Design, synthesis and biological evaluation of sulfonylurea derivatives as NLRP3 inflammasome inhibitors.

The NLRP3 inflammasome has been extensively studied in recent years and its aberrant activation can exacerbate inflammatory responses, contributing to various diseases. MCC950, a sulfonylurea drug, is a potent selective inhibitor of the NLRP3 inflammasome. However, its clinical development was halted due to hepatotoxicity, and studies have indicated significant reduction in activity among its metabolites.

CCDC6-RET fusion protein regulates Ras/MAPK signaling through the fusion- GRB2-SHC1 signal niche.

Rearranged during transfection (RET) rearrangement oncoprotein-mediated Ras/MAPK signaling cascade is constitutively activated in cancers. Here, we demonstrate a unique signal niche. The niche is a ternary complex based on the chimeric RET liquid-liquid phase separation.

Total synthesis/semi-synthesis of natural isopentenyl flavonoids with inhibitory activity on NLRP3 inflammasome.

Inflammation is the body's defense response to stimuli. When the homeostatic balance is disturbed, disease may result. Flavonoids have clear anti-inflammatory effects and the isopentenyl group significantly enhances the pharmacological activity of flavonoids.

Small Molecule Inhibitors as Therapeutic Agents Targeting Oncogenic Fusion Proteins: Current Status and Clinical.

Oncogenic fusion proteins, arising from chromosomal rearrangements, have emerged as prominent drivers of tumorigenesis and crucial therapeutic targets in cancer research. In recent years, the potential of small molecular inhibitors in selectively targeting fusion proteins has exhibited significant prospects, offering a novel approach to combat malignancies harboring these aberrant molecular entities. This review provides a comprehensive overview of the current state of small molecular inhibitors as therapeutic agents for oncogenic fusion proteins.

Role of Histone Post-Translational Modifications in Inflammatory Diseases.

Inflammation is a defensive reaction for external stimuli to the human body and generally accompanied by immune responses, which is associated with multiple diseases such as atherosclerosis, type 2 diabetes, Alzheimer's disease, psoriasis, asthma, chronic lung diseases, inflammatory bowel disease, and multiple virus-associated diseases. Epigenetic mechanisms have been demonstrated to play a key role in the regulation of inflammation. Common epigenetic regulations are DNA methylation, histone modifications, and non-coding RNA expression; among these, histone modifications embrace various post-modifications including acetylation, methylation, phosphorylation, ubiquitination, and ADP ribosylation.

Huoshanmycins A‒C, New Polyketide Dimers Produced by Endophytic sp. HS-3-L-1 From .

Three new polyketide dimers named huoshanmycins A‒C (-) were isolated from a plant endophytic sp. HS-3-L-1 in the leaf of , which was collected from the Cultivation base in Jiuxianzun Huoshanshihu Co., Ltd.

The protonation state of Glu202 in acetylcholinesterase.

Acetylcholinesterase (AChE) is the crucial enzyme in the central nervous system. It is the target of various organophosphorus nerve agents and pesticides, and the inhibition of AChE is a therapeutic strategy for the treatment of various neurological-related diseases. The Glu202 is a key residue adjacent to the catalytic His447 and plays important role in catalysis.

Terragines F-G produced by endophytic sp. SH-1.2-ROOT-18 from .

Two new terragine analogs (‒) with special succinimide and aminopentane moieties were isolated from the fermentation broth of sp. SH-1.2-ROOT-18, an endophyte previously discovered from the root of .

New peptidendrocins and anticancer chartreusin from an endophytic bacterium of .

Background: Endophyte has now become a potential source for the discovery of novel natural products, as they participate in biochemical pathways of their hosts and produce analogous or novel bioactive compounds. As an epiphytic plant, is one of precious Chinese medicines with various activities. It is well known for containing diverse endophytes, but so far not much is known about their secondary metabolites.

Evaluation of the cholinesterase activity of a potential therapeutic cocaine esterase for cocaine overdose.

Background: Cocaine is a commonly abused drug and there is no approved medication specifically to treat its addiction or overdose. Bacterial cocaine esterase (CocE)-derived RBP-8000 is currently under clinical development for cocaine overdose treatment. It is proven to be effective for human use to accelerate cocaine metabolism into physiologically inactive products.