GNS561, a clinical-stage PPT1 inhibitor, is efficient against hepatocellular carcinoma
Antineoplastic Agents
/ pharmacology
Autophagosomes
/ metabolism
Autophagy
/ physiology
Carcinoma, Hepatocellular
/ drug therapy
Humans
Liver Neoplasms
/ drug therapy
Lysosomes
/ metabolism
Membrane Proteins
/ metabolism
Sirolimus
/ pharmacology
TOR Serine-Threonine Kinases
/ metabolism
Thiolester Hydrolases
/ metabolism
Antitumor
PPT1
autophagy
liver cancer
lysosome
mtor
Journal
Autophagy
ISSN: 1554-8635
Titre abrégé: Autophagy
Pays: United States
ID NLM: 101265188
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
pubmed:
7
11
2021
medline:
21
4
2022
entrez:
6
11
2021
Statut:
ppublish
Résumé
Hepatocellular carcinoma is the most frequent primary liver cancer. Macroautophagy/autophagy inhibitors have been extensively studied in cancer but, to date, none has reached efficacy in clinical trials. In this study, we demonstrated that GNS561, a new autophagy inhibitor, whose anticancer activity was previously linked to lysosomal cell death, displayed high liver tropism and potent antitumor activity against a panel of human cancer cell lines and in two hepatocellular carcinoma in vivo models. We showed that due to its lysosomotropic properties, GNS561 could reach and specifically inhibited its enzyme target, PPT1 (palmitoyl-protein thioesterase 1), resulting in lysosomal unbound Zn
Identifiants
pubmed: 34740311
doi: 10.1080/15548627.2021.1988357
pmc: PMC9037544
doi:
Substances chimiques
Antineoplastic Agents
0
Membrane Proteins
0
TOR Serine-Threonine Kinases
EC 2.7.11.1
Thiolester Hydrolases
EC 3.1.2.-
PPT1 protein, human
EC 3.1.2.22
Sirolimus
W36ZG6FT64
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
678-694Références
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