Abstract
One of the greatest challenges facing the pharmaceutical industry today is the failure of promising new drug candidates due to unanticipated adverse effects discovered during preclinical animal safety studies and clinical trials. Late stage attrition increases the time required to bring a new drug to market, inflates development costs, and represents a major source of inefficiency in the drug discovery/development process. It is generally recognized that early evaluation of new drug candidates is necessary to improve the process. Building in vitro data sets that can accurately predict adverse effects in vivo would allow compounds with high risk profiles to be deprioritized, while those that possess the requisite drug attributes and a lower risk profile are brought forward. In vitro cytotoxicity assays have been used for decades as a tool to understand hypotheses driven questions regarding mechanisms of toxicity. However, when used in a prospective manner, they have not been highly predictive of in vivo toxicity. Therefore, the issue may not be how to collect in vitro toxicity data, but rather how to translate in vitro toxicity data into meaningful in vivo effects. This review will focus on the development of an in vitro toxicity screening strategy that is based on a tiered approach to data collection combined with data interpretation.
Keywords: In vitro, predictive, toxicity, screening, hepatocytes, drugs
Combinatorial Chemistry & High Throughput Screening
Title: Building a Tiered Approach to In Vitro Predictive Toxicity Screening: A Focus on Assays with In Vivo Relevance
Volume: 13 Issue: 2
Author(s): James M. McKim Jr.*
Affiliation:
- CeeTox Inc., 4717 Campus Dr., Kalamazoo, MI 49008, USA.,United States
Keywords: In vitro, predictive, toxicity, screening, hepatocytes, drugs
Abstract: One of the greatest challenges facing the pharmaceutical industry today is the failure of promising new drug candidates due to unanticipated adverse effects discovered during preclinical animal safety studies and clinical trials. Late stage attrition increases the time required to bring a new drug to market, inflates development costs, and represents a major source of inefficiency in the drug discovery/development process. It is generally recognized that early evaluation of new drug candidates is necessary to improve the process. Building in vitro data sets that can accurately predict adverse effects in vivo would allow compounds with high risk profiles to be deprioritized, while those that possess the requisite drug attributes and a lower risk profile are brought forward. In vitro cytotoxicity assays have been used for decades as a tool to understand hypotheses driven questions regarding mechanisms of toxicity. However, when used in a prospective manner, they have not been highly predictive of in vivo toxicity. Therefore, the issue may not be how to collect in vitro toxicity data, but rather how to translate in vitro toxicity data into meaningful in vivo effects. This review will focus on the development of an in vitro toxicity screening strategy that is based on a tiered approach to data collection combined with data interpretation.
Export Options
About this article
Cite this article as:
McKim Jr. M. James*, Building a Tiered Approach to In Vitro Predictive Toxicity Screening: A Focus on Assays with In Vivo Relevance, Combinatorial Chemistry & High Throughput Screening 2010; 13 (2) . https://dx.doi.org/10.2174/138620710790596736
DOI https://dx.doi.org/10.2174/138620710790596736 |
Print ISSN 1386-2073 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5402 |
Call for Papers in Thematic Issues
Artificial Intelligence Methods for Biomedical, Biochemical and Bioinformatics Problems
Recently, a large number of technologies based on artificial intelligence have been developed and applied to solve a diverse range of problems in the areas of biomedical, biochemical and bioinformatics problems. By utilizing powerful computing resources and massive amounts of data, methods based on artificial intelligence can significantly improve the ...read more
Eco-friendly Agents for Biological Control of Pathogenic Diseases
The discovery of an alternative biological approach to disease management includes work on medicinal products derived from natural sources as a starting point for the development of eco-friendly agents for these diseases and the injuries they cause, as well as reducing human contact with hazardous chemicals and their residues. We ...read more
Emerging trends in diseases mechanisms, noble drug targets and therapeutic strategies: focus on immunological and inflammatory disorders
Recently infectious and inflammatory diseases have been a key concern worldwide due to tremendous morbidity and mortality world Wide. Recent, nCOVID-9 pandemic is a good example for the emerging infectious disease outbreak. The world is facing many emerging and re-emerging diseases out breaks at present however, there is huge lack ...read more
Exploring Spectral Graph Theory in Combinatorial Chemistry
Scope of the Thematic Issue: Combinatorial chemistry involves the synthesis and analysis of a large number of diverse compounds simultaneously. Traditional methods rely on brute force experimentation, which can be time-consuming and resource-intensive. Spectral Graph Theory, a branch of mathematics dealing with the properties of graphs in relation to the ...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
Related Articles
-
An HHV-8 Positive HIV Negative Multicentric Castleman’s Disease, who Responded well to Rituximab Alone
Cardiovascular & Hematological Disorders-Drug Targets Anti-inflammatory Phytochemicals for Chemoprevention of Colon Cancer
Current Cancer Drug Targets Inpatient Care of the HIV Infected Patient in the Highly Active Antiretroviral Therapy (HAART) Era
Current HIV Research Combined Anticancer Therapies: An Overview of the Latest Applications
Anti-Cancer Agents in Medicinal Chemistry Cancer Resistance to Type II Topoisomerase Inhibitors
Current Medicinal Chemistry Reverse Pharmacognosy: Application of Selnergy, a New Tool for Lead Discovery. The Example of ε-Viniferin
Current Drug Discovery Technologies SAR, QSAR and Docking of Anticancer Flavonoids and Variants: A Review
Current Topics in Medicinal Chemistry Novel Rational Drug Design Strategies with Potential to Revolutionize Malaria Chemotherapy
Current Medicinal Chemistry Pleural Fluid Analysis for Evaluating Pleural Effusions
Current Respiratory Medicine Reviews Human Chorionic Gonadotropin: A Model Molecule For Oligopeptide-Based Drug Discovery
Endocrine, Metabolic & Immune Disorders - Drug Targets Role of PARP Inhibitors in Cancer Biology and Therapy
Current Medicinal Chemistry HDAC as a Therapeutic Target for Treatment of Endometrial Cancers
Current Pharmaceutical Design HPV Cervical Infection and Immunodysregulation: Synergistic Risks for Neoplasia-Review
Current Women`s Health Reviews VEGF, BMP-7, Matrigel<sup>TM</sup>, Hyaluronic Acid, In Vitro Cultured Chondrocytes and Trephination for Healing of the Avascular Portion of the Meniscus. An Experimental Study in Sheep
Current Stem Cell Research & Therapy Between Bench and Bed Side: PI3K Inhibitors
Current Molecular Pharmacology Targeting Gene Therapy for Prostate Cancer
Current Pharmaceutical Design Developments of DNA-dependent Protein Kinase Inhibitors as Anticancer Agents
Mini-Reviews in Medicinal Chemistry The Role of Image Guided Radiotherapy in the Treatment of Soft Tissue Sarcoma
Current Cancer Therapy Reviews Cashew Gum A Versatile Hydrophyllic Polymer: A Review
Current Drug Therapy Topotecan and Irinotecan in the Treatment of Pediatric Solid Tumors
Current Pediatric Reviews