Novel JAK Inhibitors to Reduce Graft-Versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation in a Preclinical Mouse Model.

Allogeneic hematopoietic cell transplantation (allo-HCT) is a highly effective, well-established treatment for patients with various hematologic malignancies and non-malignant diseases. The therapeutic benefits of allo-HCT are mediated by alloreactive T cells in donor grafts. However, there is a significant risk of graft-versus-host disease (GvHD), in which the donor T cells recognize recipient cells as foreign and attack healthy organs in addition to malignancies.

Identification of 4-Amino-Thieno[2,3-]Pyrimidines as QcrB Inhibitors in Mycobacterium tuberculosis.

Antibiotic resistance is a global crisis that threatens our ability to treat bacterial infections, such as tuberculosis, caused by Of the 10 million cases of tuberculosis in 2017, approximately 19% of new cases and 43% of previously treated cases were caused by strains of resistant to at least one frontline antibiotic. There is a clear need for new therapies that target these genetically resistant strains. Here, we report the discovery of a new series of antimycobacterial compounds, 4-amino-thieno[2,3-]pyrimidines, that potently inhibit the growth of To elucidate the mechanism by which these compounds inhibit , we selected for mutants resistant to a representative 4-amino-thieno[2,3-]pyrimidine and sequenced these strains to identify the mutations that confer resistance.

Evaluation of spiropiperidine hydantoins as a novel class of antimalarial agents.

Given the rise of parasite resistance to all currently used antimalarial drugs, the identification of novel chemotypes with unique mechanisms of action is of paramount importance. Since Plasmodium expresses a number of aspartic proteases necessary for its survival, we have mined antimalarial datasets for drug-like aspartic protease inhibitors. This effort led to the identification of spiropiperidine hydantoins, bearing similarity to known inhibitors of the human aspartic protease β-secretase (BACE), as new leads for antimalarial drug discovery.

Leaching of indaziflam applied at two rates under different rainfall situations in Florida Candler soil.

Indaziflam {N-[(1R, 2S)-2,3-dihydro-2,6-dimethyl-1H-inden-1-yl]-6-[(1RS)-1fluoroethyl]-1,3,5-triazine-2,4-diamine} is a new pre-emergence herbicide recently registered for a broad spectrum weed control in Florida citrus. Experiments were conducted to evaluate leaching of indaziflam applied at 73 and 145 g ai ha(-1) in Florida Candler soil under simulated rainfall of 5, 10, and 15 cm ha(-1). Indaziflam leached the least (12.

Controlling the intracellular localization of fluorescent polyamide analogues in cultured cells.

The intracellular distribution of fluorescent-labeled polyamides was examined in live cells. We showed that BODIPY-labeled polyamides accumulate in acidic vesicles, mainly lysosomes, in the cytoplasm of HCT116 colon cancer cells and human rheumatoid synovial fibroblasts (RSF). Verapamil blocked vesicular accumulation and led to nuclear accumulation of the BODIPY-labeled polyamide in RSFs.

Diastereoselectivity in the Epoxidation of Substituted Cyclohexenes by Dimethyldioxirane(1)(,)(2).

Three series of compounds based on the cyclohexene framework have been epoxidized by dimethyldioxirane. A pronounced dependence of epoxide diastereoselectivity on substituent has been observed. In addition there is a solvent influence on this stereoselectivity.