Prediction of Blood-Βrain Partitioning and Human Serum Albumin Binding Based on COSMO-RS σ-Moments
Models for the prediction of blood-brain partitioning (logBB) and human serum albumin binding (logK(HSA)) of neutral molecules were developed using the set of 5 COSMO-RS σ-moments as descriptors. These σ-moments have already been introduced earlier as a general descriptor set for partition coefficie...
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Published in | Journal of chemical information and modeling Vol. 47; no. 1; pp. 228 - 233 |
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Format | Journal Article |
Language | English |
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American Chemical Society
22.01.2007
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Abstract | Models for the prediction of blood-brain partitioning (logBB) and human serum albumin binding (logK(HSA)) of neutral molecules were developed using the set of 5 COSMO-RS σ-moments as descriptors. These σ-moments have already been introduced earlier as a general descriptor set for partition coefficients. They are obtained from quantum chemical calculations using the continuum solvation model COSMO and a subsequent statistical decomposition of the resulting polarization charge densities. The model for blood-brain partitioning was built on a data set of 103 compounds and yielded a correlation coefficient of r 2 = 0.71 and an rms error of 0.40 log units. The human serum albumin binding model was built on a data set of 92 compounds and achieved an r 2 of 0.67 and an rms error of 0.33 log units. Both models were validated by leave-one-out cross-validation tests, which resulted in q 2 = 0.68 and a qms error of 0.42 for the logBB model and in q 2 = 0.63 and a qms error of 0.35 for the logK(HSA) model. Together with the previously published models for intestinal absorption and for drug solubility the presented two models complete the COSMO-RS based set of ADME prediction models. |
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AbstractList | Models for the prediction of blood-brain partitioning (logBB) and human serum albumin binding (logK(HSA)) of neutral molecules were developed using the set of 5 COSMO-RS σ-moments as descriptors. These σ-moments have already been introduced earlier as a general descriptor set for partition coefficients. They are obtained from quantum chemical calculations using the continuum solvation model COSMO and a subsequent statistical decomposition of the resulting polarization charge densities. The model for blood-brain partitioning was built on a data set of 103 compounds and yielded a correlation coefficient of r 2 = 0.71 and an rms error of 0.40 log units. The human serum albumin binding model was built on a data set of 92 compounds and achieved an r 2 of 0.67 and an rms error of 0.33 log units. Both models were validated by leave-one-out cross-validation tests, which resulted in q 2 = 0.68 and a qms error of 0.42 for the logBB model and in q 2 = 0.63 and a qms error of 0.35 for the logK(HSA) model. Together with the previously published models for intestinal absorption and for drug solubility the presented two models complete the COSMO-RS based set of ADME prediction models. |
Author | Klamt, Andreas Diedenhofen, Michael Wichmann, Karin |
