Abstract:
:The human breast cancer resistance protein (BCRP), one of the members of the large ATP binding cassette (ABC) transporter superfamily, is crucial for resistance against chemotherapeutic agents. Currently, it has been emerged as one of the best biological targets for the designing of small molecule drugs capable of eliminating multidrug resistance in breast cancer. In order to gain insights into the relationship between the molecular structure of compounds and the ABCG2 inhibition, a multi-QSAR approach using different methods was performed on a dataset of 294 ABCG2 inhibitors with diverse scaffolds. The best models obtained by different chemometric methods have the following statistical characteristics: Monte Carlo Optimization-based QSAR (sensitivity = 0.905, specificity = 0.6255, accuracy = 0.756, and MCC = 0.545), Bayesian classification model (sensitivity = 0.735, specificity = 0.775, and concordance = 0.757); structural and physicochemical interpretation analysis-random forest method (balance accuracy = 0.750, sensitivity = 0.810, and specificity = 0.700). Additionally, structural fingerprints modulating the ABCG2 inhibitory properties were identified from the best models of each method and also validated with each other. The current modelling study is an attempt to get a deep insight into the different important structural fingerprints modulating ABCG2 inhibition.
journal_name
SAR QSAR Environ Resjournal_title
SAR and QSAR in environmental researchauthors
Ghosh K,Bhardwaj B,Amin SA,Jha T,Gayen Sdoi
10.1080/1062936X.2020.1771769subject
Has Abstractpub_date
2020-06-01 00:00:00pages
439-455issue
6eissn
1062-936Xissn
1029-046Xjournal_volume
31pub_type
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journal_title:SAR and QSAR in environmental research
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journal_title:SAR and QSAR in environmental research
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abstract::Juvenile hormone esterase (JHE) plays a key role in the development and metamorphosis of holometabolous insects. Its inhibitors could possibly be targeted for insect control. Conversely, JHE may also be involved in endocrine disruption by xenobiotics, resulting in detrimental effects in beneficial insects. There is th...
journal_title:SAR and QSAR in environmental research
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doi:10.1080/1062936X.2013.875061
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journal_title:SAR and QSAR in environmental research
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journal_title:SAR and QSAR in environmental research
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journal_title:SAR and QSAR in environmental research
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doi:10.1080/1062936X.2019.1615547
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abstract::The high-throughput screening (HTS) of large proprietary compound collections and combinatorial libraries has put an increased pressure on getting pharmacokinetic and drug metabolism data as early as possible. Properties related to absorption, distribution, metabolism and excretion (ADME) can be estimated by a range o...
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abstract::Strong sorption of hydrophobic organic contaminants to soot or black carbon (BC) is an important environmental process limiting the bioremediation potential of contaminated soils and sediments. Reliable methods to predict BC sorption coefficients for organic contaminants are therefore required. A computer simulation b...
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journal_title:SAR and QSAR in environmental research
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