1599440-33-1
1599440-33-1 结构式
基本信息
DX-8951衍生物
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-
物理化学性质
常见问题列表
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Topoisomerase I 0.31 μM (IC 50 ) |
Camptothecins
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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).
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.