This disclosure features chemical entities (e.g., a compound or a pharmaceutically acceptable salt thereof) that degrades Proto-oncogene VAV 1 protein (VAV1). The chemical entities are useful, e.g., for treating a subject (e.g., a human subject) having an inflammatory or autoimmune disorder.
[EN] PYRIDINAMINE DERIVATIVES AND THEIR USE AS POTASSIUM CHANNEL MODULATORS<br/>[FR] DÉRIVÉS DE PYRIDINAMINE ET LEUR UTILISATION EN TANT QUE MODULATEURS DES CANAUX POTASSIQUES
申请人:[en]XENON PHARMACEUTICALS INC.
公开号:WO2023239729A1
公开(公告)日:2023-12-14
The present disclosure is directed to compounds of Formula (I): wherein m, n, Y, R1, R2, R3, R4and R5are each as described herein, as stereoisomers, enantiomers or tautomers thereof or mixtures thereof; or pharmaceutically acceptable salts, solvates or prodrugs thereof, and pharmaceutical compositions comprising the compounds of Formula (I), as described herein, which are useful as voltage-gated potassium channel modulators and are therefore are useful in treating seizure disorders such as epilepsy.
[EN] PLASMA KALLIKREIN INHIBITORS<br/>[FR] INHIBITEURS DE LA KALLICRÉINE PLASMATIQUE
申请人:[en]MERCK SHARP & DOHME LLC
公开号:WO2023146809A1
公开(公告)日:2023-08-03
The present invention provides a compound of Formula (I) and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing one or more disease states that could benefit from inhibition of plasma kallikrein, including hereditary angioedema, uveitis, posterior uveitis, wet age-related macular degeneration, diabetic macular edema, diabetic retinopathy and retinal vein occlusion. The compounds are selective inhibitors of plasma kallikrein.
Structure-Based Design of Potent and Orally Active Isoindolinone Inhibitors of MDM2-p53 Protein–Protein Interaction
作者:Gianni Chessari、Ian R. Hardcastle、Jong Sook Ahn、Burcu Anil、Elizabeth Anscombe、Ruth H. Bawn、Luke D. Bevan、Timothy J. Blackburn、Ildiko Buck、Celine Cano、Benoit Carbain、Juan Castro、Ben Cons、Sarah J. Cully、Jane A. Endicott、Lynsey Fazal、Bernard T. Golding、Roger J. Griffin、Karen Haggerty、Suzannah J. Harnor、Keisha Hearn、Stephen Hobson、Rhian S. Holvey、Steven Howard、Claire E. Jennings、Christopher N. Johnson、John Lunec、Duncan C. Miller、David R. Newell、Martin E. M. Noble、Judith Reeks、Charlotte H. Revill、Christiane Riedinger、Jeffrey D. St. Denis、Emiliano Tamanini、Huw Thomas、Neil T. Thompson、Mladen Vinković、Stephen R. Wedge、Pamela A. Williams、Nicola E. Wilsher、Bian Zhang、Yan Zhao
DOI:10.1021/acs.jmedchem.0c02188
日期:2021.4.8
(MDM2)-p53 protein–proteininteraction with small molecules has been shown to reactivate p53 and inhibit tumor growth. Here, we describe rational, structure-guided, design of novel isoindolinone-based MDM2 inhibitors. MDM2 X-ray crystallography, quantum mechanics ligand-based design, and metabolite identification all contributed toward the discovery of potent in vitro and in vivo inhibitors of the MDM2-p53