AI Article Synopsis
- The study evaluates the effectiveness of six types of 2D fingerprints for scaffold hopping in drug discovery.
- It finds that 2D fingerprints can successfully identify new scaffolds, with varying success based on the diversity of tested compounds.
- The extended connectivity fingerprint (ECFP4) is particularly effective for this purpose, highlighting the usefulness of 2D fingerprints in lead discovery.
Article Abstract
Background: It has been suggested that similarity searching using 2D fingerprints may not be suitable for scaffold hopping.
Methods: This article reports a detailed evaluation of the effectiveness of six common types of 2D fingerprints when they are used for scaffold-hopping similarity searches of the Molecular Design Limited Drug Data Report database, World of Molecular Bioactivity database and Maximum Unbiased Validation database.
Results: The results demonstrate that 2D fingerprints can be used for scaffold hopping, with novel scaffolds being identified in nearly every search that was carried out. The degree of enrichment depends on the structural diversity of the actives that are being sought, with the greatest enrichments often being obtained using the extended connectivity fingerprint encoding a circular substructure of diameter four bonds (ECFP4) fingerprint.
Conclusion: 2D fingerprints provide a simple and computationally efficient way of identifying novel chemotypes in lead-discovery programs.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.4155/fmc.11.4 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Novel sigma 1-antagonists with -(+)-normetazocine scaffold: synthesis, molecular modeling, and antinociceptive effect.
RSC Med Chem
November 2024
Department of Drug and Health Sciences, University of Catania Viale A. Doria 6 95125 Catania Italy (+39) 095 7384273.
Inflammatory pain represents one of the unmet clinical needs for patients, as conventional therapies cause several side effects. Recently, new targets involved in inflammatory pain modulation have been identified, including the sigma-1 receptor (σ1R). Selective σ1R antagonists have demonstrated analgesic efficacy in acute and chronic inflammatory pain models.
View Article and Find Full Text PDF3D printed sodium Alginate-Gelatin hydrogel loaded with Santalum album oil as an antibacterial Full-Thickness wound healing and scar reduction Scaffold: In vitro and in vivo study.
Int J Pharm
January 2025
Department of Stem Cells and Regenerative Medicine, D. Y. Patil Education Society (Deemed to be University), Kolhapur 416006, India. Electronic address:
Managing wounds and accompanying consequences like exudation and microbiological infections is challenging in clinical practice. Bioactive compounds from traditional medicinal plants help heal wounds, although their bioavailability is low. This study uses sodium alginate (SA), gelatin (G), and Santalum album oil (SAL) to 3D print a polymeric hydrogel scaffold to circumvent these difficulties.
View Article and Find Full Text PDFIdentification and structural characterization of CB1 receptor antagonists: A comprehensive virtual screening and molecular dynamics study of arachidin-2.
Biophys Chem
December 2024
Tecnologico de Monterrey, The Institute for Obesity Research, Unit of Experimental Medicine, Monterrey, NL 64849, Mexico. Electronic address:
The cannabinoid receptor 1 (CB1) is an essential component of the endocannabinoid system, responsible for regulating various physiological processes such as pain, mood, and appetite. Despite increasing interest in the therapeutic potential of CB1 modulators, the precise mechanisms by which small molecules modulate receptor activity-particularly without fully transitioning between active and inactive states-remain partially understood. In this study, the complexity of CB1-ligand interactions was evaluated for the inactive CB1 state.
View Article and Find Full Text PDFNitrogen-containing heterocycles as important scaffold for selective and potent HDAC8 inhibition: a step towards effective, non-toxic and selective HDAC8 inhibitor discovery.
J Biomol Struct Dyn
December 2024
Laboratory of Drug Design and Discovery, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.
Selective inhibition of histone deacetylase 8 (HDAC8) has emerged as a promising approach for treating various diseases, including cancer. However, finding key structural features for HDAC8 inhibition and developing effective and selective HDAC8 inhibitors (HDAC8s) pose significant challenges. In the past few years, the development of various scaffolds for inhibiting HDAC8 has significantly risen and the quest continues.
View Article and Find Full Text PDFCombining crystallographic and binding affinity data towards a novel dataset of small molecule overlays.
J Comput Aided Mol Des
December 2024
University of Hamburg, ZBH - Center for Bioinformatics, Albert-Einstein-Ring 8-10, 22761, Hamburg, Germany.
Although small molecule superposition is a standard technique in drug discovery, a rigorous performance assessment of the corresponding methods is currently challenging. Datasets in this field are sparse, small, tailored to specific applications, unavailable, or outdated. The newly developed LOBSTER set described herein offers a publicly available and method-independent dataset for benchmarking and method optimization.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!