A Novel NMR-Based Protocol to Screen Ultralow Molecular Weight Fragments.

Fragment-based lead discovery has emerged as one of the most efficient screening strategies for finding hit molecules in drug discovery. Recently, a novel strategy based on a class of fragments characterized by an ultralow molecular weight (ULMW) has been proposed. These fragments bind to the target with a very low affinity, requiring reliable biophysical methods for detection.

Design, synthesis and biological evaluation of novel 2,4-thiazolidinedione derivatives able to target the human BAG3 protein.

The Bcl-2-associated athanogene 3 (BAG3) protein plays multiple roles in controlling cellular homeostasis, and it has been reported to be deregulated in many cancers, leading tumor cell apoptosis escape. BAG3 protein is then an emerging target for its oncogenic activities in both leukemia and solid cancers, such as medulloblastoma. In this work a series of forty-four compounds were designed and successfully synthesized by the modification and optimization of a previously reported 2,4-thiazolidinedione derivative 28.

Drugging the Undruggable Monothiol Glutaredoxin 1.

Trypanosoma brucei is a species of kinetoplastid causing sleeping sickness in humans and nagana in cows and horses. One of the peculiarities of this species of parasites is represented by their redox metabolism. One of the proteins involved in this redox machinery is the monothiol glutaredoxin 1 (1CGrx1) which is characterized by a unique disordered N-terminal extension exclusively conserved in trypanosomatids and other organisms.

Small-Molecule Inhibitor of Flaviviral NS3-NS5 Interaction with Broad-Spectrum Activity and Efficacy .

Every year, dengue virus (DENV) causes one hundred million infections worldwide that can result in dengue disease and severe dengue. Two other mosquito-borne flaviviruses, i.e.