CB-5083

Alias: CB5083; CB-5083; CB 5083
Cat No.:V0181 Purity: ≥98%
CB-5083 is a novel, potent, selective, first in class and orally bioavailable p97 AAA ATPase inhibitor with potential anticancer activity.
CB-5083 Chemical Structure CAS No.: 1542705-92-9
Product category: ATM(ATR)
This product is for research use only, not for human use. We do not sell to patients.
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description

CB-5083 is a novel, potent, selective, first in class and orally bioavailable p97 AAA ATPase inhibitor with potential anticancer activity. Its IC50 value for p97 AAA ATPase inhibition is 11 nM. In hematological and solid models, CB-5083 exhibits antitumor activity and disturbs cellular protein homeostasis. After just one administration, CB-5083 causes poly-ubiquitin to accumulate quickly and persistently in tumor xenografts. Additionally, CB-5083 seems to be more potent than the proteasome inhibitors that are currently on the market, which supports the idea of targeting p97 and protein homeostasis in cancer treatment.

Biological Activity I Assay Protocols (From Reference)
Targets
p97 ( IC50 = 11 nM )
ln Vitro

In vitro activity: CB-5083 kills tumor cells with an IC50 of 680 nM in A549 cells by causing significant accumulation of K48 poly-ubiquitinated protein and CHOP, as well as mRNA reduction.[1]

ln Vivo
CB-5083 (75 mg/kg, p.o.) significantly inhibits tumor growth in mice containing human HCT 116 colon tumor xenografts. CB-5083 (100 mg/kg, p.o.) also significantly inhibits the growth of tumors in mice harboring established human AMO-1 multiple myeloma and A549 lung carcinoma tumor xenografts.[1]
Enzyme Assay
Starting at 10 μM, compounds are diluted in DMSO using a 3-fold 10-point serial dilution method. The assay is carried out in a 384-well plate, with duplicates of each compound concentration point in each row representing a single dilution series. To initiate the reaction, 20 μM ATP and 20 nM p97 hexameric enzyme are added in a total volume of 5 μL. Once the plate is well mixed in an orbital shaker, it is sealed and incubated for 15 minutes at 37 °C. Compound dilution, ATP addition, and enzyme addition are carried out with the Freedom Evo's automated liquid handling. As directed by the manufacturer, add ADP Glo reagents 1 and 2. As the reaction's end point, the luminescence is measured using an Envision plate reader. The luminescence values of each compound are fitted to a four-parameter sigmoidal curve in order to determine its IC50.
Cell Assay
The ATCC recommends that A549 and other tumor cell lines be cultured. Stem cells are grown in 384-well plates with a clear bottom and a black or white color. Compound is applied to cells in well duplicates using a 10-point dose titration. The cell viability of the white plates is measured by adding CellTiter-Glo after a 72-hour treatment. Finding IC50 concentrations involves fitting luminosity values to a four-parameter sigmoidal curve.
Animal Protocol
Suspended in 0.5% methylcellulose in water; 75 mg/kg, qd; oral administration
Nu/Nu nude female mice bearing human HCT 116 colon tumor xenografts
References

[1]. J Med Chem . 2015 Dec 24;58(24):9480-97.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C24H23N5O2
Molecular Weight
413.47
Exact Mass
413.19
Elemental Analysis
C, 69.72; H, 5.61; N, 16.94; O, 7.74
CAS #
1542705-92-9
Appearance
White to off-white solid powder
SMILES
CC1=CC2=C(C=CC=C2N1C3=NC4=C(COCC4)C(=N3)NCC5=CC=CC=C5)C(=O)N
InChi Key
RDALZZCKQFLGJP-UHFFFAOYSA-N
InChi Code
InChI=1S/C24H23N5O2/c1-15-12-18-17(22(25)30)8-5-9-21(18)29(15)24-27-20-10-11-31-14-19(20)23(28-24)26-13-16-6-3-2-4-7-16/h2-9,12H,10-11,13-14H2,1H3,(H2,25,30)(H,26,27,28)
Chemical Name
1-[4-(benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl]-2-methylindole-4-carboxamide
Synonyms
CB5083; CB-5083; CB 5083
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO: 83~100 mg/mL (200.7~241.9 mM)
Water: <1 mg/mL
Ethanol: ~13 mg/mL (~31.4 mM)
Solubility (In Vivo)
0.5%CMC Na+5%Tween 80: 30mg/mL
 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 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

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

Calculator

Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

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An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
  • Enter 350.26 in the Molecular Weight (MW) box
  • Enter 10 in the Concentration box and choose the correct unit (mM)
  • Enter 5 in the Volume box and choose the correct unit (mL)
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  • The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
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  • The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box
g/mol

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:
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Definitions of molecular mass, molecular weight, molar mass and molar weight:
  • Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
  • Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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Calculation results

Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
             (2) Be sure to add the solvent(s) in order.

Clinical Trial Information
NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT02223598 Terminated Drug: Dexamethasone
Drug: CB-5083
Relapsed and Refractory
Multiple Myeloma
Cleave Biosciences, Inc. August 25, 2014 Phase 1
NCT02243917 Terminated Drug: CB-5083 Advanced Solid Tumors Cleave Biosciences, Inc. October 11, 2014 Phase 1
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