Development of Potent and Selective CK1α Molecular Glue Degraders.

Molecular glue degraders (MGDs) are small molecules that facilitate proximity between a target protein and an E3 ubiquitin ligase, thereby inducing target protein degradation. Glutarimide-containing compounds are MGDs that bind cereblon (CRBN) and recruit neosubstrates. Through explorative synthesis of a glutarimide-based library, we discovered a series of molecules that induce casein kinase 1 alpha (CK1α) degradation.

Potassium-telluroether interactions: structural characterisation and computational analysis.

Dissolution of the potassium complex [K(ATe)(dme)] (1-Te) in THF, layering with hexanes, and cooling to -30 °C afforded X-ray quality crystals of [K(ATe)(THF)] (2-Te). The K-TeR distances in 2-Te are substantially shorter than those in 1-Te, and DFT and QTAIM calculations support the presence of K-TeR interactions, providing the first unambiguous examples of s-block-telluroether bonding. Attempts to prepare bulk quantities of 2-Te afforded [K(ATe)(THF)] (3-Te), and further drying yielded [K(ATe)(THF)] (4-Te) and [K(ATe)] (5-Te).

Multi-Omics Analysis in Mouse Primary Cortical Neurons Reveals Complex Positive and Negative Biological Interactions Between Constituent Compounds of .

A water extract of the Ayurvedic plant (L.) Urban, family Apiaceae (CAW), improves cognitive function in mouse models of aging and Alzheimer's disease and affects dendritic arborization, mitochondrial activity, and oxidative stress in mouse primary neurons. Triterpenes (TT) and caffeoylquinic acids (CQA) are constituents associated with these bioactivities of CAW, although little is known about how interactions between these compounds contribute to the plant's therapeutic benefit.

Peripheral Blood DNA Methylation Changes in Response to Treatment in Aged Mice.

Alterations in epigenetic modifications, like DNA methylation, in peripheral blood could serve as a useful, minimally invasive biomarker of the effects of anti-aging interventions. This study explores this potential with a water extract of the botanical (CAW). Eighteen-month-old mice were treated with CAW in their drinking water for 5 weeks alongside vehicle-treated eighteen-month-old C57BL6 mice.

The CD74 inhibitor DRhQ improves short-term memory and mitochondrial function in 5xFAD mouse model of Aβ accumulation.

Neuroinflammation and mitochondrial dysfunction are early events in Alzheimer's disease (AD) and contribute to neurodegeneration and cognitive impairment. Evidence suggests that the inflammatory axis mediated by macrophage migration inhibitory factor (MIF) binding to its receptor, CD74, plays an important role in many central nervous system (CNS) disorders such as AD. Our group has developed DRhQ, a novel CD74 binding construct which competitively inhibits MIF binding, blocks macrophage activation and migration into the CNS, enhances anti-inflammatory microglia cell numbers and reduces pro-inflammatory gene expression.