CB-5083
Based on 48 publication(s) in Google Scholar
CB-5083 is a first-in-class, potent, selective, and orally bioavailable inhibitor of the p97 AAA ATPase/VCP. CB-5083 selectively inhibits p97 through its D2 site with the IC50 of 11 nM.
For research use only. We do not sell to patients.
- Purity: 99.90%
- CAS No.: 1542705-92-9
- Formula: C24H23N5O2
- Molecular Weight:413.47
-
Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
Publications Citing Use of MedChemExpress (MCE) CB-5083
More- Signal Transduct Target Ther. 2025 Jan 24;10(1):26. [Abstract]
- Nature. 2025 Feb;638(8050):519-527. [Abstract]
- Cell. 2020 Dec 10;183(6):1714-1731.e10. [Abstract]
- Mol Cell. 2025 Mar 20:S1097-2765(25)00152-2. [Abstract]
- Mol Cell. 2024 Dec 5:S1097-2765(24)00949-3. [Abstract]
- ACS Nano. 2025 Feb 11;19(5):5659-5679. [Abstract]
- Nat Commun. 2026 Feb 12;17(1):1214. [Abstract]
- Nat Commun. 2025 Dec 12;16(1):11092. [Abstract]
- Nat Commun. 2025 Nov 18;16(1):10094. [Abstract]
- Nat Commun. 2025 Oct 29;16(1):9554. [Abstract]
- Nat Commun. 2025 Feb 14;16(1):1634. [Abstract]
- Nat Commun. 2024 Aug 17;15(1):7089. [Abstract]
- Neuron. 2025 Aug 29:S0896-6273(25)00587-2. [Abstract]
- Adv Sci (Weinh). 2024 Jun;11(21):e2309010. [Abstract]
- Nat Chem Biol. 2023 Dec;19(12):1513-1523. [Abstract]
- Leukemia. 2019 Jul;33(7):1675-1686. [Abstract]
- Exp Mol Med. 2025 Jun;57(6):1308-1323. [Abstract]
- Sci Adv. 2021 May 14;7(20):eabg2099. [Abstract]
- J Immunother Cancer. 2025 Nov 19;13(11):e012652. [Abstract]
- Cell Death Dis. 2024 Nov 3;15(11):788. [Abstract]
- Proc Natl Acad Sci U S A. 2025 Sep 30;122(39):e2519568122. [Abstract]
- Biomed Pharmacother. 2024 Jun:175:116660. [Abstract]
- Cell Rep. 2021 May 25;35(8):109153. [Abstract]
- Genet Med. 2026 Apr 13.
- Pharmaceutics. 2025 Nov 20;17(11):1503. [Abstract]
- Mol Ther Oncolytics. 2020 Jun 23;18:215-225. [Abstract]
- Inflammation. 2024 Oct;47(5):1868-1883. [Abstract]
- PLoS Pathog. 2024 Oct 29;20(10):e1012674. [Abstract]
- Int J Mol Sci. 2024 Aug 20;25(16):9022. [Abstract]
- Mol Oncol. 2025 Jul 9. [Abstract]
- FASEB J. 2025 May 15;39(9):e70585. [Abstract]
- J Biol Chem. 2019 Dec 27;294(52):20084-20096. [Abstract]
- J Virol. 2021 Jun 24;95(14):e0053121. [Abstract]
- J Virol. 2021 Mar 25;95(8):e02399-20. [Abstract]
- Biochim Biophys Acta Gene Regul Mech. 2023 Jun;1866(2):194937. [Abstract]
- Mol Biol Cell. 2025 Jan 9:mbcE24100455. [Abstract]
- PLoS One. 2021 Aug 24;16(8):e0256640. [Abstract]
- Biochem Biophys Res Commun. 2021 Apr 16:549:150-156. [Abstract]
- bioRxiv. 2026 Feb 18:2026.02.17.706203. [Abstract]
- bioRxiv. 2026 Feb 5.
- bioRxiv. 2026 Jan 19.
- bioRxiv. 2025 Nov 19.
- Aalto University. 2025 Apr.
- Patent. US20240269139A1.
