CB-5083 _p97 抑制劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemECB-5083Cat. No.: HY-12861CAS No.: 1542705-92-9分式: CHNO分量: 413.47作靶點: p97作通路: Cell Cycle/DNA Damage儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 100 mg/mL (241.86 mM)* means soluble, but s

2、aturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 2.4186 mL 12.0928 mL 24.1856 mL5 mM 0.4837 mL 2.4186 mL 4.8371 mL10 mM 0.2419 mL 1.2093 mL 2.4186 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。體內(nèi)實驗請根據(jù)您的實驗動物和給藥式選擇適當?shù)娜芙獍?，配制前請先配制澄清的儲備液，再依次添加助溶?為保證實驗結(jié)果的可靠性，體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當天使；澄清的儲備液可

3、以根據(jù)儲存條件，適當保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (6.05 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (6.05 mM); Clear solution3. 請依序添加每種溶劑： 10% DMSO 90% corn oil1/3 Master of Small Molecu

4、les 您邊的抑制劑師www.MedChemESolubility: 2.5 mg/mL (6.05 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 CB-5083有效，選擇性和有服活性的 p97 抑制劑，IC50 值為 11 nM。IC50 & Target IC50: 11 nM (p97) 1體外研究 Treatment of tumor cells with CB-5083 leads to significant accumulation of markers associated with inhibitionof ubiquitinprotea

5、some system and endoplasmic reticulum-associated degradation functions, which inducesirresolvable proteotoxic stress and cell death 1體內(nèi)研究 In tumor bearing mice, oral administration of CB-5083 causes rapid accumulation of markers of the unfoldedprotein response and subsequently induces apoptosis lead

6、ing to sustained antitumor activity in in vivoxenograft models of both solid and hematological tumors. CB-5083 has been taken into phase 1 clinical trialsin patients with multiple myeloma and solid tumors 1.PROTOCOLKinase Assay 1 The ATPase assay is performed to determine the IC50 value. compounds (

7、CB-5083) are diluted in DMSOwith a 3-fold 10-point serial dilution starting at 10 M. The assay is done in a 384-well plate with each row asa single dilutionMCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 1 A549 and other tumor cell lines are

8、cultured according to ATCC guidelines. Cells are cultured in black orwhite, clear-bottomed, tissue culture-treated 384-well plates. Cells are treated with 10-point dose titration ofthe compound (CB-5083) in well duplicates. After a 72 h treatment, CellTiter-Glo is added to the white platesto measure

9、 cell viability 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice: Tumor-bearing mice are used to evaluate pharmacokinetics and pharmacodynamics effect andAdministration 1 antitumor activity. Both molecules (CB-5083 and compoud 69) are admin

10、istered orally as a suspension in0.5% methylcellulose aqueous suspensions at the fixed dose strength of 150 mg/kg; plasma and tumorsamples at multiple time points (2, 6, 16, and 24 h) are harvested for pharmacokinetics andpharmacodynamics analysis 1.MCE has not independently confirmed the accuracy o

11、f these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻 Leukemia. 2019 Jul;33(7):1675-1686.See more customer validations on HYPERLINK / www.MedChemE2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEREFERENCES1. Zhou HJ, et al. Discovery of a First-in-Class, Potent, Selective, and Orally Bioavailable Inhibitor of the p97 AAA ATPase (CB-5083). JMed Chem. 2015 Dec 24;58(24):9480-97.McePdfHeightCaution: Product has