DC661

Inhibitor of palmitoyl-protein thioesterase 1. The lysosomal enzyme palmitoyl-protein thioesterase 1 (PPT1) removes thioester-linked fatty acid groups from membrane-bound proteins to facilitate their proteolysis. A lack of PPT1 (due to gene mutations) causes the progressive death of cortical neurons and is responsible for infantile neural ceroid lipofuscinosis (INCL), a severe neurodegenerative disorder in children. Conversely, PPT1 is often over-expressed in cancer, and considered as a valid target to control tumor growth.

General

Type : Quinoline

Chemical_Nomenclature : N-(7-chloroquinolin-4-yl)-N'-[6-[(7-chloroquinolin-4-yl)amino]hexyl]-N'-methylhexane-1,6-diamine

Canonical SMILES : CN(CCCCCCNC1=C2C=CC(=CC2=NC=C1)Cl)CCCCCCNC3=C4C=CC(=CC4=NC=C3)Cl

InChI : InChI=1S\/C31H39Cl2N5\/c1-38(20-8-4-2-6-16-34-28-14-18-36-30-22-24(32)10-12-26(28)30)21-9-5-3-7-17-35-29-15-19-37-31-23-25(33)11-13-27(29)31\/h10-15,18-19,22-23H,2-9,16-17,20-21H2,1H3,(H,34,36)(H,35,37)

InChIKey : VJKCWFZTSDXOBS-UHFFFAOYSA-N

Other name(s) : N1-(7-chloroquinolin-4-yl)-N6-(6-((7-chloroquinolin-4-yl)amino)hexyl)-N6-methylhexane-1,6-diamine  ||  7-chloro-N-[6-({6-[(7-chloroquinolin-4-yl)amino]hexyl}(methyl)amino)hexyl]quinolin-4-amine  ||  CHEMBL4873725  ||  SCHEMBL19399303


MW : 552.6

Formula : C31H39Cl2N5

CAS_number : 1872387-43-3

PubChem : 130467298

UniChem : VJKCWFZTSDXOBS-UHFFFAOYSA-N

Target

Families : DC661 ligand of proteins in family
Palmitoyl-protein_thioesterase

Protein :
human-PPT1

References (15)

Title : Novel quinoline substituted autophagy inhibitors attenuate Zika virus replication in ocular cells - Singh_2024_Virus.Res_347_199419
Author(s) : Singh S , Ahmad F , Aruri H , Das S , Parajuli P , Gavande NS , Singh PK , Kumar A
Ref : Virus Res , 347 :199419 , 2024
Abstract :
PubMedSearch : Singh_2024_Virus.Res_347_199419
PubMedID: 38880335
Gene_locus related to this paper: human-PPT1

Title : Enhancing Gpx1 palmitoylation to inhibit angiogenesis by targeting PPT1 - Ma_2024_Redox.Biol_77_103376
Author(s) : Ma Y , Yuan X , Wei A , Li X , Patar A , Su S , Wang S , Ma G , Zhu J , Kong E
Ref : Redox Biol , 77 :103376 , 2024
Abstract :
PubMedSearch : Ma_2024_Redox.Biol_77_103376
PubMedID: 39423458
Gene_locus related to this paper: human-PPT1

Title : Divergent effects of acute and chronic PPT1 inhibition in melanoma - Crissey_2024_Autophagy__1
Author(s) : Crissey MAS , Versace A , Bhardwaj M , Jain V , Liu S , Singh A , Beer LA , Tang HY , Villanueva J , Gimotty PA , Xu X , Amaravadi RK
Ref : Autophagy , :1 , 2024
Abstract :
PubMedSearch : Crissey_2024_Autophagy__1
PubMedID: 39265628
Gene_locus related to this paper: human-PPT1

Title : DIRAS3 induces autophagy and enhances sensitivity to anti-autophagic therapy in KRAS-driven pancreatic and ovarian carcinomas - Bildik_2024_Autophagy_20_675
Author(s) : Bildik G , Gray JP , Mao W , Yang H , Ozyurt R , Orellana VR , De Wever O , Carey MS , Bast RC , Lu Z
Ref : Autophagy , 20 :675 , 2024
Abstract :
PubMedSearch : Bildik_2024_Autophagy_20_675
PubMedID: 38169324
Gene_locus related to this paper: human-PPT1

Title : Mechanism of autophagy mediated by IGF-1 signaling pathway in the neurotoxicity of lead in pubertal rats - Zhang_2023_Ecotoxicol.Environ.Saf_251_114557
Author(s) : Zhang B , Li H , Wang Y , Li Y , Zhou Z , Hou X , Zhang X , Liu T
Ref : Ecotoxicology & Environmental Safety , 251 :114557 , 2023
Abstract :
PubMedSearch : Zhang_2023_Ecotoxicol.Environ.Saf_251_114557
PubMedID: 36652739
Gene_locus related to this paper: human-PPT1

Title : Intratumoral PPT1-positive macrophages determine immunosuppressive contexture and immunotherapy response in hepatocellular carcinoma - Weng_2023_J.Immunother.Cancer_11_
Author(s) : Weng J , Liu S , Zhou Q , Xu W , Xu M , Gao D , Shen Y , Yi Y , Shi Y , Dong Q , Zhou C , Ren N
Ref : J Immunother Cancer , 11 : , 2023
Abstract :
PubMedSearch : Weng_2023_J.Immunother.Cancer_11_
PubMedID: 37385725
Gene_locus related to this paper: human-PPT1

