In the August issue of J. Antibiotics (Tokyo) Yoshida and coworkers at the University of Tsukuba reviewed their excellent work on synthesis, SAR, biology and chemical biology of the Destruxins, fungal cyclodepsipeptides from Metarhizium sp. They developed a practical synthesis using a macrolactonization strategy allowing gram scale production; synthesized 64 analogs; carried out SAR studies; …
Yan and coworkers have demonstrated a potential way to boost innate immune attack on solid tumors. They found that Rocaglamide, a structurally novel natural product, promoted tumor infiltration by NK cells through mitochondrial DNA damage and activation of the cGAS-STING signaling pathway.
Mitapivat is an allosteric activator of red blood cell pyruvate kinase, the enzyme that performs the final step of glycolysis: it catalyzes the conversion of phosphoenolpyruvate to pyruvate. Enzyme activators as drugs are very rare. After a Phase III clinical trial, it was approved by the FDA earlier this year as the first disease-modifying therapy …
Cancer cells modify their metabolism in order to survive and grow. For example, they employ the Warburg effect (increasing glucose uptake and directly converting it to lactate) to ultimately protect against accumulation of harmful reactive oxygen species (ROS). Since many of these altered pathways are unique to cancer cells, they are hot topics for cancer …
Lipid raft dynamics regulate signaling for multiple cellular functions, such as apoptosis, proliferation, and differentiation. They reside in the plasma membrane and comprise sphingolipids, cholesterol, and certain proteins. C6-NBD ceramide is a fluorescent probe taken up by cells and converted to C6-NBD sphingomyelin. Thus it may be used to monitor the biosynthesis and degradation of …
Kumar et al. and Zijlmans et al. have published in Nature Cell Biology that Polycomb repressive complex 2 (PRC2) epigenetically reduces lineage potential of hESCs. They utilized PRC2 inhibitors UNC1999 and EPZ-6438 (Tazemetostat) to examine the pathways involved.
JTE-607, a cell-permeable prodrug which is converted to its active COOH form via intracellular esterases, was originally found to inhibit cytokine release but its mechanism of action was unknown. More recently it was shown to inhibit pre-mRNA processing via inhibition of the endonuclease Cleavage and Polyadenylation Specificity Factor 3 (CPSF3), preventing the release of newly …
A team headed by distinguished neuroscientist Alcino Silva recently showed that expression of C-C chemokine receptor type 5 (CCR5) expression reduced memory recall, and maraviroc (Focus Cat.# 10-4260), a CCR5 antagonist, improved memory in ageing mice. Maraviroc is an FDA approved AIDS therapeutic with the potential to be repurposed for use in early memory loss.
Perylenequinones are a family of structurally novel fungal or plant natural products which act as photosensitizers. They absorb light energy, enabling them to generate reactive oxygen species (ROS) which can damage host cells. Two examples from this family are cercosporin and hypericin and many others have been identified.
In Nature Communications, Zhang et al. show that DJ001, a selective allosteric inhibitor of protein tyrosine phosphatase sigma (PTPĪ), promotes hematopoietic stem cell (HSC) regeneration. Treatment of irradiated human HSCs with DJ001 promoted the regeneration of HSCs capable of multilineage in vivo repopulation. For a comprehensive portfolio of small molecule stem cell effectors visit https://focusbiomolecules.com/stem-cells-main/.