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.
CB-5083 Chemical Structure
CAS No. : 1542705-92-9
This product is a controlled substance and not for sale in your territory.
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.
Powered by Bioz
See more details on Bioz
Description
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[1].
IC50 & Target
IC50: 11 nM (p97)[1]
In Vitro
CB-5083 shows cell killing potency with IC50s of 0.68, 0.68, 1.03, and 0.49 μM for lung carcinoma A549 CTG, A549 K48, A549 CHOP, and A549 p62, respectively[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
CB-5083 Related Antibodies
In Vivo
CB-5083 (75 mg/kg; oral administration; qd; for 2 weeks) shows antitumor activity in an HCT 116 tumor xenograft model[1].
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.
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
Solvent & Solubility
In Vitro:
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)
Preparing Stock Solutions
ConcentrationSolventMass
1 mg
5 mg
10 mg
1 mM
2.4186 mL
12.0928 mL
24.1856 mL
5 mM
0.4837 mL
2.4186 mL
4.8371 mL
10 mM
0.2419 mL
1.2093 mL
2.4186 mL
View the 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.
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.
Protocol 1
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 μLDMSO 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.
Protocol 2
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 μLDMSO 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.
Protocol 3
Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.5 mg/mL (6.05 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (25.0 mg/mL) to 900 μLCorn oil, and mix evenly.
For the following dissolution methods, please prepare the working solution directly.
It is recommended to prepare fresh solutions and use them promptly within a short period of time. 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.
Protocol 1
Add each solvent one by one: 50% PEG300 50% Saline
Solubility: 10 mg/mL (24.19 mM); Clear solution; Need ultrasonic
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
Dosage
mg/kg
Animal weight (per animal)
g
Dosing volume (per animal)
μL
Number of animals
Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO+
%
+
%
Tween-80
+
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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).
Calculation results:
Working solution concentration:
mg/mL
Method for preparing stock solution:
mg
drug dissolved in
μL
DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take
μL DMSO stock solution, add
μL .
μL , mix evenly, next add
μL Tween 80, mix evenly, then add
μL Saline.
Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution
If the continuous dosing period exceeds half a month, please choose this protocol carefully.
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.
[1]. Zhou HJ, et al. Discovery of a First-in-Class, Potent, Selective, and Orally Bioavailable Inhibitor of the p97 AAA ATPase (CB-5083). J Med Chem. 2015 Dec 24;58(24):9480-97.
[Content Brief]
[1]. Zhou HJ, et al. Discovery of a First-in-Class, Potent, Selective, and Orally Bioavailable Inhibitor of the p97 AAA ATPase (CB-5083). J Med Chem. 2015 Dec 24;58(24):9480-97.
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
ConcentrationSolventMass
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
CB-5083 Related Classifications
Help & FAQs
Do most proteins show cross-species activity?
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.