Targeted degradation of the HPV oncoprotein E6 reduces tumor burden in cervical cancer.

Human Papilloma Virus (HPV)-related cancers are a global health burden, yet there are no targeted therapies available for chronically infected patients. The HPV protein E6 is essential for HPV-mediated tumorigenesis and immune evasion, making it an attractive target for antiviral drug development. In this study, we developed an E6-targeting Proteolysis Targeting Chimera (PROTAC) that inhibits the growth of HPV(+) tumors.

Structural basis for FN3K-mediated protein deglycation.

Protein glycation is a universal, non-enzymatic modification that occurs when a sugar covalently attaches to a primary amine. These spontaneous modifications may have deleterious or regulatory effects on protein function, and their removal is mediated by the conserved metabolic kinase fructosamine-3-kinase (FN3K). Despite its crucial role in protein repair, we currently have a poor understanding of how FN3K engages or phosphorylates its substrates.

Structural perspectives on recent breakthrough efforts toward direct drugging of RAS and acquired resistance.

The Kirsten rat sarcoma viral oncoprotein homolog (KRAS) is currently a primary focus of oncologists and translational scientists, driven by exciting results with KRAS-targeted therapies for non-small cell lung cancer (NSCLC) patients. While KRAS mutations continue to drive high cancer diagnosis and death, researchers have developed unique strategies to target KRAS variations. Having been investigated over the past 40 years and considered "undruggable" due to the lack of pharmacological binding pockets, recent breakthroughs and accelerated FDA approval of the first covalent inhibitors targeting KRAS, have largely sparked further drug development.

Tuaimenals B-H, Merosesquiterpenes from the Irish Deep-Sea Soft Coral with Bioactivity against Cervical Cancer Cell Lines.

Previous chemical investigation of the Irish deep-sea soft coral led to the identification of tuaimenal A (), a new merosesquiterpene containing a highly substituted chromene core and modest cytotoxicity against cervical cancer. Further MS/MS and NMR-guided investigation of this octocoral has resulted in the isolation and characterization of seven additional tuaimenal analogs, B-H (-), as well as two known A-ring aromatized steroids (, ), and additional tuaimenal A (). Tuaimenals B, F, and G (, , ), bearing an oxygen at the C position, as well as monocyclic tuaimenal H (), show increased cervical cancer inhibition profiles in comparison to that of .