Dxd NEW

Dxd

Modify Date: 2024-01-02 12:51:44

Dxd structure	Common Name	Dxd
	CAS Number	1599440-33-1	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

Purity		Quantity		Budget		Inquiry

Use of Dxd Dxd 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).

• Properties

• Spectrum

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 Names

Name	Dxd

 Dxd Biological Activity

Description	Dxd 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).
Related Catalog	Signaling Pathways >> Antibody-drug Conjugate >> ADC Cytotoxin Research Areas >> Cancer
Target	Topoisomerase I:0.31 μM (IC50)
In Vitro	Dxd 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].
Cell Assay	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].
Animal Admin	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].
References	[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.

 Chemical & Physical Properties

Molecular Formula	C26H24FN3O6
Molecular Weight	493.48
Storage condition	2-8℃

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