Title : Lysosomal lipid peroxidation mediates immunogenic cell death - Phadatare_2023_J.Clin.Invest_133_
Author(s) : Phadatare P , Debnath J
Ref : J Clinical Investigation , 133 : , 2023
Abstract :
PubMedSearch : Phadatare_2023_J.Clin.Invest_133_
PubMedID: 37066873
Gene_locus related to this paper: human-PPT1

Title : Advances of Protein Palmitoylation in Tumor Cell Deaths - Lin_2023_Cancers.(Basel)_15_
Author(s) : Lin X , Shi Y , Zhan Y , Xing Y , Li Y , Zhou Z , Chen G
Ref : Cancers (Basel) , 15 : , 2023
Abstract :
PubMedSearch : Lin_2023_Cancers.(Basel)_15_
PubMedID: 38067206
Gene_locus related to this paper: human-PPT1

Title : Targeting UGCG Overcomes Resistance to Lysosomal Autophagy Inhibition - Jain_2023_Cancer.Discov_13_454
Author(s) : Jain V , Harper SL , Versace AM , Fingerman D , Brown GS , Bhardwaj M , Crissey MAS , Goldman AR , Ruthel G , Liu Q , Zivkovic A , Stark H , Herlyn M , Gimotty PA , Speicher DW , Amaravadi RK
Ref : Cancer Discov , 13 :454 , 2023
Abstract :
PubMedSearch : Jain_2023_Cancer.Discov_13_454
PubMedID: 36331284
Gene_locus related to this paper: human-PPT1

Title : Lysosomal lipid peroxidation regulates tumor immunity - Bhardwaj_2023_J.Clin.Invest_133_
Author(s) : Bhardwaj M , Lee JJ , Versace AM , Harper SL , Goldman AR , Crissey MAS , Jain V , Singh MP , Vernon M , Aplin AE , Lee S , Morita M , Winkler JD , Liu Q , Speicher DW , Amaravadi RK
Ref : J Clinical Investigation , 133 : , 2023
Abstract :
PubMedSearch : Bhardwaj_2023_J.Clin.Invest_133_
PubMedID: 36795483
Gene_locus related to this paper: human-PPT1

Title : Poly (ADP-ribose) polymerase 1-mediated defective mitophagy contributes to painful diabetic neuropathy in the db\/db model - Yuan_2022_J.Neurochem_162_276
Author(s) : Yuan P , Song F , Zhu P , Fan K , Liao Q , Huang L , Liu Z
Ref : Journal of Neurochemistry , 162 :276 , 2022
Abstract :
PubMedSearch : Yuan_2022_J.Neurochem_162_276
PubMedID: 35263449
Gene_locus related to this paper: human-PPT1

Title : High PPT1 expression predicts poor clinical outcome and PPT1 inhibitor DC661 enhances sorafenib sensitivity in hepatocellular carcinoma - Xu_2022_Cancer.Cell.Int_22_115
Author(s) : Xu J , Su Z , Cheng X , Hu S , Wang W , Zou T , Zhou X , Song Z , Xia Y , Gao Y , Zheng Q
Ref : Cancer Cell Int , 22 :115 , 2022
Abstract :
PubMedSearch : Xu_2022_Cancer.Cell.Int_22_115
PubMedID: 35277179
Gene_locus related to this paper: human-PPT1

Title : Binding of hydroxychloroquine and chloroquine dimers to palmitoyl-protein thioesterase 1 (PPT1) and its glycosylated forms: a computational approach - Vergoten_2022_J.Biomol.Struct.Dyn_40_8197
Author(s) : Vergoten G , Bailly C
Ref : J Biomol Struct Dyn , 40 :8197 , 2022
Abstract :
PubMedSearch : Vergoten_2022_J.Biomol.Struct.Dyn_40_8197
PubMedID: 33876698

Title : PPT1 inhibition enhances the antitumor activity of anti-PD-1 antibody in melanoma - Sharma_2020_JCI.Insight_5_
Author(s) : Sharma G , Ojha R , Noguera-Ortega E , Rebecca VW , Attanasio J , Liu S , Piao S , Lee JJ , Nicastri MC , Harper SL , Ronghe A , Jain V , Winkler JD , Speicher DW , Mastio J , Gimotty PA , Xu X , Wherry EJ , Gabrilovich DI , Amaravadi RK
Ref : JCI Insight , 5 : , 2020
Abstract :
PubMedSearch : Sharma_2020_JCI.Insight_5_
PubMedID: 32780726
Gene_locus related to this paper: human-PPT1

Title : PPT1 Promotes Tumor Growth and Is the Molecular Target of Chloroquine Derivatives in Cancer - Rebecca_2019_Cancer.Discov_9_220
Author(s) : Rebecca VW , Nicastri MC , Fennelly C , Chude CI , Barber-Rotenberg JS , Ronghe A , McAfee Q , McLaughlin NP , Zhang G , Goldman AR , Ojha R , Piao S , Noguera-Ortega E , Martorella A , Alicea GM , Lee JJ , Schuchter LM , Xu X , Herlyn M , Marmorstein R , Gimotty PA , Speicher DW , Winkler JD , Amaravadi RK
Ref : Cancer Discov , 9 :220 , 2019
Abstract :
PubMedSearch : Rebecca_2019_Cancer.Discov_9_220
PubMedID: 30442709
Gene_locus related to this paper: human-PPT1