Interferon regulatory factor 5 (IRF5) is a transcription factor activated downstream of Toll-like receptors (TLRs) 7, 8 and 9, and is predominantly expressed in dendritic cells, B cells, monocytes and macrophages. Once considered an undruggable target, IRF5 is now recognized as a key regulator of innate immunity, driving the production of type I interferons, pro-inflammatory cytokines and autoantibodies.
The OX40/OX40L costimulatory pathway is crucial for effective T-cell activation and is inducibly expressed in response to immunological stimulation. Targeting OX40L has demonstrated safety and efficacy in preclinical studies using nonhuman primate models of kidney and heart transplantation.
Degradation is a therapeutic strategy that could offer possibilities to get at currently undruggable target proteins. In targeted degradation, compounds induce interactions between a target protein and a protein that can tag the target for degradation. In principle, there are several pathways that could be used for such tagging; the most attention has gone to ubiquitin ligases, in particular cereblon, a protein that is part of a ubiquitin ligase complex and the target of several approved drugs.
Unnatural Products Inc. notched another collaboration by signing on with Argenx SE in a multitarget research collaboration. Unnatural Products, which is getting up-front, near-term payments and R&D funding, could end up with about $1.5 billion in milestones and options payments plus tiered royalties on net sales.
Agonists of immune checkpoint modulators for treating autoimmune and inflammatory disorders have shown high potential in immunotherapy. P-selectin glycoprotein ligand 1 (PSGL-1) is known to exert immune checkpoint regulator functions in T cells aside from its classic role as an adhesion molecule involved in leukocyte trafficking.
A healthy life for a healthy heart is a popular saying. However, even when following good habits, heart health can be already compromised from the very earliest stages of development. Maternal cells reach the embryo through the placenta contributing to its normal formation. So, just as the mother helps form a functional heart, she can also induce a condition that may not appear until adulthood.
VAV1 is a guanine nucleotide exchange factor essential for T- and B-cell receptor signaling, with expression largely restricted to immune cells. Loss of VAV1, via CRISPR or genetic deletion, impairs effector functions in both T and B cells.
Evaxion A/S has added a new vaccine program, named EVX-B4, to its pipeline for prevention of group A Streptococcus (GAS) infections. Invasive GAS infections can cause diseases such as sepsis, toxic shock, rheumatic heart disease and necrotizing fasciitis.
In multiple sclerosis (MS), an alteration of neuronal metabolism caused by dysfunction of its proteasome, the cellular machinery responsible for recycling proteins, contributes to neurodegeneration in this inflammatory disease. This finding could be explored for the development of drugs that protect neurons from damage in MS and other neurodegenerative disorders.
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