Benjamin D. Cons
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View article: Integrating fragment-based screening with targeted protein degradation and genetic rescue to explore eIF4E function
Integrating fragment-based screening with targeted protein degradation and genetic rescue to explore eIF4E function Open
Eukaryotic initiation factor 4E (eIF4E) serves as a regulatory hub for oncogene-driven protein synthesis and is considered a promising anticancer target. Here we screen a fragment library against eIF4E and identify a ligand-binding site wi…
View article: Fragment-Based Discovery of a Series of Allosteric-Binding Site Modulators of β-Glucocerebrosidase
Fragment-Based Discovery of a Series of Allosteric-Binding Site Modulators of β-Glucocerebrosidase Open
β-Glucocerebrosidase (GBA/GCase) mutations leading to misfolded protein cause Gaucher's disease and are a major genetic risk factor for Parkinson's disease and dementia with Lewy bodies. The identification of small molecule pharmacological…
View article: Alkene 1,3‐Difluorination via Transient Oxonium Intermediates
Alkene 1,3‐Difluorination via Transient Oxonium Intermediates Open
The 1,3‐difunctionalization of unactivated alkenes is an under‐explored transformation that leads to moieties that are otherwise challenging to prepare. Herein, we report a hypervalent iodine‐mediated 1,3‐difluorination of homoallylic (ary…
View article: Alkene 1,3‐Difluorination via Transient Oxonium Intermediates
Alkene 1,3‐Difluorination via Transient Oxonium Intermediates Open
The 1,3‐difunctionalization of unactivated alkenes is an under‐explored transformation that leads to moieties that are otherwise challenging to prepare. Herein, we report a hypervalent iodine‐mediated 1,3‐difluorination of homoallylic (ary…
View article: Enabling synthesis in fragment-based drug discovery (FBDD): microscale high-throughput optimisation of the medicinal chemist's toolbox reactions
Enabling synthesis in fragment-based drug discovery (FBDD): microscale high-throughput optimisation of the medicinal chemist's toolbox reactions Open
Democratised high-throughput experimentation for FBDD.
View article: X-ray Screening of an Electrophilic Fragment Library and Application toward the Development of a Novel ERK 1/2 Covalent Inhibitor
X-ray Screening of an Electrophilic Fragment Library and Application toward the Development of a Novel ERK 1/2 Covalent Inhibitor Open
Fragment-based drug discovery (FBDD) has become an established method for the identification of efficient starting points for drug discovery programs. In recent years, electrophilic fragment screening has garnered increased attention from …
View article: Fragment-Based Discovery of a Novel, Brain Penetrant, Orally Active HDAC2 Inhibitor
Fragment-Based Discovery of a Novel, Brain Penetrant, Orally Active HDAC2 Inhibitor Open
Fragment-based ligand discovery was successfully applied to histone deacetylase HDAC2. In addition to the anticipated hydroxamic acid- and benzamide-based fragment screening hits, a low affinity (∼1 mM) α-amino-amide zinc binding fragment …
View article: Electrostatic Complementarity in Structure-Based Drug Design
Electrostatic Complementarity in Structure-Based Drug Design Open
Optimization of electrostatic complementarity is an important strategy in structure-based drug discovery for improving the affinity of molecules against a specific protein target. In this Miniperspective we identify examples where delibera…