A major contributor to obesity-related pathology is inflammation involving a shift in macrophage polarization toward the inflammatory M1 phenotype and accumulation of such macrophages in the liver and adipose tissue. Activation of Toll-like receptor 4 (TLR4) on macrophages leads the downstream adaptor protein MyD88 to promote M1 polarization through altered gene expression mediated by the transcription factor NF-κB.
At the recent European Respiratory Society meeting, researchers from 35Pharma Inc. presented data on HS-235, an activin receptor inhibitor designed to neutralize activins and growth differentiation factors (GDFs). Disorders such as heart failure (HF) and pulmonary hypertension (PH) are associated with dysregulated activin and GDFs without neutralizing bone morphogenetic proteins such as BMP-9 and BMP-10, which play key roles in lymphatic and vascular homeostasis.
Dem Biopharma Inc. has divulged G-protein coupled receptor 84 (GPR84) agonists and phagocytosis inducers reported to be useful for the treatment of cancer, infections, neurological disorders and rheumatoid arthritis.
Neuron23 Inc. has identified non-receptor tyrosine-protein kinase TYK2 inhibitors reported to be useful for the treatment of autoimmune disease, endocrine disorders, inflammatory disorders and multiple sclerosis.
Vanqua Bio Inc. has synthesized C5a anaphylatoxin chemotactic receptor 1 (C5aR; CD88) antagonists reported to be useful for the treatment of autoimmune disease, cancer, infections, and cardiovascular, inflammatory and neurological disorders.
Cogent Biosciences Inc. has disclosed prodrugs and their active metabolites acting as GTPase KRAS and their mutant inhibitors reported to be useful for the treatment of cancer.
Bacterial resistance remains one of the biggest obstacles to antibiotic efficacy and spurs the constant search for next-generation antimicrobials. Oxacins can kill bacteria by inhibiting the activity of DNA gyrase. As potential next-generation oxacin-like drugs, researchers at Southwest University and collaborators have developed thiazolylcyanovinyl benzopyridone acids, among which the ethyl compound [I] turned out to be effective at killing several gram-negative and -positive bacterial strains in vitro as well as Klebsiella pneumonia in biofilms. It also eliminated wound infection in mice, without causing obvious off-target toxicity.
Idiopathic pulmonary fibrosis (IPF) is a rapidly progressing lung disease with high unmet needs and characterized by an excess in matrix deposition that leads to severe decline in lung functioning, where arginase expression and arginine metabolism seem to be involved and could be a promising target. Astrazeneca has presented data regarding their arginase inhibitor, AZD-8965, for the potential treatment of IPF.
Vitiligo is caused by autoreactive CD8+ T cells that react against skin melanocytes, where IL-15 has been shown to activate these T cells. Innovent Biologics (Suzhou) Co. Ltd. recently presented data on their monoclonal antibody (mAb) – IBI-3013 – that targets IL-15. IBI-3013 was evaluated in vitro in immune cell expansion and CD8 T-cell activation assays, as well as in vivo in a skin inflammation model and in a graft-vs.-host disease (GVHD) model.
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