Mood disorders

Alterations in 5-HT1B receptor function by p11 in depression-like states. Svenningsson, P. et al. Science 311, 77?80 (2006)

Although we know that the 5-hydroxytryptamine (5-HT) receptor family mediates the effects of antidepressant drugs, little is known about the role of individual receptors in the aetiology of depression. Svenningsson et al. used a yeast-two-hybrid screen to identify binding partners of the 5-HT receptor family and found that p11, an S100 EF-hand protein, specifically interacts with the 5-HT1B receptor. They also found that p11 is upregulated by antidepressant treatment and is involved in translocation of the 5-HT1B receptor to the cell surface. Correspondingly, p11-null mice had a lower number of 5-HT1B receptors and showed a depressive-like phenotype, suggesting that p11 has a key role in behavioural disorders.

Informatics

DrugBank: a comprehensive resource for in silico drug discovery and exploration. Wishart, D. S. et al. Nucleic Acids Res. 34, D668?D672 (2006)

Wishart and colleagues describe DrugBank ? a free, fully searchable database that combines chemical information for >4,100 drug entities with structural and sequence information for >14,000 drug targets. DrugBank has four major categories ? FDA-approved small-molecule drugs; FDA-approved biopharmaceuticals; nutraceuticals or micronutrients; and experimental drugs ? and has more than 80 data fields for each DrugCard entry. Researchers can search by text, sequence or structure, and can browse or use the 'pharmabrowse' function, which clusters drugs according to class or indication.

Structure-based drug design

Crystal structure of human T cell leukemia virus protease, a novel target for anticancer drug design. Li, M. et al. Proc. Natl Acad. Sci. USA 102, 18332?18337 (2005)

Li et al. report the structure of the human T-cell leukaemia virus-1 protease (HTLV-1 PR) bound to a substrate-based inhibitor. Although the overall protein fold is similar to other proteases, the authors found some structural differences that could have functional relevance. In particular, they identified key residues responsible for the resistance of HTLV-1 PR to anti-HIV drugs, which could be important in the rational design of novel antileukaemic drugs.

Cancer

Digitoxin inhibits the growth of cancer cell lines at concentrations commonly found in cardiac patients. Lopez-Lozaro, M. et al. J. Nat. Prod. 68, 1642?1645 (2005)

There have been several observations that the cardiac drug digitoxin also has anticancer effects. In this study, digitoxin and related compounds were screened against several cancer cell lines. In all four cell lines the IC50 value for growth inhibition for digitoxin and digoxin were within or below the concentration range used in cardiac patients, and digitoxin was particularly potent against a kidney cancer cell line renowned for its resistance to chemotherapy. Digitoxin's desirable pharmacological profile might therefore warrant its further investigation as a drug to treat kidney tumours and other cancers.