Development of reliable aqueous solubility models and their application   in druglike analysis

doi:10.1021/ci700096r

CORC > 北京大学 > 化学与分子工程学院

	Development of reliable aqueous solubility models and their application in druglike analysis
	Wang, Junmei ; Krudy, George ; Hou, Tingjun ; Zhang, Wei ; Holland, George ; Xu, Xiaojie
刊名	journal of chemical information and modeling
	2007
关键词	ORGANIC-COMPOUNDS STRUCTURE REPRESENTATION MOLECULAR-STRUCTURE ADME EVALUATION PREDICTION DISCOVERY
DOI	10.1021/ci700096r
英文摘要	In this work, two reliable aqueous solubility models, ASMS (aqueous solubility based on molecular surface) and ASMS-LOGP (aqueous solubility based on molecular surface using ClogP as a descriptor), were constructed by using atom type classified solvent accessible surface areas and several molecular descriptors for a diverse data set of 1708 molecules. For ASMS (without using ClogP as a descriptor), the leave-one-out q(2) and root-mean-square error (RMSE) were 0.872 and 0.748 log unit, respectively. ASMS-LOGP was slightly better than ASMS (q(2) = 0.886, RMSE = 0.705). Both models were extensively validated by three cross-validation tests and encouraging predictability was achieved. High throughput aqueous solubility prediction was conducted for a number of data sets extracted from several widely used databases. We found that real drugs are about 20-fold more soluble than the so-called druglike molecules in the ZINC database, which have no violation of Lipinski's "Rule of 5" at all. Specifically, oral drugs are about 16-fold more soluble, while injection drugs are 50-60-fold more soluble. If the criterion of a molecule to be soluble is set to -5 log unit, about 85% of real drugs are predicted as soluble; in contrast only 50% of druglike molecules in ZINC are soluble. We concluded that the two models could be served as a rule in druglike analysis and an efficient filter in prioritizing compound libraries prior to high throughput screenings (HTS).; Chemistry, Medicinal; Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; SCI(E); EI; 35; ARTICLE; 4; 1395-1404; 47
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/250200]
专题	化学与分子工程学院
推荐引用方式 GB/T 7714	Wang, Junmei,Krudy, George,Hou, Tingjun,et al. Development of reliable aqueous solubility models and their application in druglike analysis[J]. journal of chemical information and modeling,2007.
APA	Wang, Junmei,Krudy, George,Hou, Tingjun,Zhang, Wei,Holland, George,&Xu, Xiaojie.(2007).Development of reliable aqueous solubility models and their application in druglike analysis.journal of chemical information and modeling.
MLA	Wang, Junmei,et al."Development of reliable aqueous solubility models and their application in druglike analysis".journal of chemical information and modeling (2007).