Main description:

This practical referene for drug developers addresses the most common antitarget-related side effects, including hepatic, cardiovascular, kinase- and GPCR-mediated toxicity. Current strategies how to manage side effects as well as several case studies are included.

Contents:

SECTION 1: GENERAL CONCEPT FOR TARGET-BASED SAFETY ASSESSMENT Analysis of marketed drugs: The utility of AERS for early drug discovery How to interpret anti-target data: Introduction of the concept of "coverage" In silico applications to find unknown side effects Translational value of preclinical safety assessment: how to consider targets in SOCs Pathological conditions associated with the disturbance of 5HT receptors SECTION 2: HEPATIC SIDE EFFECTS DILI: Mechanisms & Detection Hepatotox assays Transporters in the liver SECTION 3: CARDIOVASCULAR SIDE EFFECTS Chronotropic effects, ionotropic effects, general hemodynamic effects Cav1.2 Nav 1.5 Circulating biomarkers for cardiotoxicity: reverse translation from human to preclinical species hERG SECTION 4: INASE ANTITARGETS Introduction to Kinase Anti-Targets Kinase Targets with CV safety issues Kinase Signalling and AEs - Preclinical connection Kinase Signalling and AEs - Clinical Connection Case Study I Case Study II SECTION 5: EXAMPLES Labels & blackbox warnings Rimonabant Torcetrapib/Dalcetrapib Pharmacology of suicidal intent