DC661 |
Catalog No.GC19485
One-Click Copy Product Info
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DC661 is a small-molecule compound capable of inhibiting palmitoyl-protein thioesterase 1 (PPT1) and effectively suppressing cellular autophagy, serving as an antilysosomal agent.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1872387-43-3
Sample solution is provided at 25 µL, 10mM.
DC661 is a small-molecule compound capable of inhibiting palmitoyl-protein thioesterase 1 (PPT1) and effectively suppressing cellular autophagy, serving as an antilysosomal agent[1-2]. DC661 is primarily utilized in cancer-related research[3-4].
In vitro, pretreatment of human umbilical vein endothelial cells (HUVECs) with DC661 (1.5–3μM) for 30 minutes, followed by 5.5 hours of hypoxia exposure, significantly inhibited PPT1 expression and reduced angiogenic responses[5]. Pretreatment of hepatocellular carcinoma cells Hep 3B and Hep 1-6 with DC661 (0.5–3μM) for 6–24 hours, followed by stimulation with sorafenib (1.5–10μM) for 24–48 hours, significantly suppressed PPT1 expression and autophagic activity while enhancing sensitivity to sorafenib[6].
In vivo, intraperitoneal injection of DC661 (3mg/kg/day) for 21 days in melanoma tumor-bearing mice (Ppt1 conditional knockout mice) showed no effect on melanoma tumor initiation or growth[7]. In a lead-exposed (200mg/kg/day for 6 weeks) Wistar rat model, hippocampal stereotactic administration of DC661 (10mM, 5μl/day for 6 weeks) significantly inhibited autophagy levels in hippocampal neurons and upregulated IGF-1 signaling pathway activity. DC661 treatment markedly activated the IGF-1/PI3K/Akt/mTOR pathway, reversed lead-induced excessive autophagy, and improved hippocampal neuronal function[8].
References:
[1] Weng J, Liu S, Zhou Q, et al. Intratumoral PPT1-positive macrophages determine immunosuppressive contexture and immunotherapy response in hepatocellular carcinoma. J Immunother Cancer. 2023 Jun;11(6):e006655.
[2] Jain V, Harper SL, Versace AM, et al. Amaravadi RK. Targeting UGCG Overcomes Resistance to Lysosomal Autophagy Inhibition. Cancer Discov. 2023 Feb 6;13(2):454-473.
[3] Bildik G, Gray JP, Mao W, et al. DIRAS3 induces autophagy and enhances sensitivity to anti-autophagic therapy in KRAS-driven pancreatic and ovarian carcinomas. Autophagy. 2024 Mar;20(3):675-691.
[4] Ferret L, Pol JG, Sauvat A, et al. Lysosomal membrane permeabilization enhances the anticancer effects of POLR1 (RNA polymerase I) transcription inhibitors. Autophagy. 2025 Oct;21(10):2246-2265.
[5] Ma Y, Yuan X, Wei A, et al. Enhancing Gpx1 palmitoylation to inhibit angiogenesis by targeting PPT1. Redox Biol. 2024 Nov;77:103376.
[6] Xu J, Su Z, Cheng X, et al. High PPT1 expression predicts poor clinical outcome and PPT1 inhibitor DC661 enhances sorafenib sensitivity in hepatocellular carcinoma. Cancer Cell Int. 2022 Mar 11;22(1):115.
[7] Crissey MAS, Versace A, Bhardwaj M, et al. Divergent effects of acute and chronic PPT1 inhibition in melanoma. Autophagy. 2025 Feb;21(2):394-406.
[8] Zhang B, Li H, Wang Y, et al. Mechanism of autophagy mediated by IGF-1 signaling pathway in the neurotoxicity of lead in pubertal rats. Ecotoxicol Environ Saf. 2023 Feb;251:114557.
| Cell experiment [1]: | |
Cell lines | HUVECs (human umbilical vein endothelial cells), HRECs (human retinal endothelial cells), and HEK293T cells |
Preparation Method | Cells were maintained in DMEM (HUVECs, HEK293T) or ECM medium (HRECs) supplemented with 10% fetal bovine serum (FBS) and antibiotics at 37°C, 5% CO₂. Cells were treated with DC661 at concentrations of 1.5–3μM for 6–24 hours. |
Reaction Conditions | 1.5–3μM; 6-24h |
Applications | DC661 significantly enhanced Gpx1 palmitoylation levels by inhibiting PPT1, leading to suppressed angiogenesis and cell migration in HUVECs and HRECs. DC661 reduced VEGF and HIF-1α expression under hypoxic conditions and decreased reactive oxygen species (ROS) by stabilizing Gpx1 activity. DC661 also inhibited cell proliferation and induced lysosomal deacidification, impairing autophagic flux. |
| Animal experiment [2]: | |
Animal models | Wistar rats (pubertal) |
Preparation Method | Rats were exposed to lead Acetate (200mg/kg/day) for 6 weeks. DC661 (10mM) was administered via stereotactic hippocampal injection (5μL/day) until the end of lead exposure. Hippocampal tissues and serum were collected for analysis. |
Dosage form | 10mM; 5μl/day; Hippocampal microinjection for 6 weeks. |
Applications | DC661 significantly inhibited lead-induced autophagy in hippocampal neurons, reduced LC3B and Beclin1 protein levels, and upregulated IGF-1, IGF-1R, p-Akt, and p-mTOR expression. DC661 attenuated lead-impaired learning and memory by modulating the IGF-1/PI3K/Akt/mTOR pathway, demonstrating neuroprotective effects against lead neurotoxicity. |
References: | |
| Cas No. | 1872387-43-3 | SDF | |
| Canonical SMILES | CN(CCCCCCNC1=CC=NC2=CC(Cl)=CC=C12)CCCCCCNC3=CC=NC4=CC(Cl)=CC=C34 | ||
| Formula | C₃₁H₃₉Cl₂N₅ | M.Wt | 552.58 |
| Solubility | Soluble in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.8097 mL | 9.0485 mL | 18.0969 mL |
| 5 mM | 361.9 μL | 1.8097 mL | 3.6194 mL |
| 10 mM | 181 μL | 904.8 μL | 1.8097 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
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Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 26 reference(s) in Google Scholar.)