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Your search keyword '"D. Jansson"' showing total 2 results
Start Over Author "D. Jansson" Publisher american chemical society
2 results on '"D. Jansson"'

1. Applications in Forensic Proteomics: Protein Identification and Profiling

Author

Eric D. Merkley, Brooke L. D. Kaiser, Helen Kreuzer, Carrie Nicora, Marina Gritsenko, Anna Lipton, Karen L. Wahl, Kristin E. Burnum-Johnson, Heather E. McKiernan, Catherine O. Brown, Luciano Chaves Arantes, Phillip B. Danielson, Kevin M. Legg, Wenke Liu, Erin Butler, Heyi Yang, David Fenyö, Donald Siegel, Simona Francese, Cristina Russo, Fanny Chu, Katelyn E. Mason, Deon S. Anex, Phillip H. Paul, Bradley R. Hart, Michael Buckley, Stephen R. Cendrowski, Alaine M. Garrett, Suzanne R. Kalb, François Becher, R. Zeleny, A. Rummel, D. Jansson, B. G. Dorner, Kristin H. Jarman, Eric D. Merkley, Brooke L. D. Kaiser, Helen Kreuzer, Carrie Nicora, Marina Gritsenko, Anna Lipton, Karen L. Wahl, Kristin E. Burnum-Johnson, Heather E. McKiernan, Catherine O. Brown, Luciano Chaves Arantes, Phillip B. Danielson, Kevin M. Legg, Wenke Liu, Erin Butler, Heyi Yang, David Fenyö, Donald Siegel, Simona Francese, Cristina Russo, Fanny Chu, Katelyn E. Mason, Deon S. Anex, Phillip H. Paul, Bradley R. Hart, Michael Buckley, Stephen R. Cendrowski, Alaine M. Garrett, Suzanne R. Kalb, François Becher, R. Zeleny, A. Rummel, D. Jansson, B. G. Dorner, and Kristin H. Jarman

Subjects
Bioinformatics, Forensic biology, Forensic proteomics, Mass spectrometry--Forensic applications, Chemistry, Forensic
Published
2019

2. Optimization of the in vitro cardiac safety of hydroxamate-based histone deacetylase inhibitors.

Author

Shultz MD, Cao X, Chen CH, Cho YS, Davis NR, Eckman J, Fan J, Fekete A, Firestone B, Flynn J, Green J, Growney JD, Holmqvist M, Hsu M, Jansson D, Jiang L, Kwon P, Liu G, Lombardo F, Lu Q, Majumdar D, Meta C, Perez L, Pu M, Ramsey T, Remiszewski S, Skolnik S, Traebert M, Urban L, Uttamsingh V, Wang P, Whitebread S, Whitehead L, Yan-Neale Y, Yao YM, Zhou L, and Atadja P

Subjects
Acrylamides chemical synthesis, Acrylamides pharmacology, Animals, Antineoplastic Agents chemical synthesis, Antineoplastic Agents pharmacology, Drug Screening Assays, Antitumor, ERG1 Potassium Channel, HCT116 Cells, Half-Life, Histone Deacetylase Inhibitors chemical synthesis, Histone Deacetylase Inhibitors pharmacology, Humans, Hydroxamic Acids chemical synthesis, Hydroxamic Acids pharmacology, In Vitro Techniques, Mice, Mice, Nude, Microsomes, Liver metabolism, Models, Molecular, Neoplasm Transplantation, Patch-Clamp Techniques, Radioligand Assay, Rats, Rats, Sprague-Dawley, Stereoisomerism, Structure-Activity Relationship, Tissue Distribution, Transplantation, Heterologous, Acrylamides toxicity, Antineoplastic Agents toxicity, Ether-A-Go-Go Potassium Channels antagonists & inhibitors, Histone Deacetylase Inhibitors toxicity, Hydroxamic Acids toxicity
Abstract

Histone deacetylase (HDAC) inhibitors have shown promise in treating various forms of cancer. However, many HDAC inhibitors from diverse structural classes have been associated with QT prolongation in humans. Inhibition of the human ether a-go-go related gene (hERG) channel has been associated with QT prolongation and fatal arrhythmias. To determine if the observed cardiac effects of HDAC inhibitors in humans is due to hERG blockade, a highly potent HDAC inhibitor devoid of hERG activity was required. Starting with dacinostat (LAQ824), a highly potent HDAC inhibitor, we explored the SAR to determine the pharmacophores required for HDAC and hERG inhibition. We disclose here the results of these efforts where a high degree of pharmacophore homology between these two targets was discovered. This similarity prevented traditional strategies for mitigating hERG binding/modulation from being successful and novel approaches for reducing hERG inhibition were required. Using a hERG homology model, two compounds, 11r and 25i, were discovered to be highly efficacious with weak affinity for the hERG and other ion channels.

Published
2011
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