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Abdullahi A.D.,International Islamic University Malaysia | Abdualkader A.M.,International Islamic University Malaysia | Abdualkader A.M.,University of Aleppo | Abdulsamat N.B.,International Islamic University Malaysia | Ingale K.,VLife Sciences Technologies Pvt. Ltd.
Tropical Journal of Pharmaceutical Research

Purpose: To identify the structural requirements for designing a lead key for insulin-like growth factor (IGF-1R) inhibition using group-based quantitative structure activity relationship (GQSAR) and molecular docking. Methods: GQSAR method requires fragmentation of molecules. The molecules in the current dataset were fragmented into three (R1, R2 and R3) by applying common fragmentation pattern, and fragment-based 2D descriptors were then calculated. GQSAR models were derived by applying various methods including multiple linear regressions and partial least square or k-nearest neighbor. Results: Four generated GQSAR models were selected based on the statistical significance of the model. It was found that the presence of flexible and non-aromatic groups on fragment R1 was conducive for inhibition. Additionally, the existence of amino groups as hydrogen bond donors at fragments R2 and R3 was fruitful for inhibition. Docking studies revealed the binding orientation adopted by the active compounds at several amino acid residues, including Met 1126, Arg, 1128, Met 1052, GLU 1050, Met 1112, Leu 1051, Met 1049, Val 1033, and Val 983 at ATP binding sites of IGF-1R kinase domain. Conclusion: The generated models provide a site-specific insight into the structural requirements for IGF-1R inhibition which can be used to design and develop potent inhibitors. © Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria. All rights reserved. Source

Ajmani S.,NovaLead Pharma Pvt. Ltd. | Ajmani S.,Jubilant Biosys Ltd. 96 | Kulkarni S.A.,NovaLead Pharma Pvt. Ltd. | Kulkarni S.A.,VLife Sciences Technologies Pvt. Ltd.
Molecular Informatics

Many literature reports suggest that drugs against multiple targets may overcome many limitations of single targets and achieve a more effective and safer control of the disease. However, design of multitarget drugs presents a great challenge. The present study demonstrates application of a novel Group based QSAR (GQSAR) method to assist in lead optimization of multikinase (PDGFR-beta, FGFR-1 and SRC) and scaffold hopping of multiserotonin target (serotonin receptor 1A and serotonin transporter) inhibitors. For GQSAR analysis, a wide variety of structurally diverse multikinase inhibitors (225 molecules) and multiserotonin target inhibitors (162 molecules) were collected from various literature reports. Each molecule in the data set was divided into four fragments (kinase inhibitors) and three fragments (serotonin target inhibitors) and their corresponding two-dimensional fragment descriptors were calculated. The multiresponse regression GQSAR models were developed for both the datasets. The developed GQSAR models were found to be useful for scaffold hopping and lead optimization of multitarget inhibitors. In addition, the developed GQSAR models provide important fragment based features that can form the building blocks to guide combinatorial library design in the search for optimally potent multitarget inhibitors. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

VLife Sciences Technologies Pvt. Ltd. | Entity website

Sun Pharma the top 5th largest speciality generic pharmaceutical company has signed up with VLife for genotoxicity prediction services. About Sun Pharma Industries Ltd ...

VLife Sciences Technologies Pvt. Ltd. | Entity website

VLife technologies Enabling higher research productivity VLife Products enable discovery research varying significantly in terms of objectives and available information. On the other hand, VLife Services cater to a wide cross section of research driven sectors and is exposed to diverse requirements ...

Ramteke M.P.,Advanced Center for Treatment | Shelke P.,Advanced Center for Treatment | Ramamoorthy V.,Advanced Center for Treatment | Somavarapu A.K.,Advanced Center for Treatment | And 5 more authors.
FEBS Letters

14-3-3 Proteins bind phosphorylated sequences in proteins and regulate multiple cellular functions. For the first time, we show that pure recombinant human 14-3-3 ζ, γ, ε and τ isofoms hydrolyze ATP with similar Km and kcat values. In sharp contrast the sigma isoform has no detectable activity. Docking studies identify two putative binding pockets in 14-3-3 zeta. Mutation of D124A in the amphipathic pocket enhances binding affinity and catalysis. Mutation of a critical Arg (R55A) at the dimer interface in zeta reduces binding and decreases catalysis. These experimental results coincide with a binding pose at the dimer interface. This newly identified function could be a moon lighting function in some of these isoforms. © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. Source

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