Abstract
Integrating physicochemical, drug metabolism, pharmacokinetics, ADME, and toxicity assays into drug discovery in order to reduce the attrition rates in clinical development is reviewed. The review is organized around three main decision points used in discovery including hit generation, lead optimization and final candidate selection stages. The preclinical strategies used at each decision point are discussed from a drug discovery perspective. Typically, preclinical data produced at these stages use lower throughput assays, smaller amounts of compounds and operate within a timeframe that is consistent with the iterative cycle of most drug discovery research projects. Understanding the false positive rates of these drug discovery preclinical assays is a must in reducing attrition rates in development.
Current Topics in Medicinal Chemistry
Title: ADME Optimization and Toxicity Assessment in Early- and Late-Phase Drug Discovery
Volume: 9 Issue: 11
Author(s): Gary W. Caldwell, Zhengyin Yan, Weimin Tang, Malini Dasgupta and Becki Hasting
Affiliation:
Abstract: Integrating physicochemical, drug metabolism, pharmacokinetics, ADME, and toxicity assays into drug discovery in order to reduce the attrition rates in clinical development is reviewed. The review is organized around three main decision points used in discovery including hit generation, lead optimization and final candidate selection stages. The preclinical strategies used at each decision point are discussed from a drug discovery perspective. Typically, preclinical data produced at these stages use lower throughput assays, smaller amounts of compounds and operate within a timeframe that is consistent with the iterative cycle of most drug discovery research projects. Understanding the false positive rates of these drug discovery preclinical assays is a must in reducing attrition rates in development.
Export Options
About this article
Cite this article as:
Caldwell W. Gary, Yan Zhengyin, Tang Weimin, Dasgupta Malini and Hasting Becki, ADME Optimization and Toxicity Assessment in Early- and Late-Phase Drug Discovery, Current Topics in Medicinal Chemistry 2009; 9 (11) . https://dx.doi.org/10.2174/156802609789630929
DOI https://dx.doi.org/10.2174/156802609789630929 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
-
Annotation of the Human Genome by High-Throughput Sequence Analysis of Naturally Occurring Proteins
Current Proteomics Perspective of MiRNAs in Clinical Glioblastoma Research
Current Signal Transduction Therapy The High Mobility Group A1 (HMGA1) Transcriptome in Cancer and Development
Current Molecular Medicine Docosahexaenoic Acid (DHA) Sensitizes Brain Tumor Cells to Etoposide-Induced Apoptosis
Current Molecular Medicine Fibrillar, Fibril-associated and Basement Membrane Collagens of the Arterial Wall: Architecture, Elasticity and Remodeling Under Stress
Current Pharmaceutical Design Improved Immunotoxins with Novel Functional Elements
Current Pharmaceutical Design Combination of Phytochemicals as Adjuvants for Cancer Therapy
Recent Patents on Anti-Cancer Drug Discovery FDG-PET/CT and SPECT/CT in Oncology
Current Medical Imaging Biomarkers to Assess the Targeting of DNA Repair Pathways to Augment Tumor Response to Therapy
Current Molecular Medicine subject Index To Volume 2
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Analysis of Fish IL-1β and Derived Peptide Sequences Indicates Conserved Structures with Species-Specific IL-1 Receptor Binding: Implications for Pharmacological Design
Current Pharmaceutical Design A Perspective on Clinical Islet Transplantation: Past, Present and Developments for Future
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Episomal Vectors for Gene Therapy
Current Gene Therapy Histopathology of Connective Tissue Disease-Associated Pleuropulmonary Disease
Current Respiratory Medicine Reviews Leptomeningeal Metastasis: Challenges in Diagnosis and Treatment
Current Cancer Therapy Reviews Antitumor Pharmacology - Quo Vadis ?
Current Medicinal Chemistry - Anti-Cancer Agents Ubiquitin Carboxyl Hydrolase L1 Significance for Human Diseases
Protein & Peptide Letters Inhibiting the “Undruggable” RAS/Farnesyltransferase (FTase) Cancer Target by Manumycin-related Natural Products
Current Medicinal Chemistry Germinal and Somatic Trisomy 21 Mosaicism: How Common is it, What are the Implications for Individual Carriers and How Does it Come About?
Current Genomics Editorial [Hot Topic: Mechanisms of Drug Sensitivity and Resistance in Cancer (Guest Editor: Lorraine ODriscoll)]
Current Cancer Drug Targets