- bioRxiv. 2024 July 27.
- bioRxiv. 2024 July 08.
- Res Sq. 2024 Mar 29:rs.3.rs-4049366. [Abstract]
- bioRxiv. 2023: 2023 Feb 6.527237.
-
WB
-
In Vivo Efficacy Study
-
Flow Cytometry
-
WB
-
WB
Biological Activity
IC50: 11 nM (p97)[1]
|
Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| A549 | IC50 |
0.49 μM
Compound: 71
|
Inhibition of p97 ATPase in human A549 cells assessed as reduction in p62 protein incubated for 6 hrs by immunofluorescence assay
Inhibition of p97 ATPase in human A549 cells assessed as reduction in p62 protein incubated for 6 hrs by immunofluorescence assay
|
[PMID: 26565666] |
| A549 | IC50 |
0.68 μM
Compound: 71
|
Cytotoxicity against human A549 cells assessed as cell viability after 72 hrs by Celltiter-Glo assay
Cytotoxicity against human A549 cells assessed as cell viability after 72 hrs by Celltiter-Glo assay
|
[PMID: 26565666] |
| A549 | IC50 |
0.68 μM
Compound: 71
|
Inhibition of p97 ATPase in human A549 cells assessed as accumulation of K48 poly-ubiquitinated proteins incubated for 6 hrs by immunofluorescence assay
Inhibition of p97 ATPase in human A549 cells assessed as accumulation of K48 poly-ubiquitinated proteins incubated for 6 hrs by immunofluorescence assay
|
[PMID: 26565666] |
| A549 | IC50 |
1.03 μM
Compound: 71
|
Inhibition of p97 ATPase in human A549 cells assessed as accumulation of CHOP poly-ubiquitinated proteins incubated for 6 hrs by immunofluorescence assay
Inhibition of p97 ATPase in human A549 cells assessed as accumulation of CHOP poly-ubiquitinated proteins incubated for 6 hrs by immunofluorescence assay
|
[PMID: 26565666] |
| A549 | IC50 |
1.3 μM
Compound: CB-5083
|
Antiproliferative activity against human A549 cells after 72 hrs by CCK-8 assay
Antiproliferative activity against human A549 cells after 72 hrs by CCK-8 assay
|
[PMID: 30606672] |
| A549 | IC50 |
1.7 μM
Compound: CB-5083
|
Cytotoxicity against human A549 cells assessed as reduction in cell viability incubated for 72 hrs by CCK8 assay
Cytotoxicity against human A549 cells assessed as reduction in cell viability incubated for 72 hrs by CCK8 assay
|
[PMID: 33831696] |
| MIA PaCa-2 | EC50 |
0.146 μM
Compound: 4b
|
Antiproliferative activity against human MIAPaCa2 cells
Antiproliferative activity against human MIAPaCa2 cells
|
[PMID: 30830772] |
| RPMI-8226 | IC50 |
0.8 μM
Compound: CB-5083
|
Cytotoxicity against human RPMI-8226 cells assessed as reduction in cell viability incubated for 72 hrs by CCK8 assay
Cytotoxicity against human RPMI-8226 cells assessed as reduction in cell viability incubated for 72 hrs by CCK8 assay
|
[PMID: 33831696] |
| U-87MG ATCC | IC50 |
75.19 nM
Compound: CB5083
|
Cytotoxicity against human U87 cells assessed as reduction in cell viability incubated for 72 hrs by cell titer-glo luminescent assay
Cytotoxicity against human U87 cells assessed as reduction in cell viability incubated for 72 hrs by cell titer-glo luminescent assay
|
[PMID: 36634454] |
CB-5083 exhibits terminal elimination half-life (T1/2=2.56 h), moderate oral bioavailability (mouse 41%) and Cmax (mouse 7.95 μM) following oral administration (25 mg/kg) in female nude mice[1].
CB-5083 exhibits terminal elimination half-life (T1/2=2.83 h) due to high plasma clearance (5.9 mL/min/kg respectively) combined with large volumes of distribution (418 mL/kg respectively) following intravenous administration (3.0 mg/kg) in female nude mice[1].
