Dxd-Exatecan-derivative-for-ADC-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEDxdCat. No.: HY-13631DCAS No.: 1599440-33-1Synonyms: Exatecan derivative for ADC分式: CHFNO分量: 493.48作靶点: Topoisomerase; ADC Cytotoxin作通路: Cell Cycle/DNA Damage; Antibody-drug Conjugate/ADCRelated储存式: Powder -20C 3 years4C 2 years

2、In solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 50 mg/mL (101.32 mM; Need ultrasonic)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.07 mM); Suspended solution; Need ultrasonic1/2 Master of Small Molecules 您边的抑制剂师www.MedChemEBIOLOGICAL ACTIVITY物活性 Dxd种有效的 DNA topoisomerase I 抑制剂

3、，IC50 值为 0.31 M，可作靶作于 HER2 的 抗体偶联药物 ADC (DS-8201a) 的有效载荷。IC50 & Target Topoisomerase I0.31 M (IC50)体外研究 Dxd is a potent DNA topoisomerase I inhibitor, with an IC50 of 0.31 M, used as a conjugated drug of HER2-targeting ADC (DS-8201a). Dxd is cytotoxic to human cancer cell lines of KPL-4, NCI-N87, SK

4、-BR-3, andMDA-MB-468 with IC50s of 1.43 nM-4.07 nM, but the control IgG-ADC (Dxd is the payload) shows noinhibition on the four cell lines (with HER2 expression). DS-8201a (Dxd is the payload) displays significantsuppression on the HER2-positive KPL-4, NCI-N87, and SK-BR-3 cell lines, with IC50 valu

5、es of 26.8, 25.4,and 6.7 ng/mL, respectively, but with no such inhibition on MDA-MB-468 (IC50, 10,000 ng/mL) 1.体内研究 DS-8201a (Dxd is the payload, 10 mg/kg, i.v.) shows potent antitumor activity in HER2-positive models withKPL4, JIMT-1, and Capan-1 and in HER2 low-expressing ST565 and ST313 models wi

6、th HER2 IHC1+/FISH-negative expression 1.PROTOCOLCell Assay 1 Cells are seeded to a 96-well plate at 1,000 cells per well. After overnight incubation, Dxd is added. Cellviability is evaluated after 6 days using a CellTiter-Glo Luminescent Cell Viability Assay. For the detection ofHER2 expression in

7、each cell line, cells are incubated on ice for 30 minutes with FITC Mouse IgG1, IsotypeControl, or anti-HER2/neu FITC. After washing, the labeled cells are analyzed by FACSCalibur. Relativemean fluorescence intensity (rMFI) is calculated 1.MCE has not independently confirmed the accuracy of these me

8、thods. They are for reference only.Animal Mice 1Administration 1 Briefly, each cell suspension or tumor fragment is inoculated subcutaneously into specific pathogen-freefemale nude mice. When the tumor has grown to an appropriate volume, the tumor-bearing mice arerandomized into treatment and contro

9、l groups based on the tumor volumes, and dosing is initiated on day 0.Each substance (DS-8201a, 1 or 10 mg/kg, i.v.; Dxd is the payload) is administered intravenously to themice. Tumor growth inhibition (TGI, %) is calculated 1.MCE has not independently confirmed the accuracy of these methods. They

10、are for reference only.REFERENCES1. Ogitani Y, et al. DS-8201a, A Novel HER2-Targeting ADC with a Novel DNA Topoisomerase I Inhibitor, Demonstrates a PromisingAntitumor Efficacy with Differentiation from T-DM1. Clin Cancer Res. 2016 Oct 15;22(20):5097-5108.McePdfHeightCaution: Product has not been fully valida