Dxd

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).

Product information

CAS Number: 1599440-33-1

Molecular Weight: 493.48

Formula: C26H24FN3O6

Synonym:

Exatecan derivative for ADC

Chemical Name: N-[(10S, 23S)-10-ethyl-18-fluoro-10-hydroxy-19-methyl-5, 9-dioxo-8-oxa-4, 15-diazahexacyclo[14.7.1.0, .0, .0, .0, ]tetracosa-1, 6(11), 12, 14, 16, 18, 20(24)-heptaen-23-yl]-2-hydroxyacetamide

Smiles: CC1C2CC[C@H](NC(=O)CO)C3=C4CN5C(=CC6=C(COC(=O)[C@]6(O)CC)C5=O)C4=NC(=CC=1F)C3=2

InChiKey: PLXLYXLUCNZSAA-QLXKLKPCSA-N

InChi: InChI=1S/C26H24FN3O6/c1-3-26(35)15-6-19-23-13(8-30(19)24(33)14(15)10-36-25(26)34)22-17(28-20(32)9-31)5-4-12-11(2)16(27)7-18(29-23)21(12)22/h6-7,17,31,35H,3-5,8-10H2,1-2H3,(H,28,32)/t17-,26-/m0/s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

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

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

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).

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.

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.

Products are for research use only. Not for human use.