Dxd Chemical Properties

Boiling point:

957.9±65.0 °C(Predicted)

Density 

1.57±0.1 g/cm3(Predicted)

storage temp. 

Store at -20°C

solubility 

DMSO:40.0(Max Conc. mg/mL);81.06(Max Conc. mM)

form 

Solid

pka

11.18±0.40(Predicted)

Dxd Usage And Synthesis

Biological Activity

Dxd (Exatecan derivative for ADC) is a potent DNA topoisomerase I inhibitor with IC50 value of 0.31 μM, which can be used as a payload for an antibody-drug conjugate ADC (DS-8201a) targeting HER2.

in vitro

Dxd (Exatecan derivative for ADC) is a potent DNA topoisomerase I inhibitor, with an IC 50 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 IC 50 s 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 IC 50 values of 26.8, 25.4, and 6.7 ng/mL, respectively, but with no such inhibition on MDA-MB-468 (IC 50 , >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.