ezurpimtrostat   Click here for help

GtoPdb Ligand ID: 11991

Synonyms: GNS-561 | GNS561
Compound class: Synthetic organic
Comment: Ezurpimtrostat (GNS561) is a small molecule inhibitor of palmitoyl-protein thioesterase 1 (PPT1). It induces lysosomal dysregulation which leads to inhibition of late-stage autophagy and cell death. Antitumour and antiviral activities have been demonstrated in vitro and in vivo [1-5].
2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 4
Hydrogen bond donors 2
Rotatable bonds 6
Topological polar surface area 40.19
Molecular weight 422.22
XLogP 6.62
No. Lipinski's rules broken 1
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Canonical SMILES Clc1ccc(cc1)CNc1cc(N2CCC(CC2)NC(C)(C)C)c2c(n1)cccc2
Isomeric SMILES CC(C)(C)NC1CCN(CC1)c1cc(nc2ccccc12)NCc1ccc(cc1)Cl
InChI InChI=1S/C25H31ClN4/c1-25(2,3)29-20-12-14-30(15-13-20)23-16-24(28-22-7-5-4-6-21(22)23)27-17-18-8-10-19(26)11-9-18/h4-11,16,20,29H,12-15,17H2,1-3H3,(H,27,28)
1. Bestion E, Zandi K, Belouzard S, Andreani J, Lepidi H, Novello M, Rouquairol C, Baudoin JP, Rachid M, La Scola B et al.. (2022)
GNS561 Exhibits Potent Antiviral Activity against SARS-CoV-2 through Autophagy Inhibition.
Viruses, 14 (1). DOI: 10.3390/v14010132 [PMID:35062337]
2. Brun S, Bassissi F, Serdjebi C, Novello M, Tracz J, Autelitano F, Guillemot M, Fabre P, Courcambeck J, Ansaldi C et al.. (2019)
GNS561, a new lysosomotropic small molecule, for the treatment of intrahepatic cholangiocarcinoma.
Invest New Drugs, 37 (6): 1135-1145. [PMID:30778887]
3. Brun S, Bestion E, Raymond E, Bassissi F, Jilkova ZM, Mezouar S, Rachid M, Novello M, Tracz J, Hamaï A et al.. (2022)
GNS561, a clinical-stage PPT1 inhibitor, is efficient against hepatocellular carcinoma via modulation of lysosomal functions.
Autophagy, 18 (3): 678-694. [PMID:34740311]
4. Brun S, Pascussi JM, Gifu EP, Bestion E, Macek-Jilkova Z, Wang G, Bassissi F, Mezouar S, Courcambeck J, Merle P et al.. (2021)
GNS561, a New Autophagy Inhibitor Active against Cancer Stem Cells in Hepatocellular Carcinoma and Hepatic Metastasis from Colorectal Cancer.
J Cancer, 12 (18): 5432-5438. [PMID:34405006]
5. Halfon P, Bestion E, Zandi K, Andreani J, Baudoin JP, La Scola B, Mege JL, Mezouar S, Schinazi RF. (2020)
GNS561 exhibits potent in vitro antiviral activity against SARS-CoV-2 through autophagy inhibition.
bioRxiv,. [PMID:33052342]