ArticleCommunications chemistry2020
Rapid optimisation of fragments and hits to lead compounds from screening of crude reaction mixtures.
Article in Communications chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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Who cites it
13 citing papers in PubMed.
- Syndirella: synthesis-directed fragment elaboration enables extensive and cost-effective binding site exploration beyond catalog compounds.Chemical science · 2026Article
- A resource-efficient structure-based workflow for fragment progression enables parallel hit discovery and validation of functionally diverse modulators of NCS-1 protein-protein interactions.Chemical science · 2026Article
- Accelerate Your Science: Direct-to-Biology Strategies in Medicinal Chemistry.Journal of medicinal chemistry · 2026Review
- Direct-to-Biology: Streamlining the Path From Chemistry to Biology in Drug Discovery.ChemMedChem · 2026Review
- Developments and challenges in hit progression within fragment-based drug discovery.Nature communications · 2026Review
- Advancing Medicinal Chemistry Through FMO: Sygnature's Platform.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Binding-Site Purification of Actives (B-SPA) Enables Efficient Large-Scale Progression of Fragment Hits by Combining Multi-Step Array Synthesis With HT Crystallography.Angewandte Chemie (International ed. in English) · 2025Article
- Targeting HIV-1 Reverse Transcriptase Using a Fragment-Based Approach.Molecules (Basel, Switzerland) · 2023Article
- Discovery of the 3-Amino-1,2,4-triazine-Based Library as Selective PDK1 Inhibitors with Therapeutic Potential in Highly Aggressive Pancreatic Ductal Adenocarcinoma.International journal of molecular sciences · 2023Article
- Fragment-based drug discovery-the importance of high-quality molecule libraries.Molecular oncology · 2022Review
- Fragment-to-Lead Medicinal Chemistry Publications in 2020.Journal of medicinal chemistry · 2022Review
- Frag4Lead: growing crystallographic fragment hits by catalog using fragment-guided template docking.Acta crystallographica. Section D, Structural biology · 2021Article
- Combining generative artificial intelligence and on-chip synthesis for de novo drug design.Science advances · 2021Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Fragment based methods are now widely used to identify starting points in drug discovery and generation of tools for chemical biology. A significant challenge is optimization of these weak binding fragments to hit and lead compounds. We have developed an approach where individual reaction mixtures of analogues of hits can be evaluated without purification of the product. Here, we describe experiments to optimise the processes and then assess such mixtures in the high throughput crystal structure determination facility, XChem. Diffraction data for crystals of the proteins Hsp90 and PDHK2 soaked individually with 83 crude reaction mixtures are analysed manually or with the automated XChem procedures. The results of structural analysis are compared with binding measurements from other biophysical techniques. This approach can transform early hit to lead optimisation and the lessons learnt from this study provide a protocol that can be used by the community.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.