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TimTec in Publications
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Jenny M. Pedersen, Pär Matsson, Christel A. S. Bergström, Ulf Norinder, Janet Hoogstraate and Per Artursson J. Med. Chem., 2008, 51 (11), pp 3275–3287 Publication Date (Web): May 6, 2008 (Article) DOI: 10.1021/jm7015683 A total of 669 molecular decriptors, representing mainly the molecular size, flexibility, connectivity, polarity, charge, and hydrogen bonding potential of the molecules, were calculated from the 3D structures using DragonX version 3.0 (Talete, Milano, Italy), ADMETPredictor version 1.2.4 (SimulationsPlus, Lancaster, CA), and HYBOT ( MOLPRO-2001, TimTec, Newark, DE). Abstract The chemical space of registered oral drugs was explored for inhibitors of the human multidrug-resistance associated protein 2 (MRP2; ABCC2), using a data set of 191 structurally diverse drugs and drug-like compounds. The data set included a new reference set of 75 compounds, for studies of hepatic drug interactions with transport proteins, CYP enzymes, and compounds associated with liver toxicity. The inhibition of MRP2-mediated transport of estradiol-17β-d-glucuronide was studied in inverted membrane vesicles from Sf9 cells overexpressing human MRP2. A total of 27 previously unknown MRP2 inhibitors were identified, and the results indicate an overlapping but narrower inhibitor space for MRP2 compared with the two other major ABC efflux transporters P-gp (ABCB1) and BCRP (ABCG2). In addition, 13 compounds were shown to stimulate the transport of estradiol-17β-d-glucuronide. The experimental results were used to develop a computational model able to discriminate inhibitors from noninhibitors according to their molecular structure, resulting in a predictive power of 86% for the training set and 72% for the test set. The inhibitors were in general larger and more lipophilic and presented a higher aromaticity than the noninhibitors. The developed computational model is applicable in an early stage of the drug discovery process and is proposed as a tool for prediction of MRP2-mediated hepatic drug interactions and toxicity.
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TimTec in Publications
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The screen of TimTec compounds identified 6 potent TNF-α inducers, which are available from our stock.
Identification of novel formyl peptide receptor-like 1 agonists that induce macrophage tumor necrosis factor alpha production. Schepetkin IA, Kirpotina LN, Tian J, Khlebnikov AI, Ye RD, Quinn MT. Mol Pharmacol. 2008 Aug;74(2):392-402. Abstract Development of immunomodulatory agents that enhance innate immune responses represents a promising strategy for combating infectious diseases. In the present studies, we screened a series of 71 arylcarboxylic acid hydrazide derivatives for their ability to induce macrophage tumor necrosis factor a (TNF-a) production and identified 6 such compounds, including one compound previously shown to be a formyl peptide receptor (FPR/FPRL1) agonist. The two most potent compounds [Compound 1: nicotinic acid [5-(3-bromophenyl)-2-furyl]methylene-hydrazide; Compound 2:4-fluoro-benzoic acid [5-(3-trifluoromethyl-phenyl)-2-furyl]methylene-hydrazide] were selected for further analysis. These compounds induced denovo production of TNF-a in a dose- and time-dependent manner in human and murine monocyte/macrophage cell lines and in primary macrophages. These compounds also induced mobilization of intracellular Ca2+, production of reactive oxygen species, and chemotaxis in human and murine phagocytes.Induction of macrophage TNF-a production was pertussis toxinsensitive, and analysis of the cellular target of these compounds showed that they were FPRL1-specific agonists and that this response was blocked byFPR/FPRL1 and FPRL1-specific antagonists. Additionally, pharmacophore modeling showed a high degree of similarity for lowenergy conformations of these two compounds to the current pharmacophore model for FPR ligands (Edwards et al., 2005 Overall, these compounds represent novel FPRL1 agonists that induce TNF-a, a response distinct from those induced by other known FPR and FPRL1 agonists. Chemical structures of the most potent TNF-α inducers ST013006 MW 370.21 MF C17H12BrN3O2 N-{(1E)-2-[5-(3-bromophenyl)(2-furyl)]-1-azavinyl}-3-pyridylcarboxamide 
ST020452 MW 376.31 MF C19H12F4N2O2 N-((1Z)-2-{5-[3-(trifluoromethyl)phenyl](2-furyl)}-1-azavinyl)(4-fluorophenyl) carboxamide 
ST020520
MW 404.42 MF C23H20N2O5 2H-benzo[3,4-d]1,3-dioxolan-5-yl-N-{(1Z)-2-[3-methoxy-4-(phenylmethoxy)phenyl] -1-azavinyl}carboxamide 
ST020527 MW 359.21 MF C18H12Cl2N2O2 N-{(1E)-2-[5-(2,3-dichlorophenyl)(2-furyl)]-1-azavinyl}benzamide 
ST041063 MW 413.77 MF C19H12ClN3O6 2H-benzo[3,4-d]1,3-dioxolan-5-yl-N-{(1Z)-2-[5-(2-chloro-4-nitrophenyl)(2-furyl )]-1-azavinyl}carboxamide 
ST073755 MW 312.328 MF C16H16N4O3 N-{(1E)-2-[4-(dimethylamino)phenyl]-1-azavinyl}(4-nitrophenyl)carboxamide 
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TimTec in Publications
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Aurélien Monge, Alban Arrault, Christophe Marot et Luc Morin-Allory.
Analysis of a Virtual Database of Five Million Commercially Available Compounds. Institut de Chimie Organique et Analytique, UMR CNRS 6005, Université d’Orléans BP 6759, 45067 ORLEANS Cedex 2, France. Download PDF Original link |
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TimTec in Publications
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TimTec Natural Product Library was screened to identify compounds that significantly reduce infectivity without cytotoxicity. NPL collection counted 280 compounds at the time of the moderate-throughput screening. MTS assay is adaptable to different virus systems. |
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TimTec in Publications
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Protein kinases always remain in research focus while searching for small molecules with anti-cancer activity. The following article would be an excellent guidance or supplement to designing and/or finding kinase target-oriented library.
Prien, O. Target-Family-Oriented Focused Libraries for Kinases-Conceptual Design Aspects and Commercial Availability. ChemBioChem 2005, 6, 500-505.
In the article Dr. Prien from European Research Center at Schering AG provides informative overview of two major design approaches used in the creation of target-family oriented libraries: design based on structural properties and design based on descriptor properties.
There are specific examples of building a library based on preferred scaffolds, privileged structures, lead compounds, and a number of computational descriptors. Computational methods are discussed. The article suggests integration of different approaches with reliance on essential medicinal chemistry expertise.
TimTec is identified as one of the major suppliers of directed libraries on the market with its ActiTarg-K, kinase inhibitors collection. TimTec has grown kinase inhibitor library since 2005. ActiTarg-K now includes over 6,600 compounds with its 960 compounds - top structural diversity selection - still offered as a comprehensive in size subset.
Visit ActiTarg-K, Kinase Modulators page
Contact TimTec
Receive ActiTarg-K on a CDRom or download compound databases here 
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