Cardiovascular diseases

First experience with direct factor Xa inhibition in patients with stable coronary disease. A pharmacokinetic and pharmacodynamic evaluationDyke, C. K. et al. Circulation 2002 Apr 29 (doi: 10.1161/01.CIR.0000016351.12759.52)

Inhibition of factor Xa — which has a key role in the formation of blood clots — might be more effective and safer than current treatments, such as heparin and warfarin, for preventing the formation of potentially life-threatening blood clots in patients with coronary artery disease. In this Phase Ib trial involving 73 patients, the small-molecule factor Xa inhibitor DX-9065a (Daiichi Pharmaceutical Company) was shown to be safe in patients with stable coronary disease who were receiving standard therapy (for example, aspirin, beta-blockers and statins), paving the way for larger clinical studies with this new drug class.

Computational chemistry

A virtual screening method for prediction of the hERG potassium channel liability of compound librariesRoche, O. et al. ChemBioChem 3, 455–459 (2002)

Compounds that block the hERG potassium channel cause QT prolongation, a disorder of cardiac-action-potential repolarization that can lead to potentially lethal cardiac arrhythmias. More than 70 common drugs have been shown to have this serious side effect. Using various techniques to find appropriate molecular descriptors, Roche et al. developed a virtual-screening method for predicting hERG affinity, which could classify known blockers and non-blockers with 71% and 93% accuracy, respectively.

Blood diseases

Treatment of hypereosinophilic syndrome with imatinib mesilateGleich, G. J. et al. Lancet 359, 1577–1578 (2002)

Hypereosinophilic syndrome (HES) is a potentially fatal blood disease that is characterized by an increase in inflammatory white blood cells, which results in organ damage. Drugs used in patients with chronic myelogenous leukemia (CML) have been used in HES, but with limited effect. Gleich et al. tested Gleevec (imatinib mesilate), the recently approved breakthrough treatment for CML, in five patients with HES, and four showed marked improvements; however, the underlying mechanism remains to be elucidated.

Genomics

Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2)Bentley, S. D. et al. Nature 417, 141–147 (2002)

Actinomycetes, such as Streptomyces coelicolor, produce two-thirds of the natural antibiotics in use, and also many anticancer agents. The genome sequence of S. coelicolor, the model actinomycete, should facilitate experiments aimed at manipulating the biosynthetic gene clusters of therapeutic natural products to produce novel agents with potentially improved activities.