Databases drug-likeness

Applying this procedure to investigation of the metabolic stability of CYP2D6, we were able to find a model to correctly classify metabolically stable and unstable compounds. This model was trained using a set of 129 compounds from the Bio-Print [31] database. Drug-likeness and solubility properties were used as primary filter in order to eliminate unattractive compounds and all those compounds classified as not soluble, which are always classified as metabolically stable. The data-... 

From an analysis of the key properties of compounds in the World Dmg Index the now well accepted Rule-of-5 has been derived [25, 26]. It was concluded that compounds are most Hkely to have poor absorption when MW>500, calculated octanol-water partition coefficient Clog P>5, number of H-bond donors >5 and number of H-bond acceptors >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/permeabiHty predictor [43], rather than a quantitative predictor [140]. The Rule-of-5 is not predictive for bioavail-abihty as sometimes mistakenly is assumed. An important factor for bioavailabihty in addition to absorption is liver first-pass effect (metaboHsm). The property distribution in drug-related chemical databases has been studied as another approach to understand drug-likeness [141, 142]. 

Baurin, N., Baker, R., Richardson, C., Chen, I., Foloppe, N., Potter, A., Jordan, A., Roughley, S., Parratt, M., Greany, P., Morley, D., Hubbard, R. E. Drug-like annotation and duplicate analysis of a 23-supplier chemical database totalling 2.7 million compounds. J. Chem. Inf. 

The SHAPES Linking Library was designed to facilitate the use of combinatorial chemistry to follow up screening hits [11]. This library consists primarily of commercially available compounds containing two drug-like scaffolds connected by a linkage that is synthetically accessible. To construct this library, a database of commercially available compounds was filtered to select for drug-likeness and the presence of the desired molecular... 

SheridanRP. (2003) Finding multiactivity substructures by mining databases of drug-like compounds. /. Chem. Inf. Comput. Sci. 43 1037-1050. 

However, none of the above-mentioned databases are directly usable to generate a collection of druggable protein active sites customized to accommodate small molecular-weight drug-like ligands. Generally, no... 

Since for most COSMO-RS applications only the a-profile and some information about the area and volume of the molecule is needed, the basic idea of COSMO/rag is the composition of the CT-profile of new molecules from existing cr-profiles of the locally most similar molecules, whose u-profiles have already been precalculated and are stored in a database. For this purpose we have developed a database of 40,000 (as of February 2005) pre-calcu-lated COSMO files of smaller basic- and larger drug-like compounds, trying to maximize the diversity of the compounds represented in the database. 

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