| CAS |
No.1599440-33-1 |
| 英文名称 |
Dxd |
| 分子式 |
C26H24FN3O6 |
| 分子量 |
493.48 |
| 溶解性 |
Soluble in DMSO ≥4mg/mL |
| 纯度 |
≥98% |
| 外观(性状) |
Off-white to light yellow Solid |
| 储存条件 |
Powder:2-8℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| 靶点 |
Topoisomerase |
| 通路 |
DNA Damage/DNA Repair |
| 背景说明 |
Dxd是一种有效的 DNA topoisomerase I 抑制剂。 |
| 生物活性 |
Dxd (Exatecan derivative for ADC) is a potent DNA topoisomerase I inhibitor， with an IC50 of 0.31 μM， used as a conjugated drug of HER2-targeting ADC (DS-8201a).[1] |
| In Vitro |
Dxd (Exatecan derivative for ADC) is a potent DNA topoisomerase I inhibitor， with an IC50 of 0.31 μM， 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-BR-3， and MDA-MB-468 with IC50s of 1.43 nM-4.07 nM， but the control IgG-ADC (Dxd is the payload) shows no inhibition on the four cell lines (with HER2 expression). DS-8201a (Dxd is the payload) displays significant suppression on the HER2-positive KPL-4， NCI-N87， and SK-BR-3 cell lines， with IC50 values 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]. |
| In Vivo |
DS-8201a (Dxd is the payload， 10 mg/kg， i.v.) shows potent antitumor activity in HER2-positive models with KPL4， JIMT-1， and Capan-1 and in HER2 low-expressing ST565 and ST313 models with HER2 IHC 1+/FISH-negative expression[1]. |
| 细胞实验 |
Cells are seeded to a 96-well plate at 1，000 cells per well. After overnight incubation， Dxd is added. Cell viability is evaluated after 6 days using a CellTiter-Glo Luminescent Cell Viability Assay. For the detection of HER2 expression in each cell line， cells are incubated on ice for 30 minutes with FITC Mouse IgG1， κ Isotype Control， or anti-HER2/neu FITC. After washing， the labeled cells are analyzed by FACSCalibur. Relative mean fluorescence intensity (rMFI) is calculated[1]. |
| 动物实验 |
Mice[1]Briefly， each cell suspension or tumor fragment is inoculated subcutaneously into specific pathogen-free female nude mice. When the tumor has grown to an appropriate volume， the tumor-bearing mice are randomized into treatment and control 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 the mice. Tumor growth inhibition (TGI， %) is calculated[1]. |
| 数据来源文献 |
[1]. Ogitani Y， et al. DS-8201a， A Novel HER2-Targeting ADC with a Novel DNA Topoisomerase I Inhibitor， Demonstrates a Promising Antitumor Efficacy with Differentiation from T-DM1. Clin Cancer Res. 2016 Oct 15;22(20):5097-5108. |
| 规格 |
1mg 5mg 10mg 50mg 100mg |
| 单位 |
瓶 |
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