Targeting ALK2: An Open Science Approach to Developing Therapeutics for the Treatment of Diffuse Intrinsic Pontine Glioma.
Activin Receptors, Type I
/ antagonists & inhibitors
Animals
Benzamides
/ chemical synthesis
Caco-2 Cells
Cell Membrane Permeability
/ drug effects
Diffuse Intrinsic Pontine Glioma
/ drug therapy
Female
HEK293 Cells
Humans
Male
Mice, SCID
Microsomes, Liver
/ metabolism
Molecular Structure
Mutation
Piperazines
/ chemical synthesis
Protein Kinase Inhibitors
/ chemical synthesis
Pyridines
/ chemical synthesis
Structure-Activity Relationship
Journal
Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531
Informations de publication
Date de publication:
14 05 2020
14 05 2020
Historique:
pubmed:
6
5
2020
medline:
3
11
2020
entrez:
6
5
2020
Statut:
ppublish
Résumé
Diffuse intrinsic pontine glioma is an aggressive pediatric cancer for which no effective chemotherapeutic drugs exist. Analysis of the genomic landscape of this disease has led to the identification of the serine/threonine kinase ALK2 as a potential target for therapeutic intervention. In this work, we adopted an open science approach to develop a series of potent type I inhibitors of ALK2 which are orally bio-available and brain-penetrant. Initial efforts resulted in the discovery of
Identifiants
pubmed: 32369358
doi: 10.1021/acs.jmedchem.0c00395
pmc: PMC8213057
doi:
Substances chimiques
Benzamides
0
Piperazines
0
Protein Kinase Inhibitors
0
Pyridines
0
ACVR1 protein, human
EC 2.7.11.30
Activin Receptors, Type I
EC 2.7.11.30
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4978-4996Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 106169/ZZ14/Z
Pays : United Kingdom
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