Ezurpimtrostat
Ezurpimtrostat is an orally bioavailable, quinolone-derived, small molecule inhibitor of palmitoyl-protein thioesterase 1 (PPT1), with potential antineoplastic activity. Upon oral administration, ezurpimtrostat targets and inhibits the activity of PPT1 and induces lysosomal disruption, which results in the inhibition of autophagy and the induction of apoptosis via caspase activation. This may inhibit tumor cell proliferation and tumor growth. PPT1, a lysosomal thioesterase that plays an important role in lysosomal function and autophagy, is overexpressed in certain cancers. It has lysosomotropic properties which may explain lysosomal disruption independant of PPT1 inhibtion
General
Type : Piperidine, Quinoline
Chemical_Nomenclature : 4-[4-(tert-butylamino)piperidin-1-yl]-N-[(4-chlorophenyl)methyl]quinolin-2-amine
Canonical SMILES : CC(C)(C)NC1CCN(CC1)C2=CC(=NC3=CC=CC=C32)NCC4=CC=C(C=C4)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)
InChIKey : QVXSJSXAVQJXOV-UHFFFAOYSA-N
Other name(s) : MS6LGW5JFK || GNS561 || GNS-561 || UNII-MS6LGW5JFK || 2-((4-Chlorobenzyl)amino)-4-(4-tert-butylaminopiperidin-1-yl)quinoline || CHEMBL5095179
MW : 423
Formula : C25H31ClN4
CAS_number : 1914148-72-3
PubChem : 121305180
UniChem : QVXSJSXAVQJXOV-UHFFFAOYSA-N
Target
Families : Ezurpimtrostat ligand of proteins in family
Palmitoyl-protein_thioesterase
Protein :
human-PPT1
References (6)
| Title : GNS561, a clinical-stage PPT1 inhibitor, is efficient against hepatocellular carcinoma via modulation of lysosomal functions - Brun_2022_Autophagy_18_678 |
| Author(s) : Brun S , Bestion E , Raymond E , Bassissi F , Jilkova ZM , Mezouar S , Rachid M , Novello M , Tracz J , Hama A , Lalmanach G , Vanderlynden L , Legouffe R , Stauber J , Schubert T , Plach MG , Courcambeck J , Drouot C , Jacquemot G , Serdjebi C , Roth G , Baudoin JP , Ansaldi C , Decaens T , Halfon P |
| Ref : Autophagy , 18 :678 , 2022 |
| Abstract : |
| PubMedSearch : Brun_2022_Autophagy_18_678 |
| PubMedID: 34740311 |
| Gene_locus related to this paper: human-PPT1 |
| Title : GNS561 Exhibits Potent Antiviral Activity against SARS-CoV-2 through Autophagy Inhibition - Bestion_2022_Viruses_14_132 |
| Author(s) : Bestion E , Zandi K , Belouzard S , Andreani J , Lepidi H , Novello M , Rouquairol C , Baudoin JP , Rachid M , La Scola B , Mege JL , Dubuisson J , Schinazi RF , Mezouar S , Halfon P |
| Ref : Viruses , 14 :132 , 2022 |
| Abstract : |
| PubMedSearch : Bestion_2022_Viruses_14_132 |
| PubMedID: 35062337 |
| Title : First-In-Human Effects of PPT1 Inhibition Using the Oral Treatment with GNS561\/Ezurpimtrostat in Patients with Primary and Secondary Liver Cancers - Harding_2022_Liver.Cancer_11_268 |
| Author(s) : Harding JJ , Awada A , Roth G , Decaens T , Merle P , Kotecki N , Dreyer C , Ansaldi C , Rachid M , Mezouar S , Menut A , Bestion EN , Paradis V , Halfon P , Abou-Alfa GK , Raymond E |
| Ref : Liver Cancer , 11 :268 , 2022 |
| Abstract : |
| PubMedSearch : Harding_2022_Liver.Cancer_11_268 |
| PubMedID: 35949290 |
| Title : GNS561, a New Autophagy Inhibitor Active against Cancer Stem Cells in Hepatocellular Carcinoma and Hepatic Metastasis from Colorectal Cancer - Brun_2021_J.Cancer_12_5432 |
| Author(s) : Brun S , Pascussi JM , Gifu EP , Bestion E , Macek-Jilkova Z , Wang G , Bassissi F , Mezouar S , Courcambeck J , Merle P , Decaens T , Pannequin J , Halfon P , Caron de Fromentel C |
| Ref : J Cancer , 12 :5432 , 2021 |
| Abstract : |
| PubMedSearch : Brun_2021_J.Cancer_12_5432 |
| PubMedID: 34405006 |
| Title : GNS561 acts as a potent anti-fibrotic and pro-fibrolytic agent in liver fibrosis through TGF-beta1 inhibition - Bestion_2020_Ther.Adv.Chronic.Dis_11_2040622320942042 |
| Author(s) : Bestion E , Jilkova ZM , Mege JL , Novello M , Kurma K , Pour STA , Lalmanach G , Vanderlynden L , Fizanne L , Bassissi F , Rachid M , Tracz J , Boursier J , Courcambeck J , Serdjebi C , Ansaldi C , Decaens T , Halfon P , Brun S |
| Ref : Ther Adv Chronic Dis , 11 :2040622320942042 , 2020 |
| Abstract : |
| PubMedSearch : Bestion_2020_Ther.Adv.Chronic.Dis_11_2040622320942042 |
| PubMedID: 32728410 |
| Title : GNS561, a new lysosomotropic small molecule, for the treatment of intrahepatic cholangiocarcinoma - Brun_2019_Invest.New.Drugs_37_1135 |
| Author(s) : Brun S , Bassissi F , Serdjebi C , Novello M , Tracz J , Autelitano F , Guillemot M , Fabre P , Courcambeck J , Ansaldi C , Raymond E , Halfon P |
| Ref : Invest New Drugs , 37 :1135 , 2019 |
| Abstract : |
| PubMedSearch : Brun_2019_Invest.New.Drugs_37_1135 |
| PubMedID: 30778887 |