| Identification | Back Directory | [Name]
Dxd | [CAS]
1599440-33-1 | [Synonyms]
Dxd
Exatecan derivative
Exatecan derivative for ADC
N-[(1S,9S)-9-Ethyl-5-fluoro-2,3,9,10,13,15-hexahydro-9-hydroxy-4-methyl-10,13-dioxo-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl]-2-hydroxyacetamide
Acetamide, N-[(1S,9S)-9-ethyl-5-fluoro-2,3,9,10,13,15-hexahydro-9-hydroxy-4-methyl-10,13-dioxo-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl]-2-hydroxy- | [Molecular Formula]
C26H24FN3O6 | [MDL Number]
MFCD31657444 | [MOL File]
1599440-33-1.mol | [Molecular Weight]
493.48 |
| Chemical Properties | Back Directory | [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) | [color ]
Off-white to yellow |
| Hazard Information | Back Directory | [Uses]
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). | [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. | [IC 50]
Topoisomerase I: 0.31 μM (IC50); Camptothecins | [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. DOI:10.1158/1078-0432.CCR-15-2822 |
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