CB-5339 |
Catalog No.GC20117
One-Click Copy Product Info
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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.
Products are for research use only. Not for human use. We do not sell to patients.
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.
| Cell experiment [1]: | |
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Cell lines |
HCT-116 cells |
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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. |
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Reaction Conditions |
0, 0.1, 0.5, 1, 2, 4, 6, 8, and 10μM; 72h |
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Applications |
CB-5339 treatment significantly inhibited the viability of HCT-116 cells in a dose-dependent manner. |
| Animal experiment [2]: | |
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Animal models |
Male NSG mice |
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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. |
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Dosage form |
90mg/kg/day for 4 days; p.o. |
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Applications |
CB-5339 treatment decreased circulating leukemic cells and prolonged mice survival. |
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References: |
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| Cas No. | 1863952-15-1 | SDF | |
| Chemical Name | 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 | ||
| Formula | C24H24N6O | M.Wt | 412.49 |
| Solubility | DMSO : 41.67 mg/mL | 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 | 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 |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
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 15 reference(s) in Google Scholar.)