World Drug database

II. Products Summary Daylight provides chemoinformatics tools and databases for life sciences. Daylight s product portfolio includes DayCart, THOR database, Merlin exploratory data analysis, ACD database, MedChem database, SPRESI database, WOMBAT database, World Drug Index database. 

Probably the most widely adopted and well-known method for estimating the likelihood of a compound (drug) being well absorbed is the rule-of-5 described by Lipinski and co-workers [1]. In analyzing 2245 compounds from the World Drug Index (WDI) database that were either considered for, or entered into, Phase II clinical trials, these authors developed the following rules ... 

WDI, the Derwent World Drug Index, is available from Derwent Publications Ltd., http //thomsonderwent.com/products/ Ir/wdi/ and from Daylight Chemical Information Systems, http //www.daylight.com/ products/databases /W DI. html. 

Most prediction tools for druglikeness use the MDL Available Chemicals Directory (ACD) [89] as a list of nondrugs and one of three databases as a list of drugs MDL Drug Data Report (MDDR) [89], MDL Comprehensive Medicinal Chemistry (CMC) [89], or Derwent World Drug Index (WDI) [90]. 

Similar analyses could be done for the movement of cocaine from Colombia to Europe, or the movement of heroin via the Balkan route, or any of a number of other trafficking patterns. The key limitation is the lack of standardised data. UNODC needs greater input from Member States to its individual seizures database, including detailed information on the nationalities of traffickers and the techniques employed. On this basis, important analysis of the world drug trafficking situation could be completed for the benefit of all. 

Veber DF, Johnson SR, Cheng HY et al. (2002) Molecular properties that influence the oral bioavailability of drug candidates. J Med Chem 45 2615-2623 World Drug Index Database WDI97, Derwent Publications Ltd., distributed by Daylight Chemical Information Systems, Inc... 

The failure of drugs at later stages of development, particularly in clinical trials, is very expensive for drug developers and, more importantly, patients. To better understand the key reasons for these failures, Lipinski et al,14 undertook an analysis of the properties of compounds that entered Phase II human clinical trials. They selected a subset of 2245 compounds from the World Drug Index (WDI) database of over 50000 compounds after eliminating the majority of compounds for various well-reasoned criteria. This subset of compounds had assigned trade names and, as a result, were assumed to have entered Phase II oral efficacy studies and be expected to have superior physico-chemical properties since they would have passed most of the other earlier clinical trial hurdles. 

In 2001, Lee and Schneider17 compared the properties of trade drugs (taken from the Derwent World Drug Index, WDI, n=5151) and natural products (taken from the BioScreenNP database, n= 10 495). These investigators described the comparison of parameters applicable only to the rule of five (molecular weight, log P, number of H donors per molecule, number of N per molecule, number of O per molecule and percentage of rule of five alerts). 

Barreca et al screened for non-nucleoside reverse transcriptase inhibitors of HIV-1 by searching the Derwent World Drug Index (WDI) and the Chemicals Available for Purchase (CAP) databases with a Catalyst model generated by LigandScout. A Fit value cutoff of 3.0 and Lipinski filters, followed by docking, led to the selection of three compounds, two of which were commercially available. A search for available close analogues of all three compounds finally led to the purchase of six compounds, of which five were shown to be active. 

From an analysis ofthe key properties of compounds in the World Drug Index (WDI), the now well-accepted rule-of-5 has been derived [136, 137]. It was concluded that compounds are most likely to have poor absorption when the molecular weight is more than 500, the calculated octanol/water partition coefficient (Clog P) is more than 5, number of H -bond donors is more than 5, and the number of H-bond acceptors is more than 10. Computation of these properties is now available as a simple but efficient ADME screen in commercial software. The rule-of-5 should be seen as a qualitative absorption/permeability predictor [138], rather than a quantitative predictor [139]. The rule-of-5 is not predictive for bioavailability as sometimes mistakenly assumed. An important factor for bioavailability in addition to absorption is liver first-pass effect (metabolism). The property distribution in drug-related chemical databases has been studied as another approach to understand drug-likeness [140,141]. 

World Drug Index, 2007. Database is available from Thomson Scientific at http //scientific.thomson.com/products/wdi/. 

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