DrugBank 4.0: shedding new light on drug metabolism.

DrugBank (http://www.drugbank.ca) is a comprehensive online database containing extensive biochemical and pharmacological information about drugs, their mechanisms and their targets. Since it was first described in 2006, DrugBank has rapidly evolved, both in response to user requests and in response to changing trends in drug research and development. Previous versions of DrugBank have been widely used to facilitate drug and in silico drug target discovery. The latest update, DrugBank 4.0, has been further expanded to contain data on drug metabolism, absorption, distribution, metabolism, excretion and toxicity (ADMET) and other kinds of quantitative structure activity relationships (QSAR) information. These enhancements are intended to facilitate research in xenobiotic metabolism (both prediction and characterization), pharmacokinetics, pharmacodynamics and drug design/discovery. For this release, >1200 drug metabolites (including their structures, names, activity, abundance and other detailed data) have been added along with >1300 drug metabolism reactions (including metabolizing enzymes and reaction types) and dozens of drug metabolism pathways. Another 30 predicted or measured ADMET parameters have been added to each DrugCard, bringing the average number of quantitative ADMET values for Food and Drug Administration-approved drugs close to 40. Referential nuclear magnetic resonance and MS spectra have been added for almost 400 drugs as well as spectral and mass matching tools to facilitate compound identification. This expanded collection of drug information is complemented by a number of new or improved search tools, including one that provides a simple analyses of drug-target, -enzyme and -transporter associations to provide insight on drug-drug interactions.

CD158k/KIR3DL2 and NKp46 are frequently expressed in transformed mycosis fungoides.

Malignant Sezary cells express the natural killer (NK) receptors KIR3DL2 (CD158k) and Nkp46 and may co-express activating killer immunoglobulin-like receptors (KIR) that may participate to neoplastic T-cell activation through the JNK pathway. Little is known regarding NK receptor expression in other cutaneous T-cell lymphomas. We studied the expression of KIR and natural cytotoxicity receptor (NCR) transcripts, and KIR3DL1/2 at the protein level, in 16 skin biopsies from 10 patients with transformed mycosis fungoides (tMF). Some KIR and NCR transcripts were found in all cases, with various repertoires. Two to nine different KIR receptors were expressed in a single biopsy. Among them, KIR3DL2 was the most frequent, with the highest level of expression in quantitative analyses and correlated with in situ protein expression, while phosphorylated JNK was never detected. Among NCR, NKp46 was expressed in all investigated cases. The role of KIR3DL2 and NKp46 in tMF oncogenesis remains to be studied.