Journal ArticleDOI
Comparative validated molecular modeling of p53-HDM2 inhibitors as antiproliferative agents.
Chanchal Mondal,Amit Kumar Halder,Nilanjan Adhikari,Achintya Saha,Krishna Das Saha,Shovanlal Gayen,Tarun Jha +6 more
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TLDR
Comparison molecular modeling techniques may help to design novel HDM2 inhibitors to understand structural and physicochemical requirements for higher activity and adjudging predictability as well as validation of different modeling techniques.About:
This article is published in European Journal of Medicinal Chemistry.The article was published on 2015-01-27. It has received 28 citations till now. The article focuses on the topics: Pharmacophore & LigandScout.read more
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Inhibitors of the MDM2-p53 protein-protein interaction based on an isoindolinone scaffold
Hardcastle,Ahmed,Barrett,Endicott,Golding,Griffin,Gruber,Hutton,Kemp,Lunec,Noble,Riedinger,Smyth +12 more
TL;DR: In this paper, a set of weakly potent lead compounds, using in silico screening and small library synthesis, has been identified as inhibitors of the MDM2-p53 interaction.
Journal ArticleDOI
Medicinal Chemistry Strategies to Disrupt the p53-MDM2/MDMX Interaction.
Agostinho Lemos,Mariana Leão,Joana Soares,Andreia Palmeira,Madalena Pinto,Lucília Saraiva,Maria Emília Sousa +6 more
TL;DR: The knowledge of structural requirements crucial to the development of small‐molecule inhibitors of the p53–MDM2/MDMX interactions has enabled the identification of novel antitumor agents with improved in vivo efficacy.
Journal ArticleDOI
Exploring pyrazolo[3,4-d]pyrimidine phosphodiesterase 1 (PDE1) inhibitors: a predictive approach combining comparative validated multiple molecular modelling techniques.
TL;DR: A number of pyrazolo[3,4-d]pyrimidine PDE1 inhibitors were subjected to different molecular modelling techniques to get a detailed knowledge about the physicochemical and structural requirements for higher inhibitory activity.
Journal ArticleDOI
First molecular modeling report on novel arylpyrimidine kynurenine monooxygenase inhibitors through multi-QSAR analysis against Huntington's disease: A proposal to chemists!
TL;DR: Fiftysix arylpyrimidine KMO inhibitors are structurally explored through regression and classification based multi-QSAR modeling, pharmacophore mapping and molecular docking approaches, and ten new compounds are proposed and validated through the modeling that may be effective in accelerating Huntington's disease drug discovery efforts.
Journal ArticleDOI
First report on the structural exploration and prediction of new BPTES analogs as glutaminase inhibitors
TL;DR: In this study, a multi-QSAR modeling is carried out on a series of BPTES analogs to search important molecular fingerprints or substructures that may help in classifying the probability of finding ‘active” and ‘inactive’ BPTes analogs.
References
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Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings
TL;DR: Experimental and computational approaches to estimate solubility and permeability in discovery and development settings are described in this article, where the rule of 5 is used to predict poor absorption or permeability when there are more than 5 H-bond donors, 10 Hbond acceptors, and the calculated Log P (CLogP) is greater than 5 (or MlogP > 415).
Journal ArticleDOI
p53 mutations in human cancers
TL;DR: The p53 mutational spectrum differs among cancers of the colon, lung, esophagus, breast, liver, brain, reticuloendothelial tissues, and hemopoietic tissues as mentioned in this paper.
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Multivariate Adaptive Regression Splines
TL;DR: In this article, a new method is presented for flexible regression modeling of high dimensional data, which takes the form of an expansion in product spline basis functions, where the number of basis functions as well as the parameters associated with each one (product degree and knot locations) are automatically determined by the data.
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Molecular properties that influence the oral bioavailability of drug candidates.
Daniel F. Veber,Stephen R. Johnson,Hung-Yuan Cheng,Brian R. Smith,Keith W. Ward,Kenneth D. Kopple +5 more
TL;DR: Reduced molecular flexibility, as measured by the number of rotatable bonds, and low polar surface area or total hydrogen bond count are found to be important predictors of good oral bioavailability, independent of molecular weight.
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In vivo activation of the p53 pathway by small-molecule antagonists of MDM2.
Lyubomir T. Vassilev,Binh Thanh Vu,Bradford Graves,Daisy Carvajal,Frank John Podlaski,Zoran Filipovic,Norman Kong,Ursula Kammlott,Christine Lukacs,Christian Klein,Nader Fotouhi,Liu Emily Aijun +11 more
TL;DR: In this article, the authors identify potent and selective small-molecule antagonists of MDM2 and confirm their mode of action through the crystal structures of complexes, leading to cell cycle arrest, apoptosis, and growth inhibition of human tumor xenografts.