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Chemical Structure| 1872387-43-3 Chemical Structure| 1872387-43-3

Structure of DC661
CAS No.: 1872387-43-3

Chemical Structure| 1872387-43-3

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DC661 is a potent palmitoyl-protein thioesterase 1 (PPT1) inhibitor, inhibits autophagy, and acts as an anti-lysosomal agent. Anti-cancer activity[1].

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Product Citations

Product Citations

Sneha Singh ; Faraz Ahmad ; Hariprasad Aruri ; Susmita Das ; Prahlad Parajuli ; Navnath S. Gavande , et al.

Abstract: Zika virus (ZIKV) is a re-emerging RNA virus that is known to cause ocular and neurological abnormalities in infants. ZIKV exploits autophagic processes in infected cells to enhance its replication and spread. Thus, autophagy inhibitors have emerged as a potent therapeutic target to combat RNA viruses, with (HCQ) being one of the most promising candidates. In this study, we synthesized several novel small-molecule quinoline derivatives, assessed their antiviral activity, and determined the underlying molecular mechanisms. Among the nine synthesized analogs, two lead candidates, labeled GL-287 and GL-382, significantly attenuated ZIKV replication in human ocular cells, primarily by inhibiting autophagy. These two compounds surpassed the antiviral efficacy of and other existing autophagy inhibitors, such as , , and GNS561. Moreover, unlike , these novel analogs did not exhibit cytotoxicity in the ocular cells. Treatment with compounds GL-287 and GL-382 in ZIKV-infected cells increased the abundance of LC3 puncta, indicating the disruption of the autophagic process. Furthermore, compounds GL-287 and GL-382 effectively inhibited the ZIKV-induced innate inflammatory response in ocular cells. Collectively, our study demonstrates the safe and potent antiviral activity of novel autophagy inhibitors against ZIKV.

Keywords: Autophagy ; Quinoline derivatives ; Zika virus ; Antivirals ; Eye ; Hydroxychloroquine

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Product Details of DC661

CAS No. :1872387-43-3
Formula : C31H39Cl2N5
M.W : 552.58
SMILES Code : CN(CCCCCCNC1=CC=NC2=CC(Cl)=CC=C12)CCCCCCNC3=CC=NC4=CC(Cl)=CC=C34
MDL No. :MFCD31812586
InChI Key :VJKCWFZTSDXOBS-UHFFFAOYSA-N
Pubchem ID :130467298

Safety of DC661

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
A375P cells 3 µM 24 h To evaluate the effect of DC661 on PPT1 enzymatic activity and cell viability. Results showed that DC661 significantly reduced PPT1 enzymatic activity and led to loss of cell viability. Autophagy. 2025 Feb;21(2):394-406
MIA PaCa-2 pancreatic cancer cells 3 μM 48 h Assess cell viability, DC661 significantly reduced cell viability J Clin Invest. 2023 Apr 17;133(8):e164596.
RKO colon carcinoma cells 3 μM 48 h Assess cell viability, DC661 significantly reduced cell viability J Clin Invest. 2023 Apr 17;133(8):e164596.
A375P melanoma cells 3 μM 48 h Assess cell viability, DC661 significantly reduced cell viability J Clin Invest. 2023 Apr 17;133(8):e164596.
Mouse bone marrow-derived macrophages (BMDMs) 0.6 μM 24 h Induced M2 to M1 phenotype switching, evidenced by increased iNOS expression and decreased ARG1 and RETNLA/FIZZ1 expression. JCI Insight. 2020 Sep 3;5(17):e133225
RAW 264.7 mouse macrophages 0.6 μM 24 h Induced M2 to M1 phenotype switching, evidenced by increased iNOS expression and decreased ARG1 and RETNLA/FIZZ1 expression. JCI Insight. 2020 Sep 3;5(17):e133225
Hep 1-6 3 µM 6 h DC661 induced lysosomal membrane permeability, caused lysosomal deacidification, inhibited autophagy and enhanced sorafenib sensitivity in HCC cells. Cancer Cell Int. 2022 Mar 11;22(1):115
Hep 3B 3 µM 6 h DC661 induced lysosomal membrane permeability, caused lysosomal deacidification, inhibited autophagy and enhanced sorafenib sensitivity in HCC cells. Cancer Cell Int. 2022 Mar 11;22(1):115
A375P cells 0-1000 nM 2 weeks To assess the inhibitory effect of DC661 on long-term clonogenic growth, results showed that DC661 suppressed clonogenic growth more effectively than Lys05 or HCQ. Cancer Discov. 2019 Feb;9(2):220-229
A375P cells 3 μM 6 h To evaluate the effect of DC661 on lysosomal deacidification, results showed that DC661 caused significantly greater lysosomal deacidification compared to Lys05 or HCQ. Cancer Discov. 2019 Feb;9(2):220-229
A375P cells 0-100 μM 1 h To assess the inhibitory effect of DC661 on autophagic flux by microscopy, results showed that DC661 inhibited autophagic flux more effectively than Lys05 or HCQ. Cancer Discov. 2019 Feb;9(2):220-229
A375P cells 0.1-10 μM 6 h To evaluate the effect of DC661 on the accumulation of autophagic vesicle marker LC3BII, results showed that DC661 more significantly inhibited autophagic flux at lower concentrations compared to Lys05 or HCQ. Cancer Discov. 2019 Feb;9(2):220-229
A375P 3 μM 24 h Investigate the effect of DC661 on the proteome and lipidome of A375P cells, finding that DC661 significantly upregulates lipid metabolism enzymes and lipid species Cancer Discov. 2023 Feb 6;13(2):454-473

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
C57BL/6J mice Hepa1-6 subcutaneous HCC model Intraperitoneal injection 3 mg/kg Daily DC661 enhanced the efficacy of anti-PD-1 antibody in HCC, significantly inhibited the growth of subcutaneous tumors, and increased tumor infiltration of MHC-II+ M1 macrophages and CD8+ T cells. J Immunother Cancer. 2023 Jun;11(6):e006655
C57BL/6 mice Hep 1-6-SR cell derived HCC tumor model Intraperitoneal injection 3 mg/kg Once daily for 21 days DC661 combined with sorafenib significantly inhibited tumor growth and prolonged survival time in mice. Cancer Cell Int. 2022 Mar 11;22(1):115
NSG mice HT29 colorectal cancer xenograft model Intraperitoneal injection 3 mg/kg Daily To evaluate the inhibitory effect of DC661 on tumor growth, results showed that DC661 significantly suppressed tumor growth without affecting mouse weight. Cancer Discov. 2019 Feb;9(2):220-229
C57BL6 mice B16-F10 melanoma model Intraperitoneal injection 0.5 mg/kg Once every two days Investigate the effect of DC661 combined with eliglustat on B16-F10 tumor growth, finding that the combination significantly inhibited tumor growth Cancer Discov. 2023 Feb 6;13(2):454-473

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.81mL

0.36mL

0.18mL

9.05mL

1.81mL

0.90mL

18.10mL

3.62mL

1.81mL

 

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