Using Fragment-Based Approaches to Discover New Antibiotics

Overview

Journal SLAS Discov

Publisher Sage Publications

Specialty Molecular Biology

Date 2018 Jun 21

PMID 29923463

Citations 9

Authors

Bas Lamoree

Roderick E Hubbard

Affiliations

Soon will be listed here.

Abstract

Fragment-based lead discovery has emerged over the past two decades as a successful approach to generate novel lead candidates in drug discovery programs. The two main advantages over conventional high-throughput screening (HTS) are more efficient sampling of chemical space and tighter control over the physicochemical properties of the lead candidates. Antibiotics are a class of drugs with particularly strict property requirements for efficacy and safety. The development of novel antibiotics has slowed down so much that resistance has now evolved against every available antibiotic drug. Here we give an overview of fragment-based approaches in screening and lead discovery projects for new antibiotics. We discuss several successful hit-to-lead development examples. Finally, we highlight the current challenges and opportunities for fragment-based lead discovery toward new antibiotics.

Citing Articles

High-Throughput Screening of Natural Product and Synthetic Molecule Libraries for Antibacterial Drug Discovery.

Ayon N Metabolites. 2023; 13(5).

PMID: 37233666 PMC: 10220967. DOI: 10.3390/metabo13050625.

Fragment-Based Lead Discovery Strategies in Antimicrobial Drug Discovery.

Konaklieva M, Plotkin B Antibiotics (Basel). 2023; 12(2).

PMID: 36830226 PMC: 9951956. DOI: 10.3390/antibiotics12020315.

Pathogen-associated gene discovery workflows for novel antivirulence therapeutic development.

Lau W, Taylor P, Brinkman F, Lee A EBioMedicine. 2023; 88:104429.

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Discovery of a fragment hit compound targeting D-Ala:D-Ala ligase of bacterial peptidoglycan biosynthesis.

Proj M, Hrast M, Bajc G, Frlan R, Meden A, Butala M J Enzyme Inhib Med Chem. 2022; 38(1):387-397.

PMID: 36446617 PMC: 9718554. DOI: 10.1080/14756366.2022.2149745.

Implications of Fragment-Based Drug Discovery in Tuberculosis and HIV.

Mallakuntla M, Togre N, Santos D, Tiwari S Pharmaceuticals (Basel). 2022; 15(11).

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