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Cites_doi | 10.1002/etc.5620211206 10.1002/aic.690481023 10.1021/j100007a062 10.1023/A:1012240703377 10.1016/0009-2614(89)85118-8 10.1021/jm010960b 10.1016/S1359-6446(03)02827-7 10.1021/ci000043z 10.1002/aic.690480518 10.1023/A:1011111506388 10.1021/jm049227l 10.1021/cr00023a012 10.1021/ci0501948 10.1021/ci049653f 10.1016/S0378-3812(00)00357-5 10.1021/jp980017s 10.1021/jm000942e 10.1023/A:1027359714663 10.1021/ci025530o |
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References | Hutter M. C (ci600385wb00008/ci600385wb00008_1) 2003; 17 Aureli L. (ci600385wb00005/ci600385wb00005_1) 2005; 48 Colmenarejo G. (ci600385wb00009/ci600385wb00009_1) 2001; 44 Klamt A. (ci600385wb00024/ci600385wb00024_1) 2002; 48 Klamt A. (ci600385wb00015/ci600385wb00015_1) 1998; 102 Keserü G. M. (ci600385wb00003/ci600385wb00003_1) 2001; 41 Klamt A. (ci600385wb00014/ci600385wb00014_1) 1998; 2 Klamt A. (ci600385wb00012/ci600385wb00012_1) 1993; 2 Rose K. (ci600385wb00006/ci600385wb00006_1) 2003 Kaznessis Y. N. (ci600385wb00001/ci600385wb00001_1) 2001; 15 Kier L. B. (ci600385wb00007/ci600385wb00007_1) 2002 ci600385wb00017/ci600385wb00017_1 Zissimos A. M. (ci600385wb00020/ci600385wb00020_1) 2002; 42 Otherm (ci600385wb00027/ci600385wb00027_1) 2004 Ertl P. (ci600385wb00002/ci600385wb00002_1) 2000; 43 Jones R. (ci600385wb00011/ci600385wb00011_1) 2005; 45 Klamt A. (ci600385wb00019/ci600385wb00019_1) 2002; 21 Sadowski J. (ci600385wb00022/ci600385wb00022_1) 1993; 93 Ahlrichs R. (ci600385wb00026/ci600385wb00026_1) 1989; 162 Ooms F. (ci600385wb00004/ci600385wb00004_1) 2002; 1587 Klamt A (ci600385wb00013/ci600385wb00013_1) 1995; 99 (ci600385wb00023/ci600385wb00023_1) 2002 Klamt A. (ci600385wb00016/ci600385wb00016_1) 2000; 172 Hornig M. (ci600385wb00029/ci600385wb00029_1) 2005; 45 Klamt A. (ci600385wb00010/ci600385wb00010_1) 2001; 15 Mehler C. (ci600385wb00018/ci600385wb00018_1) 2002; 48 Colmenarejo G. (ci600385wb00021/ci600385wb00021_1) 2001; 44 Clark D. E (ci600385wb00028/ci600385wb00028_1) 2003; 8 |
References_xml | – volume: 21 start-page: 2566 year: 2002 ident: ci600385wb00019/ci600385wb00019_1 publication-title: Environ. Toxicol. Chem. doi: 10.1002/etc.5620211206 contributor: fullname: Klamt A. – volume: 1587 start-page: 125 year: 2002 ident: ci600385wb00004/ci600385wb00004_1 publication-title: Biochim. Biophys. Acta contributor: fullname: Ooms F. – volume-title: Modeling Blood-Brain Barrier Partitioning Using Topological Structure Descriptors year: 2003 ident: ci600385wb00006/ci600385wb00006_1 contributor: fullname: Rose K. – volume: 48 start-page: 385 year: 2002 ident: ci600385wb00024/ci600385wb00024_1 publication-title: AIChE J. doi: 10.1002/aic.690481023 contributor: fullname: Klamt A. – volume: 99 start-page: 2235 year: 1995 ident: ci600385wb00013/ci600385wb00013_1 publication-title: J. Phys. Chem. doi: 10.1021/j100007a062 contributor: fullname: Klamt A – volume: 15 start-page: 708 year: 2001 ident: ci600385wb00001/ci600385wb00001_1 publication-title: J. Comput.