tcsc3298 PNU-159682

PNU-159682, a highly potent metabolite of the anthracycline nemorubicin with outstanding cytotoxicity, is a potent ADCs cytotoxin.

In Vitro: PNU-159682 inhibits a panel of human tumor cell lines with IC₇₀ values in the range of 0.07-0.58 nM, and is 2,360- to 790-fold and 6,420- to 2,100-fold more potent than MMDX and doxorubicin, respectively^[1]. PNU-159682 (100 μM) weakly inhibits topoisomerase II unknotting activity. PNU-159682 (10 μM)-DNA adducts contain one or two drug molecules bound to double-stranded DNA^[2]. PNU-159682 shows cytotoxic effect on CAIX-expressing SKRC-52 cells with IC₅₀ of 25 nM^[3].

In Vivo: PNU-159682 (15 μg/kg, i.v.) shows antitumor activity in mice bearing disseminated murine L1210 leukemia and in MX-1 human mammary carcinoma xenografts at 4 μg/kg^[1]. PNU-159682 (25 nmol/kg) exhibits a potent antitumor effect in mice bearing SKRC-52 xenografted tumors^[3].