Overcoming Resistance to FLT3-ITD Therapeutics.

FLT3-ITD (internal tandem duplication) is a key driver of acute myeloid leukemia (AML), and several FDA-approved drugs target this mutant kinase. This Viewpoint describes the discovery of inhibitors targeting point mutants and the development of SILA123, a highly potent and selective type II FLT3 inhibitor. In studies, SILA-123 significantly suppressed tumor growth in allograft models, demonstrating its potential in treating resistant AML.

A highly potent bi-thiazole inhibitor of LOX rewires collagen architecture and enhances chemoresponse in triple-negative breast cancer.

Lysyl oxidase (LOX) is upregulated in highly stiff aggressive tumors, correlating with metastasis, resistance, and worse survival; however, there are currently no potent, safe, and orally bioavailable small molecule LOX inhibitors to treat these aggressive desmoplastic solid tumors in clinics. Here we discovered bi-thiazole derivatives as potent LOX inhibitors by robust screening of drug-like molecules combined with cell/recombinant protein-based assays. Structure-activity relationship analysis identified a potent lead compound (LXG6403) with ∼3.

Virus-like particles of louping ill virus elicit potent neutralizing antibodies targeting multimers of viral envelope protein.

Louping ill virus (LIV) is a tick-borne flavivirus that predominantly causes disease in livestock, especially sheep in the British Isles. A preventive vaccine, previously approved for veterinary use but now discontinued, was based on an inactivated whole virion that likely provided protection by induction of neutralizing antibodies recognizing the viral envelope (E) protein. A major disadvantage of the inactivated vaccine was the need for high containment facilities for the propagation of infectious virus, as mandated by the hazard group 3 status of the virus.

A qualitative study of young peoples' thoughts and attitudes to follow a more plant-based diet.

Plant-based diets (PBDs) refer to dietary habits that reduce the consumption of animal-based products and increase the consumption of nutritionally rich plant foods. PBD's have been shown to provide significant health benefits, such as reducing obesity and improving psychological wellbeing, and are environmentally friendly. However, few studies have investigated factors that influence young people's thoughts and attitudes toward following a PBD in western societies, particularly in the United Kingdom.