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
Click here for help

2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

✖
Click here for structure editor
Physico-chemical Properties
Click here for help

Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

✖
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
SMILES / InChI / InChIKey
Click here for help

SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

✖
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)
InChI Key QVXSJSXAVQJXOV-UHFFFAOYSA-N
References
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]