[1,2,4]Triazolo[1,5-a]pyrimidine Phosphodiesterase 2A Inhibitors: Structure and Free-Energy Perturbation-Guided Exploration

Autor: Frans A. F. Van den Keybus, Peter Jacobus Johannes Antonius Buijnsters, Andrés A. Trabanco, Marijke Somers, Marieke Lamers, Gary Tresadern, Greet Vanhoof, Yves Emiel Maria Van Roosbroeck, Gregor James Macdonald, Ingrid Velter, Philip Leonard

Publikováno v: Journal of Medicinal Chemistry. 63:12887-12910

We describe the hit-to-lead exploration of a [1,2,4]triazolo[1,5-a]pyrimidine phosphodiesterase 2A (PDE2A) inhibitor arising from high-throughput screening. X-ray crystallography enabled structure-guided design, leading to the identification of prefe

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::e154a70a8fb0c9559794b8e1758a37f4
https://doi.org/10.1021/acs.jmedchem.0c01272

Repurposing High-Throughput Image Assays Enables Biological Activity Prediction for Drug Discovery

Autor: Adam Arany, Jörg K. Wegner, Jorge Vialard, Vladimir Chupakhin, Marvin Steijaert, Anne E. Carpenter, Shantanu Singh, Peter Jacobus Johannes Antonius Buijnsters, Yves Moreau, Jaak Simm, Emmanuel Gustin, Ingrid Velter, Roel Wuyts, Sepp Hochreiter, A. Vapirev, Yolanda T. Chong, Hugo Ceulemans, Günter Klambauer

In both academia and the pharmaceutical industry, large-scale assays for drug discovery are expensive and often impractical, particularly for the increasingly important physiologically relevant model systems that require primary cells, organoids, who

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::afdc9b02e29c077539f5f8d0bd2c0b57
https://lirias.kuleuven.be/handle/123456789/628737

Repurposed high-throughput images enable biological activity prediction for drug discovery

Autor: Jorge Vialard, Vladimir Chupakhin, Yves Moreau, Günter Klambauer, Shantanu Singh, Marvin Steijaert, Adam Arany, Sepp Hochreiter, Anne E. Carpenter, Hugo Ceulemans, Roel Wuyts, Emmanuel Gustin, Jörg K. Wegner, Peter Jacobus Johannes Antonius Buijnsters, A. Vapirev, Ingrid Velter, Jaak Simm, Yolanda T. Chong

We repurpose a High-Throughput (cell) Imaging (HTI) screen of a glucocorticoid receptor assay to predict target protein activity in multiple other seemingly unrelated assays. In two ongoing drug discovery projects, our repurposing approach increased

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0059d469db8ccdab4e892970cfab25d3

Structure-Based Design of a Potent, Selective, and Brain Penetrating PDE2 Inhibitor with Demonstrated Target Engagement

Autor: Andrés A. Trabanco, Meri De Angelis, Peter Jacobus Johannes Antonius Buijnsters, Wendy Sanderson, Alison Ritchie, Greet Vanhoof, Xavier Langlois, Yves Emiel Maria Van Roosbroeck, Gary Tresadern, Frederik J. R. Rombouts, José-Ignacio Andrés

Publikováno v: ACS medicinal chemistry letters. 5(9)

Structure-guided design led to the identification of the novel, potent, and selective phosphodiesterase 2 (PDE2) inhibitor 12. Compound 12 demonstrated a >210-fold selectivity versus PDE10 and PDE11 and was inactive against all other PDE family membe

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c0c2fc29e7e676e20fb45578d45ffa03
https://pubmed.ncbi.nlm.nih.gov/25221665

Assemblies of aziridinemethanols

Autor: Martinus C. Feiters, Nico A. J. M. Sommerdijk, Peter ten Holte, Sandy A. C. Verhaegen, Peter Jacobus Johannes Antonius Buijnsters, Arthur M.A. Pistorius, René de Gelder, Roeland J. M. Nolte, Binne Zwanenburg

Publikováno v: Journal of Materials Chemistry, 11(2), 269-277. Royal Society of Chemistry
Journal of Materials Chemistry, 11, 269-277
Journal of Materials Chemistry, 11, pp. 269-277
Journal of Materials Chemistry, 11, 2, pp. 269-277
Journal of Materials Chemistry, 11, 269-277. Royal soc chemistry

Two novel long chain aziridinemethanols ( 1b, c) are described and their molecular organisation in the bulk and self-assembling properties in aqueous dispersion are reported. The orientation of the NH hydrogen of the aziridinealcohol moiety in 1b can

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8d86c6402eeda10047caba2de64c4ed1
https://doi.org/10.1039/b006428i