CB-5083 has good metabolic stability with a 102 min T1/2 in a mouse liver microsomal stability study and a 172 min T1/2 in a hepatocyte stability study[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Animal Model:Nu/Nu nude female mice bearing established human tumor xenografts derived from HCT 116 colon[1]
-
Dosage:75 mg/kg
-
Administration:Administered orally using every day (qd) dosing, for 2 weeks.
-
Result:Showed more profound antitumor activity.
| NCT Number | Sponsor | Condition | Start Date |
Phase
|
|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
-
CAS No. 1542705-92-9
-
Appearance Solid
-
Molecular Weight 413.47
-
Formula C24H23N5O2
-
Color White to light yellow
-
SMILES
O=C(C1=CC=CC2=C1C=C(C)N2C3=NC(NCC4=CC=CC=C4)=C(COCC5)C5=N3)N
-
Shipping
Room temperature in continental US; may vary elsewhere.
-
Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Publications (48)
-
Journal Impact Factor
-
Most Recent
-
Signal Transduct Target Ther
VCP downstream metabolite glycerol-3-phosphate (G3P) inhibits CD8+T cells function in the HCC microenvironment. [Abstract]2025 Jan 24;10(1):26. PMID: 39848960
CB-5083 purchased from MedChemExpress. Usage Cited in: Signal Transduct Target Ther. 2025 Jan 24;10(1):26. [Abstract]
CB-5083 (0-2 μM; 24 h). Immunoblot analysis of the indicated proteins in HCCLM3 cells treated with gradient concentrations of CB-5083 or Vehicle for 24 h.
CB-5083 purchased from MedChemExpress. Usage Cited in: Signal Transduct Target Ther. 2025 Jan 24;10(1):26. [Abstract]
CB-5083 (50 mg/kg; oral gavage). Hepa1-6 tumors were dissected from the C57BL/6 mice treated with vehicle, CB-5083, aPD1, or both.
CB-5083 purchased from MedChemExpress. Usage Cited in: Signal Transduct Target Ther. 2025 Jan 24;10(1):26. [Abstract]
CB-5083 (50 mg/kg; oral gavage). The percentage of CD8+T cells in Hepa1-6 tumors were measured by flow cytometry analysis.
-
Nature
2025 Feb;638(8050):519-527. PMID: 39880951 -
Cell
2020 Dec 10;183(6):1714-1731.e10. PMID: 33275901 -
Mol Cell
UbiREAD deciphers proteasomal degradation code of homotypic and branched K48 and K63 ubiquitin chains. [Abstract]2025 Mar 20:S1097-2765(25)00152-2. PMID: 40132582 -
Mol Cell
CRL3ARMC5 ubiquitin ligase and Integrator phosphatase form parallel mechanisms to control early stages of RNA Pol II transcription. [Abstract]2024 Dec 5:S1097-2765(24)00949-3. PMID: 39667934 -
ACS Nano
Emerging of Ultrafine Membraneless Organelles as the Missing Piece of Nanostress: Mechanism of Biogenesis and Implications at Multilevels. [Abstract]2025 Feb 11;19(5):5659-5679. PMID: 39882824 -
Nat Commun
Human iPSC-based Modeling of Pulmonary Fibrosis Reveals p300/CBP Inhibition Suppresses Alveolar Transitional Cell State. [Abstract]2026 Feb 12;17(1):1214. PMID: 41680175 -
Nat Commun
2025 Dec 12;16(1):11092. PMID: 41387436
CB-5083 purchased from MedChemExpress. Usage Cited in: Nat Commun. 2025 Dec 12;16(1):11092. [Abstract]
Western blotting analysis of RKIP expression in HeLa cells treated with PA, PA plus CB-5083 (2.5 μM) or Vehicle for 12 hrs.
