CB-5339
目录号 : GC20117CB-5339是一种高效、选择性且具有口服活性的含缬酪肽蛋白/p97抑制剂，IC50值为9nM。
Cas No.:1863952-15-1
Sample solution is provided at 25 µL, 10mM.
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CB-5339 is a potent and selective, orally bioavailable small molecule inhibitor of valosin containing protein (VCP)/p97, with an IC50 value of 9nM[1]. CB-5339 targets the D2 ATPase domain of p97, effectively inhibiting p97 function, triggering the accumulation of ubiquitinated proteins, and inducing proteotoxic stress[2]. CB-5339 has been widely used as an anti-cancer agent to inhibit the proliferation of solid tumors and hematological tumors[3].
In vitro, CB-5339 treatment for 72 hours significantly inhibited the proliferation of HCT-116 cells, with an IC50 value of 0.7±0.07μM[4]. After 48 hours of treatment with CB-5339, the viability of 17-71 cells and DH82 cells was significantly inhibited, with IC50 values of 188nM and 486nM, respectively[5]. Treatment with 2μM CB-5339 for 7 days significantly induced senescence in RBE cells[6].
In vivo, CB-5339 treatment (90mg/kg; p.o.) for 4 days reduced the number of circulating leukemia cells in the MLL-AF9 syngeneic mouse model and prolonged the survival time of the mice[7]. CB-5339 (50mg/kg/day; p.o.) combined with venetoclax (30mg/kg/day; p.o.) for 3 weeks significantly reduced the acute myelocytic leukemia (AML) burden in NSG mice, and increased the median survival time and overall survival time, without causing obvious toxicity[8].
References:
[1] Kilgas S, Ramadan K. Inhibitors of the ATPase p97/VCP: From basic research to clinical applications[J]. Cell Chemical Biology, 2023, 30(1): 3-21.
[2] Carrera Espinoza M J, Tucker S K, Sureshkumar S, et al. Harnessing p97/VCP: A Transformative AAA+ ATPase Target for Next-Generation Cancer Therapeutics[J]. Cancers, 2025, 17(18): 2945.
[3] Benajiba L, Carraway H E, Hamad N, et al. Trials in progress: a phase I study to evaluate the safety and pharmacokinetic profiles of CB-5339 in participants with relapsed/refractory acute myeloid leukemia or relapsed/refractory intermediate or high-risk myelodysplastic syndrome[J]. Blood, 2020, 136: 21.
[4] Wang X, Wen T, Miao H, et al. Discovery of a new class of valosine containing protein (VCP/P97) inhibitors for the treatment of colorectal cancer[J]. Bioorganic & Medicinal Chemistry, 2022, 74: 117050.
[5] LeBlanc A K, Mazcko C N, Fan T M, et al. Comparative oncology assessment of a novel inhibitor of valosin-containing protein in tumor-bearing dogs[J]. Molecular cancer therapeutics, 2022, 21(10): 1510-1523.
[6] Yang W, Wang S, Ji S, et al. CRISPR screens identify the ATPase VCP as a druggable therapeutic vulnerability in cholangiocarcinoma[J]. Proceedings of the National Academy of Sciences, 2025, 122(39): e2519568122.
[7] Roux B, Vaganay C, Vargas J D, et al. Targeting acute myeloid leukemia dependency on VCP-mediated DNA repair through a selective second-generation small-molecule inhibitor[J]. Science translational medicine, 2021, 13(587): eabg1168.
[8] Fiskus W C, Das K, Mill C P, et al. Efficacy of Vcp/p97 inhibitor, CB-5339, alone and in combinations against high-risk AML, including those with genetic lesion in TP53[J]. 2022.
CB-5339是一种高效、选择性且具有口服活性的含缬酪肽蛋白/p97抑制剂，IC50值为9nM[1]。CB-5339通过靶向p97蛋白的D2 ATP酶结构域，有效抑制p97功能，引发泛素化蛋白积累并诱导蛋白毒性应激[2]。CB-5339已作为抗癌剂广泛应用于实体瘤和血液系统肿瘤的增殖抑制研究[3]。
在体外，CB-5339处理72小时可显著抑制HCT-116细胞增殖，IC50值为0.7±0.07μM[4]。使用CB-5339处理48小时后，17-71细胞和DH82细胞的活力被显著抑制，IC50值分别为188nM和486nM[5]。用2μM的CB-5339处理RBE细胞7天，能显著诱导细胞衰老[6]。
在体内，口服CB-5339（90mg/kg/day；p.o.）治疗4天可减少MLL-AF9同源小鼠模型中的循环白血病细胞数量，并延长小鼠生存时间[7]。CB-5339（50mg/kg/day；p.o.）与venetoclax（30mg/kg/day; p.o.）联合给药3周，能显著减轻NSG小鼠的急性髓系白血病（AML）负荷，延长小鼠中位生存期和总生存期，且未引起明显毒性[8]。
| Cell experiment [1]: | |
Cell lines | HCT-116 cells |
Preparation Method | HCT-116 cells (2000 cells per well) were seeded in 96-well cell culture plates at a volume of 90μl per well, and cultured at 37°C with 5% CO2 for 24 hours. CB-5339 was dissolved in DMSO (concentration less than 0.1%) and diluted to different concentrations (0, 0.1, 0.5, 1, 2, 4, 6, 8, and 10μM). Then, different concentrations of CB-5339 were incubated with the cells together under 37°C and 5% CO2 conditions. After 72 hours of treatment, the absorbance at 450 nm was measured to determine the cell viability. |
Reaction Conditions | 0, 0.1, 0.5, 1, 2, 4, 6, 8, and 10μM; 72h |
Applications | CB-5339 treatment significantly inhibited the viability of HCT-116 cells in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | Male NSG mice |
Preparation Method | Male NSG mice were raised under standard conditions. 2×105 MLL-AF9 cells were injected into the tail veins of 8-week-old male NSG mice. After confirming the successful establishment of the xenograft model, the mice were randomly divided into two groups and treated with CB-5339 (90mg/kg/day; p.o.) or normal saline (0.5% methylcellulose) for 4 days. Then, peripheral blood samples of the mice were collected for analysis. |
Dosage form | 90mg/kg/day for 4 days; p.o. |
Applications | CB-5339 treatment decreased circulating leukemic cells and prolonged mice survival. |
References: | |
| Cas No. | 1863952-15-1 | SDF | |
| 化学名 | 1-(4-(benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide | ||
| Canonical SMILES | O=C(N)C1=CC=CC2=C1C=C(C)N2C3=NC(NCC4=CC=CC=C4)=C(CCCN5)C5=N3 | ||
| 分子式 | C24H24N6O | 分子量 | 412.49 |
| 溶解度 | DMSO : 41.67 mg/mL | 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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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.4243 mL | 12.1215 mL | 24.243 mL |
| 5 mM | 484.9 μL | 2.4243 mL | 4.8486 mL |
| 10 mM | 242.4 μL | 1.2122 mL | 2.4243 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.
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Quality Control & SDS
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- Purity: >98.00%
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