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 (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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

493.48

C₂₆H₂₄FN₃O₆

1599440-33-1

Room temperature in continental US; may vary elsewhere.

-20°C, stored under nitrogen

*In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)

In Vitro: 

DMSO : 7.14 mg/mL (14.47 mM; Need ultrasonic)

*

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；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month (stored under nitrogen)。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: 0.71 mg/mL (1.44 mM); Suspended solution; Need ultrasonic

  此方案可获得 0.71 mg/mL (1.44 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。

  以 1 mL 工作液为例，取 100 μL 7.1 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• 2.

  请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

  Solubility: ≥ 0.71 mg/mL (1.44 mM); Clear solution

  此方案可获得 ≥ 0.71 mg/mL (1.44 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 7.1 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
• 3.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 0.71 mg/mL (1.44 mM); Clear solution

  此方案可获得 ≥ 0.71 mg/mL (1.44 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 7.1 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [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.

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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [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.