Four-repeat (4R)-tauopathies are neurodegenerative diseases whose main hallmarks are brain accumulations of specific protein tau isoforms that lead to syndromes such as progressive supranuclear palsy (PSP) or corticobasal syndrome. There are yet no sensitive-enough PET tracers for 4R-tauopathies.
Recent genome-wide association studies have elucidated a spliced variant (rs72613567:TA) in 17β-hydroxysteroid dehydrogenase 13 (HSD17B13) found to be associated with decreased risk of chronic liver disorders. The presence of this variant also correlates with delayed onset of autoimmune hepatitis in carriers.
Nonalcoholic steatohepatitis (NASH) is the most severe form of nonalcoholic fatty liver disease, where in addition to the accumulation of fat in the liver, there is also chronic inflammation and hepatocyte injury. With no therapy approved yet, selective thyroid hormone receptor-β (THR-β) agonism has yielded good results in ongoing clinical development.
Cyclophilins are a group of proteins involved in cell metabolism and homeostasis. One of the members, CypD, is located in mitochondria and plays an important role as a regulator of mitochondrial permeability transition (mPT) and necrotic cell death resulting in persistent mPT opening that, in turn, leads to hepatic ischemia/reperfusion injury (IRI).
Merck & Co. Inc. has reported the development of a novel monobactam for use in combination with its class A/C β-lactamase inhibitor (BIL) relebactam (MK-7655) in order to achieve the broadest activity against multidrug-resistant (MDR) gram-negative pathogens that express a variety of β-lactamases. The in vitro efficacy of the combination of the monobactam – MSD-045934942 – against a panel of MDR and non-MDR gram-negative bacteria was evaluated using in vitro broth microdilution testing.
Current treatments for Graves’ hyperthyroidism (GH) and Graves’ orbitopathy (GO) are ineffective. Researchers assessed the preclinical in vitro efficacy of SYD-5115 (Byondis BV), a novel low-molecular-weight thyrotropin receptor (TSH-R) antagonist. The compound comprises an N-acetylated dihydropyrrole pyrimidine core with various substituents, including a difluorinated-spirocyclohexyl ring and a chiral carbamate group on the pyrimidine ring.
Having demonstrated in previous work that drug-Fc conjugates (DFCs) are a promising treatment alternative for multidrug-resistant (MDR) gram-negative bacteria, researchers from the Center for Discovery and Innovation and Cidara Therapeutics Inc. presented results from the identification of CTC-177, a novel DFC, as a potential immunoprophylactic agent against MDR gram-negative bacterial infections.
Son of sevenless 1 (SOS1) is a guanine exchange factor (GEF) primarily responsible for linking cell-surface receptors to RAS protein activation converting the inactive form of GDP-loaded RAS proteins into the active GTP-loaded RAS. This role together with its function in inhibiting MAPK pathway reactivation suggest that SOS1 may be a therapeutic target to treat KRAS-driven cancers.
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