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Aggregate Culture of Human Embryonic Stem Cell-Derived Hepatocytes in Suspension Are an Improved In Vitro Model for Drug Metabolism and Toxicity Testing

Srikumar Sengupta, Brian Patrick Johnson, Scott Allen Swanson, Ron Stewart, Christopher Alan Bradfield and James Alexander Thomson.

in Toxicological Sciences

July 2014; p ublished online April 2014 .

Journal Article. Subjects: Medical Toxicology; Clinical Pharmacology and Therapeutics. 4664 words.

Early phase drug development relies on primary human hepatocytes for studies of drug metabolism, cytotoxicity, and drug-drug interactions. However, primary human hepatocytes rapidly lose...

Chemical Tuning Enhances Both Potency Toward Nrf2 and In Vitro Therapeutic Index of Triterpenoids

Ian M. Copple, Luke M. Shelton, Joanne Walsh, Denise V. Kratschmar, Adam Lister, Alex Odermatt, Christopher E. Goldring, Albena T. Dinkova-Kostova, Tadashi Honda and B. Kevin Park.

in Toxicological Sciences

August 2014; p ublished online August 2014 .

Journal Article. Subjects: Medical Toxicology; Clinical Pharmacology and Therapeutics. 4312 words.

The transcription factor Nrf2 protects against a number of experimental pathologies, and is a promising therapeutic target. The clinical investigation of a potent Nrf2-inducing agent, the...

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Initial Biological Qualification of SBDP-145 as a Biomarker of Compound-Induced Neurodegeneration in the Rat

Michael L. Pritt, D. Greg Hall, William H. Jordan, Darryl W. Ballard, Kevin K.W. Wang, Uwe R. Müller and David E. Watson.

in Toxicological Sciences

October 2014; p ublished online October 2014 .

Journal Article. Subjects: Medical Toxicology; Clinical Pharmacology and Therapeutics. 6051 words.

Detection of compound-related neurodegeneration is currently limited to brain histopathology in veterinary species and functional measurements such as electroencephalography and observation...

P450-Mediated O-Demethylated Metabolite Is Responsible for Rat Hepatobiliary Toxicity of Pyridyltriazine-Containing PI3K Inhibitors

Raju Subramanian, Divesh Aidasani, Keith Bailey, Dan Branstetter, Nancy Everds, Jian Jiang, Mark H. Norman, Ronya Primack, Gary L. Skiles, Irene Soto, Markian M. Stec, Mylo Wagner, Tian Wu, Xiaochun Zhu and Hervé Lebrec.

in Toxicological Sciences

November 2014; p ublished online August 2014 .

Journal Article. Subjects: Medical Toxicology; Clinical Pharmacology and Therapeutics. 7187 words.

The dysregulation of phosphatidylinositol 3-kinase (PI3K)-dependent pathways is implicated in several human cancers making it an attractive target for small molecule PI3K inhibitors. A...