A refined 3-dimensional QSAR of cytochrome P450 2C9: computational predictions of drug interactions.
A refined 3-dimensional QSAR of cytochrome P450 2C9: computational predictions of drug interactions.
复制标题
细胞色素 P450 2C9 的精细 3 维 QSAR：药物相互作用的计算预测。
DOI：
10.1021/jm000048n
复制
发表时间：
2000
影响因子：
7.3
通讯作者：
Jones,JP
中科院分区：
文献类型：
--
作者：
Rao,S;Aoyama,R;Schrag,M;Trager,WF;Rettie,A;Jones,JP
本文报道了一个基于配体的模型，用于预测细胞色素P450 2C 9（CYP 2C 9）抑制剂的Ki值。该CoMFA模型用于预测不在训练集中的14种结构不同的化合物的亲和力，并且似乎是稳健的。预测的平均误差为6 μM。实验测得的14种化合物的Ki值范围为0.1 ~ 48 μM。留一法交叉验证偏最小二乘法给出了各种模型的aq 2值在0.6和0.8之间，这表明内部一致性。随机分配生物数据的结构导致负q2值。这些模型是有用的，因为它们建立了一个药效团结合CYP 2C 9，可以测试与定点诱变。这些模型也可用于筛选潜在的药物相互作用，并设计不会以高亲和力与这种酶结合的化合物。
A ligand-based model is reported that predicts theKivalues for cytochrome P450 2C9 (CYP2C9) inhibitors. This CoMFA model was used to predict the affinity of 14 structurally diverse compounds not in the training set and appears to be robust. The mean error of the predictions is 6 μM. The experimentally measuredKivalues of the 14 compounds range from 0.1 to 48 μM. Leave-one-out cross-validated partial least-squares gives aq2value of between 0.6 and 0.8 for the various models which indicates internal consistency. Random assignment of biological data to structure leads to negativeq2values. These models are useful in that they establish a pharmacophore for binding to CYP2C9 that can be tested with site-directed mutagenesis. These models can also be used to screen for potential drug interactions and to design compounds that will not bind to this enzyme with high affinity.