CB-5083 _p97 抑制剂 - 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作靶点: p97作通路: Cell Cycle/DNA Damage储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 100 mg/mL (241.86 mM)* means soluble, but s

2、aturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液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请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。体内实验请根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄清的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您现现配，当天使；澄清的储备液可

3、以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (6.05 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (6.05 mM); Clear solution3. 请依序添加每种溶剂： 10% DMSO 90% corn oil1/3 Master of Small Molecu

4、les 您边的抑制剂师www.MedChemESolubility: 2.5 mg/mL (6.05 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 CB-5083有效，选择性和有服活性的 p97 抑制剂，IC50 值为 11 nM。IC50 & Target IC50: 11 nM (p97) 1体外研究 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体内研究 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.户使本产品发表的科研献 Leukemia. 2019 Jul;33(7):1675-1686.See more customer validations on HYPERLINK / www.MedChemE2/3 Master of Small Molecules 您边的抑制剂师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