Exploration and structure-activity relationship research of benzenesulfonamide derivatives as potent TRPV4 inhibitors for treating acute lung injury.

RN-9893, a TRPV4 antagonist identified by Renovis Inc., showcased notable inhibition of TRPV4 channels. This research involved synthesizing and evaluating three series of RN-9893 analogues for their TRPV4 inhibitory efficacy.

The environmental sources of benzophenones: Distribution, pretreatment, analysis and removal techniques.

Benzophenones (BPs) have wide practical applications in real human life due to its presence in personal care products, UV-filters, drugs, food packaging bags, etc. It enters the wastewater by daily routine activities such as showering, impacting the whole aquatic system, then posing a threat to human health. Due to this fact, the monitoring and removal of BPs in the environment is quite important.

Discovery of highly potent and selective KRAS degraders by VHL-recruiting PROTACs for the treatment of tumors with KRAS-Mutation.

Although several covalent KRAS inhibitors have made great progress in the treatment of KRAS-mutant cancer, their clinical applications are limited by adaptive resistance, motivating novel therapeutic strategies. Through drug design and structure optimization, a series of highly potent and selective KRAS Proteolysis Targeting Chimeras (PROTACs) were developed by incorporating AMG510 and VHL ligand VH032. Among them, degrader YN14 significantly inhibited KRAS-dependent cancer cells growth with nanomolar IC and DC values, and ＞ 95 % maximum degradation (D).

Discovery of novel exceptionally potent and orally active c-MET PROTACs for the treatment of tumors with alterations.

Various c-mesenchymal-to-epithelial transition (c-MET) inhibitors are effective in the treatment of non-small cell lung cancer; however, the inevitable drug resistance remains a challenge, limiting their clinical efficacy. Therefore, novel strategies targeting c-MET are urgently required. Herein, through rational structure optimization, we obtained novel exceptionally potent and orally active c-MET proteolysis targeting chimeras (PROTACs) namely and based on thalidomide and tepotinib.