| pubmed-article:12510879 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:12510879 | lifeskim:mentions | umls-concept:C0030360 | lld:lifeskim |
| pubmed-article:12510879 | lifeskim:mentions | umls-concept:C0085862 | lld:lifeskim |
| pubmed-article:12510879 | lifeskim:mentions | umls-concept:C1299583 | lld:lifeskim |
| pubmed-article:12510879 | lifeskim:mentions | umls-concept:C1332829 | lld:lifeskim |
| pubmed-article:12510879 | lifeskim:mentions | umls-concept:C0679932 | lld:lifeskim |
| pubmed-article:12510879 | lifeskim:mentions | umls-concept:C0936012 | lld:lifeskim |
| pubmed-article:12510879 | lifeskim:mentions | umls-concept:C0243077 | lld:lifeskim |
| pubmed-article:12510879 | lifeskim:mentions | umls-concept:C0392762 | lld:lifeskim |
| pubmed-article:12510879 | lifeskim:mentions | umls-concept:C0282354 | lld:lifeskim |
| pubmed-article:12510879 | lifeskim:mentions | umls-concept:C1608386 | lld:lifeskim |
| pubmed-article:12510879 | lifeskim:mentions | umls-concept:C1549571 | lld:lifeskim |
| pubmed-article:12510879 | lifeskim:mentions | umls-concept:C1706765 | lld:lifeskim |
| pubmed-article:12510879 | pubmed:issue | 7 | lld:pubmed |
| pubmed-article:12510879 | pubmed:dateCreated | 2003-1-3 | lld:pubmed |
| pubmed-article:12510879 | pubmed:abstractText | This study describes the use of alignment-independent descriptors for obtaining qualitative and quantitative predictions of the competitive inhibition of CYP2C9 on a serie of highly structurally diverse compounds. This was accomplished by calculating alignment independent descriptors in ALMOND. These GRid INdependent Descriptors (GRIND) represent the most important GRID-interactions as a function of the distance instead of the actual position of each grid-point. The experimental data was determined under uniform conditions. The inhibitor data set consists of 35 structurally diverse competitive stereospecific inhibitors of the cytochrome P450 2C9 and the non -inhibitor data set of 46 compounds. In a PLS discriminant analysis 21 inhibitors and 21 non-inhibitors (1 and 0 as activities) were analyzed using the ALMOND program obtaining a model with an r2 of 0.74 and a cross-validation value (q2) of 0.64. The model was externally validated with 39 compounds (14 inhibitors/25 non-inhibitors). 74% of the compounds were correctly predicted and an additional 13% was assigned to a borderline cluster. Thereafter, a model for quantitative predictions was generated by a PLS analysis of the GRIND descriptors using the experimental Ki-value for 21 of the competitive inhibitors (r2 = 0.77, q2 = 0.60). The model was externally validated using 12 compounds and predicted 11 out of 12 of the Ki-values within 0.5 log units. The discriminant model will be useful in screening for CYP2C9 inhibitors from large compound collections. The 3D-QSAR model will be used during lead optimization to avoid chemistry that result in inhibition of CYP2C9. | lld:pubmed |
| pubmed-article:12510879 | pubmed:language | eng | lld:pubmed |
| pubmed-article:12510879 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12510879 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:12510879 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12510879 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12510879 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12510879 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:12510879 | pubmed:month | Jul | lld:pubmed |
| pubmed-article:12510879 | pubmed:issn | 0920-654X | lld:pubmed |
| pubmed-article:12510879 | pubmed:author | pubmed-author:AnderssonTomm... | lld:pubmed |
| pubmed-article:12510879 | pubmed:author | pubmed-author:MasimirembwaC... | lld:pubmed |
| pubmed-article:12510879 | pubmed:author | pubmed-author:KarlénAndersA | lld:pubmed |
| pubmed-article:12510879 | pubmed:author | pubmed-author:ZamoraIsmaelI | lld:pubmed |
| pubmed-article:12510879 | pubmed:author | pubmed-author:AfzeliusLovis... | lld:pubmed |
| pubmed-article:12510879 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:12510879 | pubmed:volume | 16 | lld:pubmed |
| pubmed-article:12510879 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:12510879 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:12510879 | pubmed:pagination | 443-58 | lld:pubmed |
| pubmed-article:12510879 | pubmed:dateRevised | 2006-11-15 | lld:pubmed |
| pubmed-article:12510879 | pubmed:meshHeading | pubmed-meshheading:12510879... | lld:pubmed |
| pubmed-article:12510879 | pubmed:meshHeading | pubmed-meshheading:12510879... | lld:pubmed |
| pubmed-article:12510879 | pubmed:meshHeading | pubmed-meshheading:12510879... | lld:pubmed |
| pubmed-article:12510879 | pubmed:meshHeading | pubmed-meshheading:12510879... | lld:pubmed |
| pubmed-article:12510879 | pubmed:year | 2002 | lld:pubmed |
| pubmed-article:12510879 | pubmed:articleTitle | Discriminant and quantitative PLS analysis of competitive CYP2C9 inhibitors versus non-inhibitors using alignment independent GRIND descriptors. | lld:pubmed |
| pubmed-article:12510879 | pubmed:affiliation | Department of Organic Pharmaceutical Chemistry, Biomedical Center, Uppsala University, Uppsala, Sweden. Lovisa.Afzelius@astrazeneca.com | lld:pubmed |
| pubmed-article:12510879 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:12510879 | pubmed:publicationType | Comparative Study | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:12510879 | lld:pubmed |
