Date Modified: 2024-01-02 12:51:44
Structure
Common Name: Dxd
Dxd Structure:
CAS Number: N/A
Molecular Weight: 493.48
Density: N/A
Boiling Point: N/A
Molecular Formula: C26H24FN3O6
Melting Point: N/A
MSDS: N/A
Flash Point: N/A
Use of Dxd: Dxd is an antibody-drug conjugate (ADC) that targets the HER2 protein. As a potent DNA topoisomerase I inhibitor with an IC50 of 0.31 μM, it is often used as a conjugated drug in cancer treatments.
Names and Biological Activity:
Dxd is a name for a specific molecule that acts as an antibody-drug conjugate (ADC) targeting the HER2 protein. It is a potent DNA topoisomerase I inhibitor with an IC50 of 0.31 μM, which allows it to selectively target and inhibit the activity of the HER2 protein without causing harm to surrounding cells or tissues. This makes it a valuable tool in treating certain types of cancer, particularly those involving the HER2 gene. The related catalog entry "ADC Cytotoxin" provides more information on this type of treatment.
xd is a DNA topoisomerase I inhibitor, with an IC50 of 0.31 μM. It is used as the conjugated drug for HER2-targeting antibody-drug conjugate (ADC) called DS-8201a. Dxd exhibits cytotoxic effects on human cancer cell lines like KPL-4, NCI-N87, SK-BR-3, and MDA-MB-468, with IC50 values ranging from 1.43 nM to 4.07 nM. However, when used as the payload in IgG-ADC (DS-8201a), it fails to show any inhibition on these four cell lines, even when they expressHER2.
On the other hand, DS-8201a (with Dxd as the payload) shows significant suppression on HER2-positive cell lines such as KPL-4, NCI-N87, and SK-BR-3, with IC50 values ranging from 26.8 ng/mL to 6.7 ng/mL. In contrast, no such inhibition was observed in MDA-MB-468 cells, which have an IC50 value of over 10,000 ng/mL[1].
In vivo studies have also demonstrated that DS-8201a (with Dxd as the payload of 10 mg/kg, i.v.) has potent antitumor activity against HER2-positive models like KPL-4, JIMT-1, and Capan-1 cells. Furthermore, it showed efficacy in reducing tumor growth in HER2 low-expressing ST565 and ST313 models where HER2 IHC expression was 1+ and FISH results were negative[1].
Overall, DS-8201a (Dxd is the payload) is a promising drug candidate for treating HER2-positive cancers due to its strong antitumor activity in vitro and in vivo.
In the present study, we describe a strategy for the in vivo detection of ds-8201a-mediated downregulation of HER2/neu by using the luciferase reporter gene Dxd. First, cells were seeded to a 96-well plate at 1,000 cells per well. After overnight incubation, Dxd was added. Cell viability was evaluated after 6 days using a CellTiter-Glo Luminescent Cell Viability Assay. For the detection of HER2 expression in each cell line, cells were incubated on ice for 30 minutes with FITC Mouse IgG1, κ Isotype Control, or anti-HER2/neu FITC. After washing, the labeled cells were analyzed by FACSCalibur. Relative mean fluorescence intensity (rMFI) was calculated[1].
Animal Administration
Mice [1] Briefly, each cell suspension or tumor fragment was inoculated subcutaneously into specific pathogen-free female nude mice. When the tumor had grown to an appropriate volume, the tumor-bearing mice were randomized into treatment and control groups based on the tumor volumes, and dosing was initiated on day 0. Each substance (DS-8201a, 1 or 10 mg/kg, i.v.; Dxd is the payload) was administered intravenously to the mice. Tumor growth inhibition (TGI,%) was calculated[1].
Chemical and Physical Properties: The molecular formula for this substance is C26H24FN3O6.
Molecular Weight: This has a molecular weight of 493.48.
Storage Condition: The recommended storage condition is 2-8°C.
