DC661
目录号 : GC19485
DC661是一种能够抑制棕榈酰蛋白硫酯酶1（PPT1）并有效抑制细胞自噬的小分子化合物，可作为抗溶酶体剂。
Cas No.:1872387-43-3
Sample solution is provided at 25 µL, 10mM.
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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[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.
DC661是一种能够抑制棕榈酰蛋白硫酯酶1（PPT1）并有效抑制细胞自噬的小分子化合物，可作为抗溶酶体剂[1-2]。DC661主要被用于治疗癌症的相关研究中[3-4]。
在体外，DC661（1.5-3μM）预处理人脐静脉内皮细胞（HUVECs）30分钟，随后在缺氧条件下处理5.5小时，DC661显著抑制PPT1的表达，同时降低血管生成反应[5]。DC661（0.5–3μM）预处理肝癌细胞Hep 3B和Hep 1-6细胞6–24小时，随后以索拉非尼（1.5–10μM）刺激24–48小时，DC661显著抑制PPT1表达和自噬活性，同时增强索拉非尼敏感性[6]。
在体内，DC661（3mg/kg/d）通过腹腔注射处理黑色素瘤肿瘤移植小鼠（Ppt1条件性敲除鼠），持续21天，DC661对黑色素瘤肿瘤发生和生长无影响[7]。DC661（10mM，5μl/天；连续6周）通过脑立体定位注射至铅暴露（200mg/kg/天；连续6周）的Wistar大鼠海马体。DC661显著抑制海马神经元自噬水平并上调IGF-1信号通路活性。DC661处理显著激活IGF-1/PI3K/Akt/mTOR通路活性，逆转铅诱导的自噬过度激活，改善海马神经元功能[8]。
| 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 | ||
| 分子式 | C₃₁H₃₉Cl₂N₅ | 分子量 | 552.58 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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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 |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet