Edotecarin

608.55282

608.55

1V8X590XDP

C2665

241

-0.7

1.96±0.1 g/cm3(Predicted)

330° (dec)

1047.5±75.0 °C(Predicted)

D23 +117° (c = 0.8 in 1:1 acetonitrile/water)

Clinical studies with edotecarin have shown activity in subjects with colorectal cancer, esophageal cancer and other solid tumors.

Edotecarin, formerly J-107088 is a novel, non-camptothecin, DNA topoisomerase-1 inhibitor. It is part of the class of compounds called indolocarbazoles. It is a novel inhibitor of topoisomerase I that induces single-strand DNA cleavage more effectively than NB-506 or camptothecin (CPT) and at different DNA sequences. The DNA-topoisomerase I complexes induced by edotecarin are more stable than those occurring after exposure to CPT or NB-506. The antitumor activity of edotecarin is less cell cycle dependent than other topoisomerase I inhibitors. Being an indolocarbazole, it is structurally related to staurosporine but does not possess protein kinase inhibitory properties. The antitumor activity of edotecarin has been tested in vitro and in vivo, and inhibition of tumor growth has been observed in breast, cervix, pharynx, lung, prostate, colon, gastric, and hepatic cancer models. Edotecarin is effective on cells that have acquired resistance related to P-glycoprotein. In vitro synergy has been demonstrated when edotecarin was tested in combination with cisplatin, 5-fluorouracil, etoposide, paclitaxel, doxorubicin, vincristine, CPT, and gemcitabine.

Edotecarin does not form active metabolites and is not a substrate for in vitro P450-mediated metabolism.

20 to 25 hours

Edotecarin inhibits the enzyme topoisomerase I through stabilization of the DNA-enzyme complex and enhanced single-strand DNA cleavage, resulting in inhibition of DNA replication and decreased tumor cell proliferation.

12-beta-D-glucopyranosyl-12,13-dihydro-2,10-dihydroxy-6-((2-hydroxy-1-(hydroxymethyl)ethyl)amino)-5H-indolo(2,3-a)pyrrolo(3,4-c)carbazole-5,7(6H)-dione