CB-5083

Catalog No.S8101 Batch:S810102

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Technical Data

Formula

C24H23N5O2
Molecular Weight 413.47 CAS No. 1542705-92-9
Solubility (25°C)* In vitro DMSO 82 mg/mL (198.32 mM)
Ethanol 29 mg/mL (70.13 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description CB-5083 is a potent, selective, and orally bioavailable p97 AAA ATPase inhibitor with IC50 of 11 nM. Phase 1.
Targets
p97 AAA ATPase [1]
(Cell-free assay)
11 nM
In vitro In A549 cells, CB-5083 causes significant K48 poly-ubiquitinated protein and CHOP accumulation as well as p62 reduction, and kills tumor cells with IC50 of 680 nM. [1]
In vivo In mice bearing human HCT 116 colon tumor xenografts, CB-5083 (75 mg/kg, p.o.) significantly inhibits tumor growth. In mice bearing established human AMO-1 multiple myeloma and A549 lung carcinoma tumor xenografts, CB-5083 (100 mg/kg, p.o.) also results in significant tumor growth inhibition. [1]

Protocol (from reference)

Kinase Assay:[1]
  • ATPase assay

    Compounds are diluted in DMSO with a 3-fold 10-point serial dilution starting at 10 μM. The assay is done in a 384-well plate with each row as a single dilution series with duplicate of each compound concentration point. In 5 μL total volume, 20 nM p97 hexameric enzyme and 20 μM ATP are added to start the reaction. The plate is sealed and incubated at 37 °C for 15 min after mixing thoroughly in an orbital shaker. Compound dilution, ATP and enzymes addition are conducted with automated liquid handling using the Freedom Evo. ADP Glo reagents 1 and 2 are added according to the manufacturer’s protocol. The luminescence is measured by Envision plate reader as the end point of the reaction. The IC50 of each compound is derived by fitting the luminescence values to a four-parameter sigmoidal curve.
Cell Assay:[1]
  • Cell lines

    A549 cells

  • Concentrations

    ~40.0 μM

  • Incubation Time

    72 h

  • Method

    A549 and other tumor cell lines are cultured according to ATCC guidelines. Cells are cultured in black or white, clear-bottomed, tissue culture-treated 384-well plates. Cells are treated with 10-point dose titration of the compound in well duplicates. After a 72 h treatment, CellTiter-Glo is added to the white plates to measure cell viability. Luminescence values are fit to a four-parameter sigmoidal curve to determine IC50 concentrations.
Animal Study:[1]
  • Animal Models

    Nu/Nu nude female mice bearing human HCT 116 colon tumor xenografts

  • Dosages

    75 mg/kg, qd

  • Administration

    p.o.

Customer Product Validation

Data from [Data independently produced by , , Cancer Res, 2018, 78(14):3809-3822]

Data from [Data independently produced by , , Mol Oncol, 2016, 10(10):1559-1574]

Data from [Data independently produced by , , Mol Cell Proteomics, 2018, 17(7):1295-1307]

Selleck's CB-5083 has been cited by 49 publications

TEX264 drives selective autophagy of DNA lesions to promote DNA repair and cell survival [ Cell, 2024, 187(20):5698-5718.e26] PubMed: 39265577
Endogenous aldehyde-induced DNA-protein crosslinks are resolved by transcription-coupled repair [ Nat Cell Biol, 2024, 10.1038/s41556-024-01401-2] PubMed: 38600234
Alternating binding and p97-mediated dissociation of SDS22 and I3 recycles active PP1 between holophosphatases [ Proc Natl Acad Sci U S A, 2024, 121(36):e2408787121] PubMed: 39207734
hnRNPA2B1 represses the disassembly of arsenite-induced stress granules and is essential for male fertility [ Cell Rep, 2024, 43(2):113769] PubMed: 38363675
Targeting VCP potentiates immune checkpoint therapy for colorectal cancer [ Cell Rep, 2023, 42(11):113318] PubMed: 37865914
The FAM104 proteins VCF1/2 promote the nuclear localization of p97/VCP [ Elife, 2023, 12e92409] PubMed: 37713320
The generation of detergent-insoluble clipped fragments from an ERAD substrate in mammalian cells [ Sci Rep, 2023, 13(1):21508] PubMed: 38057493
Quantitative measurement of the requirement of diverse protein degradation pathways in MHC class I peptide presentation [ Sci Adv, 2023, 9(25):eade7890] PubMed: 37352349
Multi-omic Phenotype Discovery for Mendelian Disease Variants [ Molecular Genetics University of Toronto , 2023, ] PubMed: none
VCP/p97, a pleiotropic protein regulator of the DNA damage response and proteostasis, is a potential therapeutic target in KRAS-mutant pancreatic cancer [ Genes Cancer, 2023, 14:30-49] PubMed: 36923647

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.