Xavier Barril
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View article: Water Networks as Hydrophobic Recognition Motifs in Proteins
Water Networks as Hydrophobic Recognition Motifs in Proteins Open
The hydrophobic effect is a central force in molecular recognition, typically attributed to the ordering of water molecules around apolar groups. Hydrophobic interaction sites on proteins are therefore readily predicted based on surface po…
View article: Water Networks as Hydrophobic Recognition Motifs in Proteins
Water Networks as Hydrophobic Recognition Motifs in Proteins Open
The hydrophobic effect is a central force in molecular recognition, typically attributed to the ordering of water molecules around apolar groups. Hydrophobic interaction sites on proteins are therefore readily predicted based on surface po…
View article: Discovering Uncharted Binding Pockets on E3 Ligases Leads to the Identification of FBW7 Allosteric Modulators
Discovering Uncharted Binding Pockets on E3 Ligases Leads to the Identification of FBW7 Allosteric Modulators Open
E3 ligases are key regulators of the ubiquitin‐proteasome system (UPS) and have emerged as attractive drug target candidates for precise therapeutic intervention. Additionally, their ligands are extremely valuable as handles for Targeted P…
View article: A bottom-up approach to find lead compounds in expansive chemical spaces
A bottom-up approach to find lead compounds in expansive chemical spaces Open
Drug discovery starts with the identification of a “hit” compound that, following a long and expensive optimization process, evolves into a drug candidate. Bigger screening collections increase the odds of finding more and better hits. For…
View article: The Quasi-Bound State as a Predictor of Relative Binding Free Energy
The Quasi-Bound State as a Predictor of Relative Binding Free Energy Open
Relative binding free energy (ΔΔGbind) predictions have become the main approach to evaluate the potency of a congeneric series of compounds. They are enabled by alchemical transformations coupled to free energy methods, tools that have be…
View article: The Quasi-bound State as a Predictor of Relative Binding Free Energy
The Quasi-bound State as a Predictor of Relative Binding Free Energy Open
Relative binding free energy (ΔΔGbind) predictions have become the main approach to evaluate the potency of a congeneric series of compounds. They are enabled by alchemical transformations coupled to free energy methods, tools that have be…
View article: Integrated computational and biosensor-based strategies for the discovery of allosteric SMYD3 ligands using diperodon as a starting point
Integrated computational and biosensor-based strategies for the discovery of allosteric SMYD3 ligands using diperodon as a starting point Open
SMYD3 (SET- and MYND-domain containing protein 3) is an epigenetic enzyme with lysine methyl transferase activity and multiple protein binding partners. It is implicated in cancer development and active site inhibitors with antitumor activ…
View article: The Quasi-bound State as a Predictor of Relative Binding Free Energy
The Quasi-bound State as a Predictor of Relative Binding Free Energy Open
Relative binding free energy (ΔΔGbind) predictions have become the main approach to evaluate the potency of a congeneric series of compounds. They are enabled by alchemical transformations coupled to free energy methods, tools that have be…
View article: A novel bottom-up approach to find lead-compounds in billion-sized libraries
A novel bottom-up approach to find lead-compounds in billion-sized libraries Open
Drug discovery starts with the identification of a ‘hit’ compound that, following a long and expensive optimization process, evolves into a drug candidate. Bigger screening collections increase the odds of finding more and better hits. For…
View article: Syntheses of differentially fluorinated triazole-based 1-deoxysphingosine analogues <i>en route</i> to SphK inhibitors
Syntheses of differentially fluorinated triazole-based 1-deoxysphingosine analogues <i>en route</i> to SphK inhibitors Open
Stereoselective syntheses of 16 triazole-based 1-deoxysphingosine dual SphK inhibitors incorporating different systematic modifications highlight heptafluoropropyl and guanidinium motifs towards improving SphK2 inhibition.
