Kinases

Reeves, M. P. et al. Disabling poxvirus pathogenesis by inhibition of Abl-family tyrosine kinases. Nature Med. (10.1038/nm1265)

Cell-associated enveloped virions (CEVs) rely on actin to be able to move from just outside the host-cell nucleus to the cell surface, where they fuse with the cell membrane, detach and move on to infect another cell. This study shows that the CEVs require Abl and Src-family tyrosine kinases for actin motility, and specifically Abl tyrosine kinase when detaching from the cell. The authors found that the Abl-family kinase inhibitor imatinib (Gleevec; Novartis) blocks the release of CEVs and reduced viral dissemination and improved survival of infected mice.

Infectious diseases

Ferreras, J. A. et al. Small-molecule inhibition of siderophore biosynthesis in Mycobacterium tuberculosis and Yersinia pestis. Nature Chem. Biol. (10.1038/nchembio706)

The causative agents of tuberculosis and plague, Mycobacterium tuberculosis and Yersinia pestis, respectively, both share a common method of pathogenicity. Both use 'siderophores' to chelate iron from the host with extremely high affinity. This paper reports the identification of a class of non-hydrolyzable acyl-AMP analogues that inhibit a crucial step in siderophore biosynthesis called domain salicylation. One particular inhibitor, salicyl-AMS, is a promising lead compound for the development of novel antibiotics against tuberculosis and plague.

Anticancer drugs

Dothager, R. S. et al. Synthesis and identification of small molecules that potently induce apoptosis in melanoma cells through G1 cell cycle arrest. J. Am. Chem. Soc. 127, 8686–8696 (2005)

The very features of melanocytes that protect cells against DNA damage in normal skin also protect against cell-cycle arrest caused by chemotherapy. To search for more effective melanoma therapies, the authors of this study synthesized a combinatorial library of potential pro-apoptotic compounds and identified a class of small molecules called triphenylmethylamides (TPMAs) that potently induce cell death in melanoma cell lines without causing death to normal bone-marrow cells.

Parkinson's disease

McCall, R. B. et al. Sumanirole, a highly dopamine D2 selective receptor agonist: in vitro and in vivo pharmacologic characterization and efficacy in animal models of Parkinson's disease. J. Pharm. Exp. Ther. (10.1124/jpet.105.084202)

The first dopamine D2-receptor-selective agonist has been reported and shows promise in animal models as a potential drug against Parkinson's disease. Sumanirole was shown in radioligand binding assays to have more than 200-fold more selectivity for the D2 receptor subtype than any other dopamine receptor subtype. The authors describe how sumanirole causes many physiological responses in animals that are attributable to D2-receptor activity, and improved disability scores and locomotor activities in rodent and primate models of Parkinson's disease.