CB-5083

製品コードS8101 バッチS810102

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C24H23N5O2
分子量 413.47 CAS No. 1542705-92-9
Solubility (25°C)* 体外 DMSO 82 mg/mL (198.32 mM)
Ethanol 29 mg/mL warmed with 50ºC water bath (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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 CB-5083 is a potent, selective, and orally bioavailable p97 AAA ATPase inhibitor with IC50 of 11 nM. Phase 1.
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]

プロトコル(参考用のみ)

キナーゼアッセイ 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.
細胞アッセイ 細胞株 A549 cells
濃度 ~40.0 μM
反応時間 72 h
実験の流れ 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.
動物実験 動物モデル Nu/Nu nude female mice bearing human HCT 116 colon tumor xenografts
投薬量 75 mg/kg, qd
投与方法 p.o.

カスタマーフィードバック

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の高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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
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
The ubiquitin-dependent ATPase p97 removes cytotoxic trapped PARP1 from chromatin [ Nat Cell Biol, 2022, 24(1):62-73] PubMed: 35013556
The ubiquitin-dependent ATPase p97 removes cytotoxic trapped PARP1 from chromatin [ Nat Cell Biol, 2022, 24(1):62-73] PubMed: 35013556
TOLLIP-mediated autophagic degradation pathway links the VCP-TMEM63A-DERL1 signaling axis to triple-negative breast cancer progression [ Autophagy, 2022, 1-17] PubMed: 35920704
A drug repurposing strategy for overcoming human multiple myeloma resistance to standard-of-care treatment [ Cell Death Dis, 2022, 13(3):203] PubMed: 35246527

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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