Ligand-based drug design

In general, the first step in virtual screening is the filtering by the application of Lipinski s Rule of Five [20]. Lipinski s work was based on the results of profiling the calculated physical property data in a set of 2245 compounds chosen from the World Drug Index. Polymers, peptides, quaternary ammonium, and phosphates were removed from this data set. Statistical analysis of this data set showed that approximately 90% of the remaining compounds had  

The cutoff values of this Rtile of Five the thresholds are a multiple of five) differ slightly within the pharmaceutical industry. Sometimes the Rule of Five is extended by a fifth condition  

Other filters used for prefiltering account for lead- [22, 23] or drug-likeness [24-26], an appropriate ADMET profile [27-30], or favorable properties concerning receptor binding [31, 32]. 

Historically, drug absorption, distribution, metabolism, excretion, and toxicity ADMET) studies in animal models were performed after the identification of a lead compound. In order to avoid costs, nowadays pharmaceutical companies evaluate the ADMET profiles of potential leads at an earlier stage of the development 

Concerning the distribution of a drug, models have been published for log BB blood/brain partition coefficient) for CNS-active drugs (CNS, central nervous system) crossing the blood-brain barrier (BBB) [38-45] and binding to human serum albumin (HSA) [46]. 

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Distinguishing Molecules of Different Biol< ical Activities and Finding a New Lead Structure - An Example of Ligand-Based Drug Design... 

In ligand-based drug design it is not necessary to know the structure of the receptor, or even the location of the binding site, although the conformationof the ligand bound to the recep-... 

D-Pharmacophore Identification for K-Opioid Agonists Using Ligand-Based Drug-Design Techniques... 

V Examples for ligand-based drug design A Lead optimization from the analysis of HTS data of a combinatorial library 138... 

Aparoy, P., K. K. Reddy et al. 2012. Structure and ligand based drug design strategies in the development of novel 5- LOX inhibitors. 19(22) 3763-3778. 

Ludi Ludi [17] is a product of Acceliys (Insight II) which can be used in both stmc-ture-based dmg design (protein structure is known) and ligand-based drug design (protein stmcture is not known). Based on this, it mns in two modes receptor mode and active analog mode. This mainly follows the fragment approach where initially... 

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