ADME screens

Kesurn GM, Molnar L. METAPRINT a metabolic fingerprint. Application to cassette design for high-thronghpnt ADME screening. J Chem Inf Comput Sci 2002 42 437-44. 

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]. 

Saunders, K. Automation and robotics in ADME screening. Drug Discov. Today Technol. 2004, 1, 373-380. 

The advent of automation techniques moved high-throughput ADME screening from individual test tube to multiwell plates. The use of 96- and 384-well plates produced a data explosion and the need to capture, store, and mine data so that it can be used effectively. A database for storing and... 

Benzodiazepinones such as 4 [14] have been claimed as PDE2 inhibitors, as have oxindoles related to 5 [15]. Compound 5 was reported to have an IC50 of 40 nM against PDE2. Preliminary ADME screening showed 5 to have the physicochemical and pharmacokinetic characteristics that should allow use as a tool to study PDE2 function in more detail [16]. 

Comer, J. and Box, K., High throughput measurement of drug pK, values for ADME screening, JALA, 8, 55, 2003. 

LGMS APPLICATION IN HIGH-THROUGHPUT ADME SCREEN... 

With respect to compoimd management, the testing process, and assay and data validation, the BioPrint ADME assays are similar to the pharmacological assays. The test compounds are handled similarly with aliquots of prepared compounds set aside for the ADME screening. The only deviation... 

Sengupta, D., Verma, D., Naik, P.K. Docking-MM-GB/SA and ADME screening of HIV-1 NNRTI inhibitor nevirapine and its analogues. In Silico Biol. 2008, 8, 275-89. 

ADME screening Plasma, urine, CSF liver, brain, S9 fractions, microsomes, PAMPA 4.8 Herman, 2002a... 

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