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 In spite of this, various drugs have failed in clinical trials or withdrawn from market because of human safety issues related to cardiotoxicity, hepatotoxicity, neurotoxicity and teratogenicity.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.
Keywords: Pluripotent Stem Cells, Teratogenicity, Cardiotoxicity, Hepatotoxicity, Neurotoxicity, New Drug Discovery, Alternative Testing Strategies.
Current Medicinal Chemistry
Title:Human Embryonic and Induced Pluripotent Stem Cell Based Toxicity Testing Models: Future Applications in New Drug Discovery
Volume: 23 Issue: 30
Author(s): Vaibhav Shinde, Poornima Sureshkumar, Isaia Sotiriadou, Jurgen Hescheler and Agapios Sachinidis
Affiliation:
Keywords: Pluripotent Stem Cells, Teratogenicity, Cardiotoxicity, Hepatotoxicity, Neurotoxicity, New Drug Discovery, Alternative Testing Strategies.
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.
Export Options
About this article
Cite this article as:
Shinde Vaibhav, Sureshkumar Poornima, Sotiriadou Isaia, Hescheler Jurgen and Sachinidis Agapios, Human Embryonic and Induced Pluripotent Stem Cell Based Toxicity Testing Models: Future Applications in New Drug Discovery, Current Medicinal Chemistry 2016; 23 (30) . https://dx.doi.org/10.2174/0929867323666160627113436
DOI https://dx.doi.org/10.2174/0929867323666160627113436 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Antipsychotic-like Effects of Cannabidiol and Rimonabant: Systematic Review of Animal and Human Studies
Current Pharmaceutical Design Estrogen, A Double-Edged Sword: Modulation of TH1- and TH2-Mediated Inflammations by Differential Regulation of TH1 / TH2 Cytokine Production
Current Drug Targets - Inflammation & Allergy Omentin: Linking Metabolic Syndrome and Cardiovascular Disease
Current Vascular Pharmacology Advances in Nanomaterials for Diagnosis and Therapy of Leukemia
Recent Patents on Nanomedicine Aptamers: Potential Applications to Pancreatic Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry Role of the Endocannabinoid System in the Neuroendocrine Responses to Inflammation
Current Pharmaceutical Design The Role of LH in Ovarian Stimulation
Current Pharmaceutical Biotechnology Role of α- and β-adrenergic Mechanisms in the Pathogenesis of Pulmonary Injuries Characterized by Edema, Inflammation and Fibrosis
Cardiovascular & Hematological Disorders-Drug Targets Positional Cloning in Mice and Its Use For Molecular Dissection of Inflammatory Arthritis
Current Pharmaceutical Biotechnology Rhinosinusitis in the Pediatric Patient with Cystic Fibrosis
Current Pediatric Reviews Special Invited Article Concussion, Sports and Psychiatry
Adolescent Psychiatry Current Advances in L-DOPA and DOPA-Peptidomimetics: Chemistry, Applications and Biological Activity
Current Medicinal Chemistry Cannabinoids and Memory; Animal Studies
Current Drug Targets - CNS & Neurological Disorders Recent Patents in Cartilage Regeneration
Recent Patents on Regenerative Medicine Is the Vascular System a Main Target for Thyroid Hormones? From Molecular and Biochemical Findings to Clinical Perspectives
Current Vascular Pharmacology Interferons: Mechanisms, Biological Activities and Survey of their Use in Human Diseases
Current Bioactive Compounds Aldose Reductase, Still a Compelling Target for Diabetic Neuropathy
Current Drug Targets Signal Transduction via Cannabinoid Receptors
CNS & Neurological Disorders - Drug Targets TGFb and its Smad Connection to Cancer
Current Genomics Pharmacological and Cellular Therapies to Prevent Restenosis after Percutaneous Transluminal Angioplasty and Stenting
Cardiovascular & Hematological Agents in Medicinal Chemistry