Abstract
For many years, the most frequently optimized qualities of a screening library, or corporate compound collection, were size and diversity. Maximizing the number of diverse hits is the fundamental goal of such strategies. The ostensible justification that "bigger is better" is based on the large, estimated size of small-molecule space and the hypothesis that the notoriously low hit rates from high-throughput screening (HTS) could be overcome by brute force: i.e. by screening more compounds. Published, detailed studies about the success (or failure) of the brute-force strategy are rare, but it is well-known that it did not fulfill expectations. As a result, published reports in recent years have increasingly described methods for designing, selecting or synthesizing gene family-focused or -biased libraries. Moreover, many of the larger compound suppliers now sell such libraries, reflecting the growing interest in them from both the pharmaceutical and biotechnology markets. The trend towards gene family-focused libraries marks the emergence of a different hypothesis about how to increase HTS hit rates and also reflects an increasingly pragmatic focus on the management of screening libraries. An important, underlying assumption in this trend is that a high-quality, generalpurpose screening library of manageable size is neither realizable nor desirable. Whether a biasing strategy based on a specific gene family will do a better job of meeting both the scientific and business needs of the drug discovery enterprise still remains to be seen, but it is certainly an active area of current research. This review focuses on the "who, what, why, when, and how" of the design of gene family-focused libraries. Particular attention is given to reports that discuss not only the techniques used, but also any results obtained.
Keywords: Focused library design, gene-family, kinase, GPCR, drug discovery, high-throughput screening
Current Topics in Medicinal Chemistry
Title: Recent Developments in Focused Library Design: Targeting Gene-Families
Volume: 6 Issue: 1
Author(s): Jennifer L. Miller
Affiliation:
Keywords: Focused library design, gene-family, kinase, GPCR, drug discovery, high-throughput screening
Abstract: For many years, the most frequently optimized qualities of a screening library, or corporate compound collection, were size and diversity. Maximizing the number of diverse hits is the fundamental goal of such strategies. The ostensible justification that "bigger is better" is based on the large, estimated size of small-molecule space and the hypothesis that the notoriously low hit rates from high-throughput screening (HTS) could be overcome by brute force: i.e. by screening more compounds. Published, detailed studies about the success (or failure) of the brute-force strategy are rare, but it is well-known that it did not fulfill expectations. As a result, published reports in recent years have increasingly described methods for designing, selecting or synthesizing gene family-focused or -biased libraries. Moreover, many of the larger compound suppliers now sell such libraries, reflecting the growing interest in them from both the pharmaceutical and biotechnology markets. The trend towards gene family-focused libraries marks the emergence of a different hypothesis about how to increase HTS hit rates and also reflects an increasingly pragmatic focus on the management of screening libraries. An important, underlying assumption in this trend is that a high-quality, generalpurpose screening library of manageable size is neither realizable nor desirable. Whether a biasing strategy based on a specific gene family will do a better job of meeting both the scientific and business needs of the drug discovery enterprise still remains to be seen, but it is certainly an active area of current research. This review focuses on the "who, what, why, when, and how" of the design of gene family-focused libraries. Particular attention is given to reports that discuss not only the techniques used, but also any results obtained.
Export Options
About this article
Cite this article as:
Miller L. Jennifer, Recent Developments in Focused Library Design: Targeting Gene-Families, Current Topics in Medicinal Chemistry 2006; 6 (1) . https://dx.doi.org/10.2174/156802606775193347
DOI https://dx.doi.org/10.2174/156802606775193347 |
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
-
The Feasibility of Low-dose Chest CT Acquisition Protocol for the Imaging of COVID-19 Pneumonia
Current Medical Imaging RNA Interference-Based Therapeutics: New Strategies to Fight Infectious Disease
Infectious Disorders - Drug Targets Management of Adult Active Tuberculosis Disease in Era of HIV Pandemic, Current Practices and Future Perspectives
Infectious Disorders - Drug Targets Withdrawal Notice: The Water Industry and Decarbonisation of Cities: A Review
Current Environmental Management (Discontinued) Scientific and Clinical Challenges in Sepsis
Current Pharmaceutical Design Microwave Assisted Synthesis, Biological Characterization and Docking Studies of Pyrimidine Derivatives
Current Microwave Chemistry Pharmacological Diversity of Triazole Scaffolds: A Review
Current Bioactive Compounds Subject Index to Volume 10
Current Pharmaceutical Design SNew Trends in the Development of Opioid Peptide Analogues as Advanced Remedies for Pain Relief
Current Topics in Medicinal Chemistry G Protein Coupled Receptors - In Silico Drug Discovery and Design
Current Topics in Medicinal Chemistry A Review on the Role of Transition Metals in Selenylation Reactions
Current Organic Synthesis COVID-19 Pandemic: An Overview of its Origin, Current Status, and Ongoing Clinical Trials
Coronaviruses Thieno[2,3-<i>d</i>]pyrimidin-4(3<i>H</i>)-one Derivatives of Benzimidazole as Potential Anti- Breast Cancer (MDA-MB-231, MCF-7) Agents
Anti-Cancer Agents in Medicinal Chemistry Properties and Architecture of Drugs and Natural Products Revisited
Current Chemical Biology Synthesis and Biological Activity of 2,7-Naphthyridine Derivatives: An Overview
Current Organic Chemistry New Ideas for a 160 Years-Old Reaction
Current Organic Synthesis Generation and Transplantation of Dopaminergic Neurons Derived from Embryonic Stem Cells
Current Stem Cell Research & Therapy Characteristic Peptides of Protein Secondary Structural Motifs
Protein & Peptide Letters Antiobesity Carbonic Anhydrase Inhibitors
Current Topics in Medicinal Chemistry Synthesis and SAR Studies of Antibacterial Peptidyl Derivatives Based upon the Binding Site of Human Cystatin C
Protein & Peptide Letters