View article: Use of the Novel Site-Directed Enzyme Enhancement Therapy (SEE-Tx) Drug Discovery Platform to Identify Pharmacological Chaperones for Glutaric Acidemia Type 1
Use of the Novel Site-Directed Enzyme Enhancement Therapy (SEE-Tx) Drug Discovery Platform to Identify Pharmacological Chaperones for Glutaric Acidemia Type 1 Open
Allosteric regulators acting as pharmacological chaperones hold promise for innovative therapeutics since they target noncatalytic sites and stabilize the folded protein without competing with the natural substrate, resulting in a net gain…
View article: Comprehensive detection and characterization of human druggable pockets through binding site descriptors
Comprehensive detection and characterization of human druggable pockets through binding site descriptors Open
Druggable pockets are protein regions that have the ability to bind organic small molecules, and their characterization is essential in target-based drug discovery. However, deriving pocket descriptors is challenging and existing strategie…
View article: The Role of Water Networks in Phosphodiesterase Inhibitor Dissociation and Kinetic Selectivity
The Role of Water Networks in Phosphodiesterase Inhibitor Dissociation and Kinetic Selectivity Open
In search of new opportunities to develop Trypanosoma brucei phosphodiesterase B1 (TbrPDEB1) inhibitors that have selectivity over the off‐target human PDE4 (hPDE4), different stages of a fragment‐growing campaign were studied using a vari…
View article: Discovery of allosteric regulators with clinical potential to stabilize alpha-L-iduronidase in mucopolysaccharidosis type I
Discovery of allosteric regulators with clinical potential to stabilize alpha-L-iduronidase in mucopolysaccharidosis type I Open
Mucopolysaccharidosis type I (MPS I) is an inherited lysosomal disease caused by lowered activity of the enzyme alpha-L-iduronidase (IDUA). Current therapeutic options show limited efficacy and do not treat some important aspects of the di…
View article: Comprehensive detection and characterization of human druggable pockets through novel binding site descriptors
Comprehensive detection and characterization of human druggable pockets through novel binding site descriptors Open
Druggable pockets are protein regions that have the ability to bind organic small molecules, and their characterization is essential in target-based drug discovery. However, strategies to derive pocket descriptors are scarce and usually ex…
View article: Validation of a highly sensitive HaloTag-based assay to evaluate the potency of a novel class of allosteric β-Galactosidase correctors
Validation of a highly sensitive HaloTag-based assay to evaluate the potency of a novel class of allosteric β-Galactosidase correctors Open
Site-directed Enzyme Enhancement Therapy (SEE-Tx®) technology is a disease-agnostic drug discovery tool that can be applied to any protein target of interest with a known three-dimensional structure. We used this proprietary technology to …
View article: Multi-Responsive Eight-State Bis(acridinium-Zn(II) porphyrin) Receptor
Multi-Responsive Eight-State Bis(acridinium-Zn(II) porphyrin) Receptor Open
A multi-responsive receptor consisting of two (acridinium-Zn(II) porphyrin) conjugates has been designed. The binding constant between this receptor and a ditopic guest has been modulated (i) upon addition of nucleophiles converting acridi…
View article: Lenalidomide Stabilizes Protein–Protein Complexes by Turning Labile Intermolecular H-Bonds into Robust Interactions
Lenalidomide Stabilizes Protein–Protein Complexes by Turning Labile Intermolecular H-Bonds into Robust Interactions Open
Targeted protein degradation is a promising therapeutic strategy, spearheaded by the anti-myeloma drugs lenalidomide and pomalidomide. These drugs stabilize very efficiently the complex between the E3 ligase Cereblon (CRBN) and several non…
View article: Data from Inhibition of the heat shock protein 90 molecular chaperone <i>in vitro</i> and <i>in vivo</i> by novel, synthetic, potent resorcinylic pyrazole/isoxazole amide analogues
Data from Inhibition of the heat shock protein 90 molecular chaperone <i>in vitro</i> and <i>in vivo</i> by novel, synthetic, potent resorcinylic pyrazole/isoxazole amide analogues Open
Although the heat shock protein 90 (HSP90) inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) shows clinical promise, potential limitations encourage development of alternative chemotypes. We discovered the 3,4-diarylpyrazole resorc…
View article: Adobe PDF - MCT-07-0149--Suppl_Data.pdf from Inhibition of the heat shock protein 90 molecular chaperone <i>in vitro</i> and <i>in vivo</i> by novel, synthetic, potent resorcinylic pyrazole/isoxazole amide analogues
Adobe PDF - MCT-07-0149--Suppl_Data.pdf from Inhibition of the heat shock protein 90 molecular chaperone <i>in vitro</i> and <i>in vivo</i> by novel, synthetic, potent resorcinylic pyrazole/isoxazole amide analogues Open