-
Nat Commun
Coronaviral nsp6 hijacks ERAD machinery to facilitate lipolysis and supply membrane components for DMV growth. [Abstract]2025 Nov 18;16(1):10094. PMID: 41253842 -
Nat Commun
Nanomaterial signatures program biomolecular condensates via triphasic separation for chemoplasticity remodeling. [Abstract]2025 Oct 29;16(1):9554. PMID: 41162367 -
Nat Commun
Proteasomes accumulate in the plant apoplast where they participate in microbe-associated molecular pattern (MAMP)-triggered pathogen defense. [Abstract]2025 Feb 14;16(1):1634. PMID: 39952938 -
Nat Commun
Coordination of transcription-coupled repair and repair-independent release of lesion-stalled RNA polymerase II. [Abstract]2024 Aug 17;15(1):7089. PMID: 39154022 -
Neuron
2025 Aug 29:S0896-6273(25)00587-2. PMID: 40902597 -
Adv Sci (Weinh)
Oncogenic Roles of Laminin Subunit Gamma-2 in Intrahepatic Cholangiocarcinoma via Promoting EGFR Translation. [Abstract]2024 Jun;11(21):e2309010. PMID: 38526177 -
Nat Chem Biol
2023 Dec;19(12):1513-1523. PMID: 37653169 -
Leukemia
Functional cooperativity of p97 and histone deacetylase 6 in mediating DNA repair in mantle cell lymphoma cells. [Abstract]2019 Jul;33(7):1675-1686. PMID: 30664664
CB-5083 purchased from MedChemExpress. Usage Cited in: Leukemia. 2019 Jul;33(7):1675-1686. [Abstract]
CB-5083 (0-2 μM; 6 h). Jeko-1 and Z138C cells are exposed to the indicated concentrations of CB-5083 and ACY-1215 in the presence or absence of the autophagy inhibitor chloroquine for 6 h and LC3B-II and p62 expression is assessed by immunoblot analysis.
-
Exp Mol Med
2025 Jun;57(6):1308-1323. PMID: 40583061 -
Sci Adv
Regulation of Wnt/PCP signaling through p97/VCP-KBTBD7-mediated Vangl ubiquitination and endoplasmic reticulum-associated degradation. [Abstract]2021 May 14;7(20):eabg2099. PMID: 33990333 -
J Immunother Cancer
2025 Nov 19;13(11):e012652. PMID: 41260904 -
Cell Death Dis
VCP enhances autophagy-related osteosarcoma progression by recruiting USP2 to inhibit ubiquitination and degradation of FASN. [Abstract]2024 Nov 3;15(11):788. PMID: 39489738 -
Proc Natl Acad Sci U S A
CRISPR screens identify the ATPase VCP as a druggable therapeutic vulnerability in cholangiocarcinoma. [Abstract]2025 Sep 30;122(39):e2519568122. PMID: 40991439 -
Biomed Pharmacother
Exploring in vivo combinatorial chemo-immunotherapy: Addressing p97 suppression and immune reinvigoration in pancreatic cancer with tumor microenvironment-responsive nanoformulation. [Abstract]2024 Jun:175:116660. PMID: 38701563 -
Cell Rep
p97/VCP inhibition causes excessive MRE11-dependent DNA end resection promoting cell killing after ionizing radiation. [Abstract]2021 May 25;35(8):109153. PMID: 34038735 -
-
Pharmaceutics
Functional pH-Responsive Nanoparticles for Immune Reprogramming in MSS Colorectal Cancer via ER Stress-Induced Proteostasis Disruption, PD-L1-Targeting miRNA, and TLR7 Activation. [Abstract]2025 Nov 20;17(11):1503. PMID: 41304839 -
Mol Ther Oncolytics
A Cereblon Modulator CC-885 Induces CRBN- and p97-Dependent PLK1 Degradation and Synergizes with Volasertib to Suppress Lung Cancer. [Abstract]2020 Jun 23;18:215-225. PMID: 32728610 -
Inflammation
2024 Oct;47(5):1868-1883. PMID: 38563877 -
PLoS Pathog
The protein segregase VCP/p97 promotes host antifungal defense via regulation of SYK activation. [Abstract]2024 Oct 29;20(10):e1012674. PMID: 39471181 -
Int J Mol Sci
2024 Aug 20;25(16):9022. PMID: 39201707 -