-Aided Mol. Des. doi: 10.1023/A:1012240703377 contributor: fullname: Kaznessis Y. N. – volume: 162 start-page: 169 year: 1989 ident: ci600385wb00026/ci600385wb00026_1 publication-title: Chem. Phys. Lett. doi: 10.1016/0009-2614(89)85118-8 contributor: fullname: Ahlrichs R. – volume: 44 start-page: 4378 year: 2001 ident: ci600385wb00021/ci600385wb00021_1 publication-title: J. Med. Chem. doi: 10.1021/jm010960b contributor: fullname: Colmenarejo G. – volume-title: QSAR Modeling of Drug Binding to Protein. β-Lactam Serum Binding and Albumin Binding Affinity year: 2002 ident: ci600385wb00007/ci600385wb00007_1 contributor: fullname: Kier L. B. – volume: 8 start-page: 933 year: 2003 ident: ci600385wb00028/ci600385wb00028_1 publication-title: Drug Discovery Today doi: 10.1016/S1359-6446(03)02827-7 contributor: fullname: Clark D. E – volume: 41 start-page: 128 year: 2001 ident: ci600385wb00003/ci600385wb00003_1 publication-title: J. Chem. Inf. Comput. Sci. doi: 10.1021/ci000043z contributor: fullname: Keserü G. M. – volume: 48 start-page: 1099 year: 2002 ident: ci600385wb00018/ci600385wb00018_1 publication-title: AICHE J. doi: 10.1002/aic.690480518 contributor: fullname: Mehler C. – volume: 15 start-page: 365 year: 2001 ident: ci600385wb00010/ci600385wb00010_1 publication-title: J. Comput.-Aided Mol. Des. doi: 10.1023/A:1011111506388 contributor: fullname: Klamt A. – volume: 48 start-page: 2479 year: 2005 ident: ci600385wb00005/ci600385wb00005_1 publication-title: J. Med. Chem. doi: 10.1021/jm049227l contributor: fullname: Aureli L. – volume: 93 start-page: 2581 year: 1993 ident: ci600385wb00022/ci600385wb00022_1 publication-title: Chem. Rev. doi: 10.1021/cr00023a012 contributor: fullname: Sadowski J. – volume: 45 start-page: 1177 year: 2005 ident: ci600385wb00029/ci600385wb00029_1 publication-title: J. Chem. Inf. Model. doi: 10.1021/ci0501948 contributor: fullname: Hornig M. – volume-title: version C2.0 release 01.04 year: 2004 ident: ci600385wb00027/ci600385wb00027_1 contributor: fullname: Otherm – volume: 45 start-page: 1342 year: 2005 ident: ci600385wb00011/ci600385wb00011_1 publication-title: J. Chem. Inf. Model. doi: 10.1021/ci049653f contributor: fullname: Jones R. – volume: 172 start-page: 72 year: 2000 ident: ci600385wb00016/ci600385wb00016_1 publication-title: Fluid Phase Equilib. doi: 10.1016/S0378-3812(00)00357-5 contributor: fullname: Klamt A. – ident: ci600385wb00017/ci600385wb00017_1 – volume: 102 start-page: 5085 year: 1998 ident: ci600385wb00015/ci600385wb00015_1 publication-title: J. Phys. Chem. A doi: 10.1021/jp980017s contributor: fullname: Klamt A. – volume: 43 start-page: 3717 year: 2000 ident: ci600385wb00002/ci600385wb00002_1 publication-title: J. Med. Chem. doi: 10.1021/jm000942e contributor: fullname: Ertl P. – volume: 17 start-page: 433 year: 2003 ident: ci600385wb00008/ci600385wb00008_1 publication-title: J. Comput.-Aided Mol. Des. doi: 10.1023/A:1027359714663 contributor: fullname: Hutter M. C – volume: 44 start-page: 4378 year: 2001 ident: ci600385wb00009/ci600385wb00009_1 publication-title: J. Med. Chem. doi: 10.1021/jm010960b contributor: fullname: Colmenarejo G. – volume-title: MOPAC 2002 year: 2002 ident: ci600385wb00023/ci600385wb00023_1 – volume: 42 start-page: 1331 year: 2002 ident: ci600385wb00020/ci600385wb00020_1 publication-title: J. Chem. Inf. Comput. Sci. doi: 10.1021/ci025530o contributor: fullname: Zissimos A. M. – volume: 2 start-page: 615 volume-title: Encyclopedia of Computational Chemistry year: 1998 ident: ci600385wb00014/ci600385wb00014_1 contributor: fullname: Klamt A. – volume: 2 start-page: 805 year: 1993 ident: ci600385wb00012/ci600385wb00012_1 publication-title: J. Chem. Soc., Perkin Trans. contributor: fullname: Klamt A. |
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Title | Prediction of Blood-Βrain Partitioning and Human Serum Albumin Binding Based on COSMO-RS σ-Moments |
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