Applying Molecular Modeling to the Design of Innovative, Non-Symmetrical CXCR4 Inhibitors with Potent Anticancer Activity.

The identification of new compounds with potential activity against CXC chemokine receptor type 4 (CXCR4) has been broadly studied, implying several chemical families, particularly AMD3100 derivatives. Molecular modeling has played a pivotal role in the identification of new active compounds. But, has its golden age ended? A virtual library of 450,000 tetraamines of general structure was constructed by using five spacers and 300 diamines, which were obtained from the corresponding commercially available cyclic amines.

Exploring the unexplored chemical space: Rational identification of new Tafenoquine analogs with antimalarial properties.

Patents tend to define a huge chemical space described by the combinatorial nature of Markush structures. However, the optimization of new principal active ingredient is frequently driven by a simple Free Wilson approach. This procedure leads to a highly focused study on the chemical space near a hit compound leaving many unexplored regions that may present highly biological active reservoirs.

Regulation of miRNA expression by α4β1 integrin-dependent multiple myeloma cell adhesion.

The α4β1 integrin regulates the trafficking of multiple myeloma (MM) cells and contributes to MM disease progression. MicroRNAs (miRNAs) can have both tumor suppressor and oncogenic roles and thus are key controllers of tumor evolution, and have been associated with different phases of MM pathogenesis. Using small RNAseq analysis, we show here that α4β1-dependent MM cell adhesion regulates the expression of forty different miRNAs, therefore expanding our current view of the α4β1 involvement in MM cell biology.

The big data era: The usefulness of folksonomy for natural language processing.

Background: A huge amount of clinical data is generated daily and it is usually filed in clinical reports as natural language. Data extraction and further analysis requires reading and manual review of each report, which is a time consuming process. With the aim to test folksonomy to quickly obtain and analyze the information contained in media reports we set up this study.

Cognate RNA-Binding Modes by the Alternative-Splicing Regulator MBNL1 Inferred from Molecular Dynamics.

The muscleblind-like protein family (MBNL) plays a prominent role in the regulation of alternative splicing. Consequently, the loss of MBNL function resulting from sequestration by RNA hairpins triggers the development of a neuromuscular disease called myotonic dystrophy (DM). Despite the sequence and structural similarities between the four zinc-finger domains that form MBNL1, recent studies have revealed that the four binding domains have differentiated splicing activity.