Mol Oncol
Raphin-1 mediates the survival and sensitivity to radiation of pediatric-type diffuse high-grade glioma via phosphorylated eukaryotic initiation factor 2α-dependent and -independent processes. [Abstract]2025 Jul 9. PMID: 40632659 -
FASEB J
FAT1 Enhances the Sensitivity of Non-Small Cell Lung Cancer to VCP Inhibitors by Regulating the Activation of the Endoplasmic Reticulum Stress Pathway. [Abstract]2025 May 15;39(9):e70585. PMID: 40293794 -
J Biol Chem
A technique for delineating the unfolding requirements for substrate entry into retrotranslocons during endoplasmic reticulum-associated degradation. [Abstract]2019 Dec 27;294(52):20084-20096. PMID: 31748412 -
J Virol
Unconventional p97/VCP-Mediated Endoplasmic Reticulum-to-Endosome Trafficking of a Retroviral Protein. [Abstract]2021 Jun 24;95(14):e0053121. PMID: 33952644 -
J Virol
A putative amphipathic alpha helix in hepatitis B virus small envelope protein plays a critical role in the morphogenesis of subviral particles. [Abstract]2021 Mar 25;95(8):e02399-20. PMID: 33536177 -
Biochim Biophys Acta Gene Regul Mech
2023 Jun;1866(2):194937. PMID: 37084817 -
Mol Biol Cell
Valosin-containing protein p97 extracts capping protein CP110 from the mother centriole to promote ciliogenesis. [Abstract]2025 Jan 9:mbcE24100455. PMID: 39785673 -
PLoS One
Interactome analysis of Bag-1 isoforms reveals novel interaction partners in endoplasmic reticulum-associated degradation. [Abstract]2021 Aug 24;16(8):e0256640. PMID: 34428256 -
Biochem Biophys Res Commun
Cereblon modulator CC-885 induces CRBN-dependent ubiquitination and degradation of CDK4 in multiple myeloma. [Abstract]2021 Apr 16:549:150-156. PMID: 33676183 -
bioRxiv
Nuclear tau aggregates inhibit RNA export and form by secondary seeding from cytosolic tau aggregates. [Abstract]2026 Feb 18:2026.02.17.706203. PMID: 41756918 -
-
-
-
-
-
-
-
Res Sq
DAF-16/FOXO and HLH-30/TFEB comprise a cooperative regulatory axis controlling tubular lysosome induction in C. elegans. [Abstract]2024 Mar 29:rs.3.rs-4049366. PMID: 38585786 -
Solvent & Solubility
DMSO : 100 mg/mL (241.86 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (6.05 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (6.05 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Please enter the basic information of animal experiments:
-
-
-
-
Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
-
%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
-
%+
-
+%Tween-80 + +
-
%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation
-
Data Sheet (279 KB)
-
SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
-
Handling Instructions (2659 KB)
References
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.4186 mL | 12.0928 mL | 24.1856 mL | 60.4639 mL |
| 5 mM | 0.4837 mL | 2.4186 mL | 4.8371 mL | 12.0928 mL | |
| 10 mM | 0.2419 mL | 1.2093 mL | 2.4186 mL | 6.0464 mL | |
| 15 mM | 0.1612 mL | 0.8062 mL | 1.6124 mL | 4.0309 mL | |
| 20 mM | 0.1209 mL | 0.6046 mL | 1.2093 mL | 3.0232 mL | |
| 25 mM | 0.0967 mL | 0.4837 mL | 0.9674 mL | 2.4186 mL | |
| 30 mM | 0.0806 mL | 0.4031 mL | 0.8062 mL | 2.0155 mL | |
| 40 mM | 0.0605 mL | 0.3023 mL | 0.6046 mL | 1.5116 mL | |
| 50 mM | 0.0484 mL | 0.2419 mL | 0.4837 mL | 1.2093 mL | |
| 60 mM | 0.0403 mL | 0.2015 mL | 0.4031 mL | 1.0077 mL | |
| 80 mM | 0.0302 mL | 0.1512 mL | 0.3023 mL | 0.7558 mL | |
| 100 mM | 0.0242 mL | 0.1209 mL | 0.2419 mL | 0.6046 mL |