LipE guided discovery of isopropylphenyl pyridazines as pantothenate kinase modulators.
Hit-to-lead
Lipophilic ligand efficiency
Pantothenate Kinase
Pyridazine
Journal
Bioorganic & medicinal chemistry
ISSN: 1464-3391
Titre abrégé: Bioorg Med Chem
Pays: England
ID NLM: 9413298
Informations de publication
Date de publication:
15 12 2021
15 12 2021
Historique:
received:
22
08
2021
revised:
20
10
2021
accepted:
02
11
2021
pubmed:
24
11
2021
medline:
19
1
2022
entrez:
23
11
2021
Statut:
ppublish
Résumé
Pantothenate kinase (PANK) is the critical regulator of intracellular levels of coenzyme A and has emerged as an attractive target for treating neurological and metabolic disorders. This report describes the optimization, synthesis, and full structure-activity relationships of a new chemical series of pantothenate competitive PANK inhibitors. Potent drug-like molecules were obtained by optimizing a high throughput screening hit, using lipophilic ligand efficiency (LipE) derived from human PANK3 IC
Identifiants
pubmed: 34814071
pii: S0968-0896(21)00512-5
doi: 10.1016/j.bmc.2021.116504
pmc: PMC8693618
mid: NIHMS1758667
pii:
doi:
Substances chimiques
Ligands
0
Pyridazines
0
Phosphotransferases (Alcohol Group Acceptor)
EC 2.7.1.-
pantothenate kinase
EC 2.7.1.33
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
116504Subventions
Organisme : NCI NIH HHS
ID : P30 CA021765
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM034496
Pays : United States
Organisme : NIGMS NIH HHS
ID : R37 GM034496
Pays : United States
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.
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