Kinetic and structural investigations of novel inhibitors of human epithelial 15-lipoxygenase-2.
Cellular activity
Computational docking
Crystallography
Enzymology
Hydrogen-deuterium exchange
Inhibitor
Mixed inhibition
lipoxygenase
Journal
Bioorganic & medicinal chemistry
ISSN: 1464-3391
Titre abrégé: Bioorg Med Chem
Pays: England
ID NLM: 9413298
Informations de publication
Date de publication:
15 09 2021
15 09 2021
Historique:
received:
26
05
2021
revised:
27
07
2021
accepted:
30
07
2021
pubmed:
10
9
2021
medline:
31
12
2021
entrez:
9
9
2021
Statut:
ppublish
Résumé
Human epithelial 15-lipoxygenase-2 (h15-LOX-2, ALOX15B) is expressed in many tissues and has been implicated in atherosclerosis, cystic fibrosis and ferroptosis. However, there are few reported potent/selective inhibitors that are active ex vivo. In the current work, we report newly discovered molecules that are more potent and structurally distinct from our previous inhibitors, MLS000545091 and MLS000536924 (Jameson et al, PLoS One, 2014, 9, e104094), in that they contain a central imidazole ring, which is substituted at the 1-position with a phenyl moiety and with a benzylthio moiety at the 2-position. The initial three molecules were mixed-type, non-reductive inhibitors, with IC
Identifiants
pubmed: 34500187
pii: S0968-0896(21)00357-6
doi: 10.1016/j.bmc.2021.116349
pmc: PMC8785688
mid: NIHMS1767811
pii:
doi:
Substances chimiques
Lipoxygenase Inhibitors
0
ALOX15B protein, human
EC 1.13.11.33
Arachidonate 15-Lipoxygenase
EC 1.13.11.33
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
116349Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL107887
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM105671
Pays : United States
Organisme : NIH HHS
ID : S10 OD021527
Pays : United States
Organisme : NIMH NIH HHS
ID : R03 MH081283
Pays : United States
Organisme : NIGMS NIH HHS
ID : P30 GM124165
Pays : United States
Organisme : NCCIH NIH HHS
ID : P50 AT002776
Pays : United States
Organisme : NIH HHS
ID : S10 OD020062
Pays : United States
Organisme : NIGMS NIH HHS
ID : R15 GM143724
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier Ltd. All rights reserved.
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