Data-driven medicinal chemistry in the era of big data.

Science, and the way we undertake research, is changing. The increasing rate of data generation across all scientific disciplines is providing incredible opportunities for data-driven research, with the potential to transform our current practices. The exploitation of so-called 'big data' will enable us to undertake research projects never previously possible but should also stimulate a re-evaluation of all our data practices.

Prednisolone induces the Wnt signalling pathway in 3T3-L1 adipocytes.

Synthetic glucocorticoids are potent anti-inflammatory drugs but show dose-dependent metabolic side effects such as the development of insulin resistance and obesity. The precise mechanisms involved in these glucocorticoid-induced side effects, and especially the participation of adipose tissue in this are not completely understood. We used a combination of transcriptomics, antibody arrays and bioinformatics approaches to characterize prednisolone-induced alterations in gene expression and adipokine secretion, which could underlie metabolic dysfunction in 3T3-L1 adipocytes.

Identification of new biomarker candidates for glucocorticoid induced insulin resistance using literature mining.

Background: Glucocorticoids are potent anti-inflammatory agents used for the treatment of diseases such as rheumatoid arthritis, asthma, inflammatory bowel disease and psoriasis. Unfortunately, usage is limited because of metabolic side-effects, e.g.

Org 214007-0: a novel non-steroidal selective glucocorticoid receptor modulator with full anti-inflammatory properties and improved therapeutic index.

Glucocorticoids (GCs) such as prednisolone are potent immunosuppressive drugs but suffer from severe adverse effects, including the induction of insulin resistance. Therefore, development of so-called Selective Glucocorticoid Receptor Modulators (SGRM) is highly desirable. Here we describe a non-steroidal Glucocorticoid Receptor (GR)-selective compound (Org 214007-0) with a binding affinity to GR similar to that of prednisolone.

X-ray structure of p38α bound to TAK-715: comparison with three classic inhibitors.

The p38α mitogen-activated protein kinase regulates the synthesis of pro-inflammatory cytokines in response to stimulation by a diverse set of stress signals. Various different chemotypes and clinical candidates that inhibit p38α function have been reported over the years. In this publication, the novel structure of p38α cocrystallized with the clinical candidate TAK-715 is reported.