Topic
Druglikeness
About: Druglikeness is a research topic. Over the lifetime, 131 publications have been published within this topic receiving 2282 citations.
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TL;DR: Based on six physicochemical properties commonly used by medicinal chemists, the CNS MPO function may be used prospectively at the design stage to accelerate the identification of compounds with increased probability of success.
Abstract: The interplay among commonly used physicochemical properties in drug design was examined and utilized to create a prospective design tool focused on the alignment of key druglike attributes. Using a set of six physicochemical parameters ((a) lipophilicity, calculated partition coefficient (ClogP); (b) calculated distribution coefficient at pH = 7.4 (ClogD); (c) molecular weight (MW); (d) topological polar surface area (TPSA); (e) number of hydrogen bond donors (HBD); (f) most basic center (pKa)), a druglikeness central nervous system multiparameter optimization (CNS MPO) algorithm was built and applied to a set of marketed CNS drugs (N = 119) and Pfizer CNS candidates (N = 108), as well as to a large diversity set of Pfizer proprietary compounds (N = 11 303). The novel CNS MPO algorithm showed that 74% of marketed CNS drugs displayed a high CNS MPO score (MPO desirability score ≥ 4, using a scale of 0−6), in comparison to 60% of the Pfizer CNS candidates. This analysis suggests that this algorithm could p...
713 citations
TL;DR: Biochemical assays have largely supplanted functional biological assays as drug screening tools in the early stages of drug discovery and the physiochemical properties of leadlikeness and the surprising differences between those properties and the now classical definitions of druglikeness are becoming apparent.
353 citations
TL;DR: A survey of protein–protein interactions that have been identified as potential oncology targets and evaluates their attractiveness in terms of drug discovery focuses primarily on the structural characteristics of the participating binding sites, particularly the dimensions of the sites.
Abstract: An increasing number of protein-protein interactions have been identified as potential intervention points for the development of anticancer agents. However, such systems have historically been considered high-risk targets due to the relatively large interaction surfaces involved in protein-protein binding. This characterization has to be reexamined as progress has been made recently in identifying small-molecule inhibitors of several protein-protein systems in oncology including the p53-MDM2 interaction. This review presents a survey of protein-protein interactions that have been identified as potential oncology targets and evaluates their attractiveness in terms of drug discovery. The analysis focuses primarily on the structural characteristics of the participating binding sites, particularly the dimensions of the sites. Known ligands are also examined, especially with regard to their druglikeness.
148 citations
TL;DR: The synthesis, in vitro biological evaluation, and the SAR results of 1H-pyrazolo[3,4-b]pyridine derivatives, a new antichagasic agent series, show that trypanocidal activity observed depends on both geometric and stereoelectronic parameters.
75 citations
TL;DR: The in vitro anticancer evaluation revealed that compounds 2a and 4-6(a) exhibited increased potency towards CNS SNB-75 and Renal UO-31 cancer cell lines and strong to considerable correlations with rapamycin (mTOR inhibitor).
71 citations