Universität zu Köln

Shinde, Vaibhav, Sureshkumar, Poornima, Sotiriadou, Isaia, Hescheler, Juergen and Sachinidis, Agapios (2016). Human Embryonic and Induced Pluripotent Stem Cell Based Toxicity Testing Models: Future Applications in New Drug Discovery. Curr. Med. Chem., 23 (30). S. 3495 - 3510. SHARJAH: BENTHAM SCIENCE PUBL LTD. ISSN 1875-533X

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Abstract

New drug discovery (NDD) is a fascinating discipline encompassing different facets of medicine, pharmacology, biotechnology and chemistry. NDD is very often restricted by efficacy or safety problems of the new clinical candidate in human patients. Drug regulatory authorities have provided various guidelines for advancement of safe new chemical entities (NCEs) in clinical trials which must be strictly followed. In spite of this, various drugs have failed in clinical trials or withdrawn from market because of human safety issues related to cardiotoxicity, hepatotoxicity, neurotoxicity and teratogenicity. The failure of safety prediction was pointed to species specificity issues, lack of mechanistic toxicity data and inadequate clinical trials. These drugs not only affect human health but also cause loss of resources and time. The species specificity issues are partially addressed by use of primary human cells but their availability is very limited. Human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) offer sources for generation of an unlimited number of human somatic cells. The emergence of mechanistic models for toxicity testing with transcriptomics, proteomics along with toxicokinetics readouts based on hESCs and hiPSCs is paving the way to design new human relevant testing strategies. Introduction of these models at the timeframe of lead selection and optimization in parallel with in vitro pharmacokinetic studies will significantly reduce compound attrition rate by selection of safer lead molecules. We focused on upcoming hESCs and hiPSCs based toxicity testing models and their future role to address safety gaps of present drug discovery and development.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Shinde, Vaibhav UNSPECIFIED UNSPECIFIED UNSPECIFIED Sureshkumar, Poornima UNSPECIFIED UNSPECIFIED UNSPECIFIED Sotiriadou, Isaia UNSPECIFIED UNSPECIFIED UNSPECIFIED Hescheler, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Sachinidis, Agapios UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-288854
DOI:	10.2174/0929867323666160627113436
Journal or Publication Title:	Curr. Med. Chem.
Volume:	23
Number:	30
Page Range:	S. 3495 - 3510
Date:	2016
Publisher:	BENTHAM SCIENCE PUBL LTD
Place of Publication:	SHARJAH
ISSN:	1875-533X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HEPATOCYTE-LIKE CELLS; OF-THE-ART; DEVELOPMENTAL NEUROTOXICITY; NEURONAL DIFFERENTIATION; FUNCTIONAL HEPATOCYTES; ALTERNATIVE METHODS; GENE-EXPRESSION; CULTURE-SYSTEM; CARDIAC TISSUE; CARDIOMYOCYTES Multiple languages Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/28885