Total 13 results found.
Tag: 2012 Ordering

Cytochrome P450 3A4 Inhibition by Ketoconazole: Tackling the Problem of Ligand Cooperativity Using Molecular Dynamics Simulations and Free-Energy Calculations Bren U, Oostenbrink BC J. Chem. Inf. Model., 2012, 52, 1573-1582 DOI:10.1021/ci300118x

QM/MM-Based Fitting of Atomic Polarizabilities for Use in Condensed-Phase Biomolecular Simulation Vosmeer CR, Rustenburg AS,  Rice JE, Horn HW, Swope WC, Geerke DP J. Chem. Theory Comput. 2012 DOI: 10.1021/ct300085z

Prof. dr. Nico Vermeulen from the Division of Molecular Toxicology and his staff members Dr. Jan Commandeur and Dr. Chris Vos have obtained a large grant for an Innovative Medicine Initiative project. With this funding, they aim to develop new test systems for drugs causing drug-induced liver injury in humans.

The Innovative Medicine Initiative project is entitled 'Mechanism-Based Integrated Systems for the Prediction of Drug-Induced Liver Injury'. It will address the improvement of existing and the development of novel in vivo and in vitro test systems for the prediction of drug-induced liver injury in humans. Drug-induced liver injury is main leading cause of liver failure and transplantation in western countries.

The total budget of the Innovative Medicine Initiative project is 34M EUR. Of this amount, 1.5M EUR is covering a 5-year contribution to the Division of Molecular Toxicology. With this grant, the division can hire 3 PhD students and a post-doc researcher and support them with significant additional funds for bench fees and equipment. This research project is the third Innovative Medicine Initiative project of group of Nico Vermeulen. In 2010, the IMI-SafeSciMET and IMI-eTOX projects were started.

Non-clinical test cascade

The consortium working on 'Mechanism-Based Integrated Systems for the Prediction of Drug-Induced Liver Injury' comprises key opinion leaders from universities, the biotechnology sector and the pharmaceutical industry. They share a common goal of improving the limited predictability or current drug-induced liver injury test systems.

The ultimate purpose is to develop a novel, non-clinical test cascade for this disease. This test cascade will be mechanism-based and/or of physiological, pharmacological and pathological relevance to drug-induced liver injury. The goal is to utilize the test cascade within the pharmaceutical industry to enable selection of drug candidates that have reduced propensity to cause drug-induced liver injury in humans.

Click here for more details on this project.

The role of protein plasticity in computational rationalization studies on regioselectivity in testosterone hydroxylation by Cytochrome P450 BM3 mutants De Beer SB, van Bergen LA, Keijzer K, Rea V, Venkataraman H, Guerra CF, Bickelhaupt FM, Vermeulen NP, Commandeur JN, Geerke DP Curr. Drug Metab. 2012

Regio- and Stereoselective Hydroxylation of Optically Active α-Ionone Enantiomers by Engineered Cytochrome P450 BM3 Mutants Harini Venkataraman, Stephanie B. A. de Beer, Daan P. Geerke, Nico P. E. Vermeulen, Jan N. M. Commandeur Advanced Synthesis & Catalysis, Volume 354, Issue 11-12, pages 2172–2184, August 13, 2012

Free Energy Calculations Give Insight into the Stereoselective Hydroxylation of α-Ionones by Engineered Cytochrome P450 BM3 Mutants; Stephanie B.A. de Beer, Harini Venkataraman, Daan P. Geerke, Chris Oostenbrink, Nico P.E. Vermeulen; J. Chem. Inf. Model., 2012, 52 (8), pp 2139–2148; DOI: 10.1021/ci300243n

Combination of biotransformation by P450 BM3 mutants with on-line post-column bioaffinity and mass spectrometric profiling as a novel strategy to diversify and characterize p38α kinase inhibitors; Vanina Rea , David Falck , Jeroen Kool , Frans J. J. de Kanter , Jan N. M. Commandeur , Nico P. E. Vermeulen , Wilfried M. A. Niessen and Maarten Honing ; Med. Chem. Commun., 2013,4, 371-377 DOI: 10.1039/C2MD20283B

Mass Spectrometric Characterization of Protein Adducts of Multiple P450-Dependent Reactive Intermediates of Diclofenac to Human Glutathione-S-transferase P1-1; Jan Simon Boerma , Sanja Dragovic , Nico P. E. Vermeulen , and Jan N. M. Commandeur; Chem. Res. Toxicol., 2012, 25 (11), pp 2532–2541DOI: 10.1021/tx300334w

Yeast as a humanized model organism for biotransformation-related toxicity Van Leeuwen JS, Vermeulen NP, Chris Vos. Curr. Drug Metab. 2012, Dec 1; 13(10): 1464-75. Pubmed

H. Venkataraman, S.B.A. de Beer, L.A.H. van Bergen, N. van Essen, D.P. Geerke, N.P.E. Vermeulen and J.N.M. Commandeur "A single active site mutation inverts stereoselectivity of 16-hydroxylation of testosterone catalyzed by engineered Cytochrome P450 BM3" Chem. Bio. Chem. 2012, DOI: 10.1002/cbic.201100750
S. Canzar, M. El-Kebir, R. Pool, K. Elbassioni, A.K. Malde, A.E. Mark, D.P. Geerke, L. Stougie and G.W. Klau "Charge Group Partitioning in Biomolecular Simulation" In: Lecture Notes on Computer Science: Research in Computational Molecular Biology, 16th Annual International RECOMB Conference, 2012; in press

van Leeuwen J.S., Unlü B., Vermeulen N.P., Vos J.C. (2012): Differential involvement of mitochondrial dysfunction, cytochrome P450 activity, and active transport in the toxicity of structurally related NSAIDs. Toxicol in Vitro, Mar:26(2):197-205.