Recent Progress in the Discovery of Allosteric Inhibitors of Kidney-Type Glutaminase.
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:
10 01 2019
10 01 2019
Historique:
pubmed:
4
7
2018
medline:
15
10
2019
entrez:
4
7
2018
Statut:
ppublish
Résumé
Kidney-type glutaminase (GLS), the first enzyme in the glutaminolysis pathway, catalyzes the hydrolysis of glutamine to glutamate. GLS was found to be upregulated in many glutamine-dependent cancer cells. Therefore, selective inhibition of GLS has gained substantial interest as a therapeutic approach targeting cancer metabolism. Bis-2-[5-(phenylacetamido)-1,3,4-thiadiazol-2-yl]ethyl sulfide (BPTES), despite its poor physicochemical properties, has served as a key molecular template in subsequent efforts to identify more potent and drug-like allosteric GLS inhibitors. This review article provides an overview of the progress made to date in the development of GLS inhibitors and highlights the remarkable transformation of the unfavorable lead into "druglike" compounds guided by systematic SAR studies.
Identifiants
pubmed: 29969024
doi: 10.1021/acs.jmedchem.8b00327
pmc: PMC6335185
mid: NIHMS1003502
doi:
Substances chimiques
Enzyme Inhibitors
0
Sulfides
0
Thiadiazoles
0
bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide
0
Glutaminase
EC 3.5.1.2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
46-59Subventions
Organisme : NCI NIH HHS
ID : R01 CA193895
Pays : United States
Organisme : NINDS NIH HHS
ID : R21 NS074151
Pays : United States
Organisme : NIMH NIH HHS
ID : P30 MH075673
Pays : United States
Organisme : NIMH NIH HHS
ID : R25 MH080661
Pays : United States
Organisme : NCI NIH HHS
ID : F32 CA200278
Pays : United States
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