Abstract
The chemical space is so vast that only a small portion of it has been examined. As a complementary approach to systematically probe the chemical space, virtual combinatorial library design has extended enormous impacts on generating novel and diverse structures for drug discovery. Despite the favorable contributions, high attrition rates in drug development that mainly resulted from lack of efficacy and side effects make it increasingly challenging to discover good chemical starting points. In most cases, focused libraries, which are restricted to particular regions of the chemical space, are deftly exploited to maximize hit rate and improve efficiency at the beginning of the drug discovery and drug development pipeline. This paper presented a valid methodology for fast target-focused combinatorial library design in both reaction-based and production-based ways with the library creating rates of approximately 70,000 molecules per second. Simple, quick and convenient operating procedures are the specific features of the method. SHAFTS, a hybrid 3D similarity calculation software, was embedded to help refine the size of the libraries and improve hit rates. Two target-focused (p38-focused and COX2-focused) libraries were constructed efficiently in this study. This rapid library enumeration method is portable and applicable to any other targets for good chemical starting points identification collaborated with either structure-based or ligand-based virtual screening.
Keywords: 3D molecular similarity, chemical space, focused library design, product-based, reaction-based, SMILES.
Combinatorial Chemistry & High Throughput Screening
Title:A Rapid Python-Based Methodology for Target-Focused Combinatorial Library Design
Volume: 19 Issue: 1
Author(s): Shiliang Li, Yuwei Song, Xiaofeng Liu and Honglin Li
Affiliation:
Keywords: 3D molecular similarity, chemical space, focused library design, product-based, reaction-based, SMILES.
Abstract: The chemical space is so vast that only a small portion of it has been examined. As a complementary approach to systematically probe the chemical space, virtual combinatorial library design has extended enormous impacts on generating novel and diverse structures for drug discovery. Despite the favorable contributions, high attrition rates in drug development that mainly resulted from lack of efficacy and side effects make it increasingly challenging to discover good chemical starting points. In most cases, focused libraries, which are restricted to particular regions of the chemical space, are deftly exploited to maximize hit rate and improve efficiency at the beginning of the drug discovery and drug development pipeline. This paper presented a valid methodology for fast target-focused combinatorial library design in both reaction-based and production-based ways with the library creating rates of approximately 70,000 molecules per second. Simple, quick and convenient operating procedures are the specific features of the method. SHAFTS, a hybrid 3D similarity calculation software, was embedded to help refine the size of the libraries and improve hit rates. Two target-focused (p38-focused and COX2-focused) libraries were constructed efficiently in this study. This rapid library enumeration method is portable and applicable to any other targets for good chemical starting points identification collaborated with either structure-based or ligand-based virtual screening.
Export Options
About this article
Cite this article as:
Li Shiliang, Song Yuwei, Liu Xiaofeng and Li Honglin, A Rapid Python-Based Methodology for Target-Focused Combinatorial Library Design, Combinatorial Chemistry & High Throughput Screening 2016; 19 (1) . https://dx.doi.org/10.2174/1386207318666151102094055
DOI https://dx.doi.org/10.2174/1386207318666151102094055 |
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
-
Correlates of Immune Protection from Tuberculosis
Current Molecular Medicine Cell Death Targeting Therapies in B Lymphoid Malignancies
Current Drug Targets RNA Therapeutics Directed to the Non Coding Regions of APP mRNA, In Vivo Anti-Amyloid Efficacy of Paroxetine, Erythromycin, and N-acetyl cysteine
Current Alzheimer Research Hyaluronic Acid as a Protein Polymeric Carrier: An Overview and a Report on Human Growth Hormone
Current Drug Targets Disorders of Respiration and Sleep-Disordered Breathing in Patients with Chronic Renal Failure
Current Respiratory Medicine Reviews Inhibition of Type 1 Diabetes Development by Vitamin D Receptor Agonists
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Ledipasvir/Sofosbuvir versus Daclatasvir/Sofosbuvir for the Treatment of Chronic Hepatitis C Genotype 4 Patients
Current Drug Safety Immune Checkpoint Inhibitors in AML-A New Frontier
Current Cancer Drug Targets β-Glucans: Old Molecules with Newly Discovered Immunological Activities
Drug Design Reviews - Online (Discontinued) Treating Chronic Hepatitis B: Today and Tomorrow
Current Medicinal Chemistry Exploiting Cyclooxygenase-(in)Dependent Properties of COX-2 Inhibitors for Malignant Glioma Therapy
Anti-Cancer Agents in Medicinal Chemistry Astrocyte Pathology in Major Depressive Disorder: Insights from Human Postmortem Brain Tissue
Current Drug Targets Functional Roles of the Ca2+-activated K+ Channel, KCa3.1, in Brain Tumors
Current Neuropharmacology The Relationship of Developmental Changes in White Matter to the Onset of Psychosis
Current Pharmaceutical Design Generation of Redox Imbalance Mediates the Cytotoxic Effect of Malabaricone-A in a Multidrug Resistant Cell Line
Anti-Cancer Agents in Medicinal Chemistry New Aspects in Sustained Drug Release Formulations
Recent Patents on Drug Delivery & Formulation Pharmacogenetics in Geriatric Medicine: Challenges and Opportunities for Clinical Practice
Current Drug Metabolism Leptin, Estrogens and Cancer
Mini-Reviews in Medicinal Chemistry Inflammation as a Therapeutic Target in Acute Ischemic Stroke Treatment
Current Topics in Medicinal Chemistry Immunophilin Chaperones in Steroid Receptor Signalling
Current Topics in Medicinal Chemistry