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Modeling drug- and chemical-induced hepatotoxicity with systems biology approaches
Published on Jul 21, 20141521 Views
How can serious liver safety events be detected more efficiently and effectively in drug development? Can serious events we delineated from benign events? Could mechanistic modeling approaches help
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Chapter list
Modeling drug- and chemical-induced hepatotoxicity with systems biology approaches00:00
The DILI-sim Initiative Is a Partnership between the Hamner Institutes and Pharmaceutical Companies to Minimize DILI00:15
The DILI-sim Team and the SAB01:03
Goals of DILI-sim and Intended Applications of DILIsym®01:37
DILIsym®: 'Middle Out' and Multi-Scale03:30
DILIsym® Overview05:15
Key Areas for DILIsym® Data Inputs and Simulation Results Comparators06:34
Examples of DILIsym® Applications08:00
Entolimod (Cleveland BioLabs) Project Objectives08:39
DILIsym® Overview10:07
Baseline Human Simulations Indicate Minimal Hepatocyte Loss with Entolimod10:23
Minimal Range of Hepatocyte Loss Predicted for Entolimod Using Population Sample12:05
Project Summary12:41
Examples of DILIsym® Applications13:21
Modeling for Susceptibility Factors: The Case Study with Troglitazone13:37
Troglitazone (TGZ)13:54
DILIsym® Overview14:50
Mechanisms of DILI: Transport protein-mediated Bile acid-drug interaction15:00
Construction of Human Sample Population (SimPopsTM)15:44
Bile Acid Transport Inhibition Alone Predicted TGZ Hepatotoxicity in Human SimPopsTM16:31
Bile Acid Transport Inhibition Alone Predicted TGZ Hepatotoxicity in Human SimPopsTM17:08
Mechanistic Model Reasonably Predicted Delayed Presentation of TGZ Hepatotoxicity18:10
Susceptibility Factors for TGZ Hepatotoxicity18:51
Species Difference in TGZ Hepatotoxicity Predicted19:31
Conclusions and Perspectives20:12
Thank you20:47