEs occur frequently but are mostly manageable without ICI discontinuation in patients with a preexisting autoimmune disease. Immunosuppressive therapy at baseline is associated with poorer outcomes.
Source: Arthritis and Rheumatology - Category: Rheumatology Authors: Tags: Original Article Source Type: research
Publication date: Available online 15 November 2019Source: Autoimmunity ReviewsAuthor(s): José María G. Ruiz de Morales, Lluís Puig, Esteban Daudén, Juan D. Cañete, José Luis Pablos, Antonio Olveira Martín, Carlos González Juanatey, Alfredo Adán, Xavier Montalbán, Natalia Borruel, Guillermo Ortí, Esther Holgado Martín, Carolina García-Vidal, Cynthia Vizcaya Morales, Víctor Martín Vázquez, Miguel Ángel González-GayAbstractInterleukin 17 (IL-17) is a proinflammatory cytokine that has been the focus of...
Source: Autoimmunity Reviews - Category: Allergy & Immunology Source Type: research
Authors: Cui XF, Cui XG, Leng N Abstract Papillary renal cell carcinoma (PRCC) accounts for about 10 percent of all renal cell carcinomas, and the prognosis is poor for people with advanced disease. Interleukin-20 receptor subunit beta (IL20RB) is a single-pass type I membrane protein of the type II cytokine receptor family and is related to the pathogenesis of chronic inflammation and autoimmune diseases, including psoriasis, glaucoma, vitiligo, rheumatoid arthritis, and inflammatory bowel disease. However, little has been reported on IL20RB with respect to cancer, especially in PRCC. Thus, we performed this study...
Source: Journal of Toxicologic Pathology - Category: Toxicology Tags: J Toxicol Pathol Source Type: research
ConclusionThe occurrence of a flare/IRAE is frequent but mostly manageable without ICI discontinuation in patients with PAD. Immunosuppressive therapy at baseline was associated with poorer outcomes.This article is protected by copyright. All rights reserved.
Source: Arthritis and Rheumatology - Category: Rheumatology Authors: Tags: Full Length Source Type: research
Discussion MDSCs violently emerge in pathological conditions in an attempt to limit potentially harmful immune and inflammatory responses. Mechanisms supporting their expansion and survival are deeply investigated in cancer, in the perspective to reactivate specific antitumor responses and prevent their contribution to disease evolution. These findings will likely contribute to improve the targeting of MDSCs in anticancer immunotherapies, either alone or in combination with immune checkpoint inhibitors. New evidence indicates that the expansion of myeloid cell differentiation in pathology is subject to fine-tuning, as its...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
More News: Arthritis | Cancer | Cancer & Oncology | Cancer Therapy | Clinical Trials | Environmental Health | Genetics | Inflammatory Bowel Disease | Mitochondria | Psoriasis | Rheumatoid Arthritis | Rheumatology | Science | Study