Adobe PDF - MCT-07-0149--Suppl_Data.pdf from Inhibition of the heat shock protein 90 molecular chaperone in vitro and in vivo by novel, synthetic, potent resorcinylic pyrazole/isoxazole amide analogues
View article: Adobe PDF - MCT-07-0149--Suppl_Data.pdf from Inhibition of the heat shock protein 90 molecular chaperone <i>in vitro</i> and <i>in vivo</i> by novel, synthetic, potent resorcinylic pyrazole/isoxazole amide analogues
Adobe PDF - MCT-07-0149--Suppl_Data.pdf from Inhibition of the heat shock protein 90 molecular chaperone <i>in vitro</i> and <i>in vivo</i> by novel, synthetic, potent resorcinylic pyrazole/isoxazole amide analogues Open
Adobe PDF - MCT-07-0149--Suppl_Data.pdf from Inhibition of the heat shock protein 90 molecular chaperone in vitro and in vivo by novel, synthetic, potent resorcinylic pyrazole/isoxazole amide analogues
View article: Data from Inhibition of the heat shock protein 90 molecular chaperone <i>in vitro</i> and <i>in vivo</i> by novel, synthetic, potent resorcinylic pyrazole/isoxazole amide analogues
Data from Inhibition of the heat shock protein 90 molecular chaperone <i>in vitro</i> and <i>in vivo</i> by novel, synthetic, potent resorcinylic pyrazole/isoxazole amide analogues Open
Although the heat shock protein 90 (HSP90) inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) shows clinical promise, potential limitations encourage development of alternative chemotypes. We discovered the 3,4-diarylpyrazole resorc…
View article: Supplementary Figure 5A-B from NVP-AUY922: A Novel Heat Shock Protein 90 Inhibitor Active against Xenograft Tumor Growth, Angiogenesis, and Metastasis
Supplementary Figure 5A-B from NVP-AUY922: A Novel Heat Shock Protein 90 Inhibitor Active against Xenograft Tumor Growth, Angiogenesis, and Metastasis Open
Supplementary Figure 5A-B from NVP-AUY922: A Novel Heat Shock Protein 90 Inhibitor Active against Xenograft Tumor Growth, Angiogenesis, and Metastasis
View article: Supplementary Figures 1A-B from NVP-AUY922: A Novel Heat Shock Protein 90 Inhibitor Active against Xenograft Tumor Growth, Angiogenesis, and Metastasis
Supplementary Figures 1A-B from NVP-AUY922: A Novel Heat Shock Protein 90 Inhibitor Active against Xenograft Tumor Growth, Angiogenesis, and Metastasis Open
Supplementary Figures 1A-B from NVP-AUY922: A Novel Heat Shock Protein 90 Inhibitor Active against Xenograft Tumor Growth, Angiogenesis, and Metastasis
View article: Supplementary Figure 3A-B from NVP-AUY922: A Novel Heat Shock Protein 90 Inhibitor Active against Xenograft Tumor Growth, Angiogenesis, and Metastasis
Supplementary Figure 3A-B from NVP-AUY922: A Novel Heat Shock Protein 90 Inhibitor Active against Xenograft Tumor Growth, Angiogenesis, and Metastasis Open
Supplementary Figure 3A-B from NVP-AUY922: A Novel Heat Shock Protein 90 Inhibitor Active against Xenograft Tumor Growth, Angiogenesis, and Metastasis
View article: Supplementary Figure 2 from NVP-AUY922: A Novel Heat Shock Protein 90 Inhibitor Active against Xenograft Tumor Growth, Angiogenesis, and Metastasis
Supplementary Figure 2 from NVP-AUY922: A Novel Heat Shock Protein 90 Inhibitor Active against Xenograft Tumor Growth, Angiogenesis, and Metastasis Open
Supplementary Figure 2 from NVP-AUY922: A Novel Heat Shock Protein 90 Inhibitor Active against Xenograft Tumor Growth, Angiogenesis, and Metastasis
View article: Supplementary Figure 5C-D from NVP-AUY922: A Novel Heat Shock Protein 90 Inhibitor Active against Xenograft Tumor Growth, Angiogenesis, and Metastasis
Supplementary Figure 5C-D from NVP-AUY922: A Novel Heat Shock Protein 90 Inhibitor Active against Xenograft Tumor Growth, Angiogenesis, and Metastasis Open
Supplementary Figure 5C-D from NVP-AUY922: A Novel Heat Shock Protein 90 Inhibitor Active against Xenograft Tumor Growth, Angiogenesis, and Metastasis
View article: Supplementary Figure 1C from NVP-AUY922: A Novel Heat Shock Protein 90 Inhibitor Active against Xenograft Tumor Growth, Angiogenesis, and Metastasis
Supplementary Figure 1C from NVP-AUY922: A Novel Heat Shock Protein 90 Inhibitor Active against Xenograft Tumor Growth, Angiogenesis, and Metastasis Open
Supplementary Figure 1C from NVP-AUY922: A Novel Heat Shock Protein 90 Inhibitor Active against Xenograft Tumor Growth, Angiogenesis, and Metastasis
View article: Supplementary Figure 4A-B from NVP-AUY922: A Novel Heat Shock Protein 90 Inhibitor Active against Xenograft Tumor Growth, Angiogenesis, and Metastasis
Supplementary Figure 4A-B from NVP-AUY922: A Novel Heat Shock Protein 90 Inhibitor Active against Xenograft Tumor Growth, Angiogenesis, and Metastasis Open
Supplementary Figure 4A-B from NVP-AUY922: A Novel Heat Shock Protein 90 Inhibitor Active against Xenograft Tumor Growth, Angiogenesis, and Metastasis