202350-68-3
基本信息
(8S,10S)-7,8,9,10-四氫-6,8,11-三羥基-8-(2-羥基乙酰基)-1-甲氧基-10-[[(1S,3R,4AS,9S,9AR,10AS)-八氫-9-甲氧基-1-甲基-1H-吡喃并[4',3':4,5]惡唑并[2,3-C][1,4]惡嗪-3-基]氧基] - 5,12-萘二酮
PNU-159682 95%
PNU-159682 >95%
(8S,10S)-7,8,9,10-Tetrahydro-6,8,11-trihydroxy-8-(2-hydroxyacetyl)-1-methoxy-10-[[(1S,3R,4aS,9S,9aR,10aS)-octahydro-9-methoxy-1-methyl-1H-pyrano[4',3':4,5]oxazolo[2,3-c][1,4]oxazin-3-yl]oxy]-5,12-naphthacenedione
5,12-Naphthacenedione, 7,8,9,10-tetrahydro-6,8,11-trihydroxy-8-(2-hydroxyacetyl)-1-methoxy-10-[[(1S,3R,4aS,9S,9aR,10aS)-octahydro-9-methoxy-1-methyl-1H-pyrano[4',3':4,5]oxazolo[2,3-c][1,4]oxazin-3-yl]oxy]-, (8S,10S)-
物理化學(xué)性質(zhì)
常見問(wèn)題列表
Daunorubicins/Doxorubicins
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Topoisomerase I
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PNU-159682 (0-500 nM; exposed to the compounds for 1 hour and then cultured in compound-free medium for 72 hours) has cytotoxic effects on human tumor cell lines in a sulforhodamine B assay. The IC 70 values are 0.577 nM, 0.39 nM, 0.128 nM, and 0.081 nM, 0.086 nM and 0.075 nM for HT-29, A2780, DU145, EM-2, Jurkat and CEM cells, respectively. It against human tumor cell lines with IC 70 in the ranging 68 nM-578 nM and 181 nM-1717 nM towards MMDX and doxorubicin, respectively. PNU-159682 is more potent than MMAE on NHL cell lines. In a cell viability assay, PNU-159682 is against BJAB.Luc, Granta-519, SuDHL4.Luc, and WSU-DLCL2 with IC 50 values of 0.10 nM, 0.020 nM, 0.055 nM, and 0.1 nM, respectively. While MMAE is against BJAB.Luc, Granta-519, SuDHL4.Luc, and WSU-DLCL2 with IC 50 values of 0.54 nM, 0.25 nM, 1.19 nM and 0.25 nM, respectively.PNU-159682 is thousands of times more cytotoxic than doxorubicin and can be used to develop a new class of ADCs. PNU159682?to?anti-CD22?antibody (anti-CD22-NMS249) exhibits strong anti-tumor effects in vitro . Anti-CD22-NMS249 (PNU159682?to?anti-CD22?antibody) is active in in vitro viability assays of NHL cell lines and is 2 to 20 fold more potent than pinatuzumab vedotin, the ADC anti-CD22-NMS249 is against BJAB.Luc, Granta-519, SuDHL4.Luc, and WSU-DLCL2 with IC 50 values of 0.058 nM, 0.030 nM, 0.0221 nM, and 0.01 nM, respectively.PNU-159682 (100 μM) weakly inhibits topoisomerase II unknotting activity. PNU-159682 shows cytotoxic effect on CAIX-expressing SKRC-52 cells with IC 50 of 25 nM.
Cell Viability Assay
Cell Line: | HT-29, A2780, DU145, EM-2, Jurkat and CEM cells |
Concentration: | 0-500 nM |
Incubation Time: | Exposed to the PNU-159682 for 1 hour and then cultured in compound-free medium for 72 hours |
Result: | Was 2,360- to 790-fold and 6,420- to 2,100-fold more potent than MMDX and doxorubicin, respectively. Exhibited IC 70 values of PNU-159682 are in the subnanomolar range (0.07-0.58 nM) and noticeably lower than that recorded for both MMDX and doxorubicin. |
PNU-159682 (single-dose; i.v.15 μg/kg) is a maximum tolerated dose in murine L1210 leukemia model. PNU-159682 shows an improved antitumor activity in vivo. The antitumor effect of PNU-159682 (increase in life span=29%) is comparable to that afforded by 90 μg/kg MMDX (increase in life=36%).PNU-159682 (i.v. 4 μg/kg; q7dx3; 40 days) has a therapeutic response in MX-1 human mammary carcinoma mice. What’s more, from day 39, four out of seven mice receiving PNU-159682 exhibits complete tumor regression.PNU-159682 is more cytotoxic than doxorubicin and can be used to develop a new class of ADCs. PNU159682?to?anti-CD22?antibody (anti-CD22-NMS249) exhibits strong anti-tumor effects in vivo . ADC dose (anti-CD22-NMS249; 50 μg/m2 conjugated PNU-159682) is well tolerated in mice and results in less than 10% weight loss.In the BJAB.Luc model the efficacy of antiCD22-NMS249 (single dose; 2 mg/kg) is similar to anti-CD22-vc-MMAE. At 2 mg/kg dosage, antiCD22-NMS249 gives complete remission of the tumors (NMS249: 110-134%TGI vs. vc-MMAE: 114-143%TGI). Additionally, a single dose of antiCD22-NMS249 at 2 mg/kg results in tumor stasis for three weeks.
Animal Model: | Four- to six-week-old female CD-1 athymic nude mice with MX-1 tumor fragments |
Dosage: | 4 μg/kg |
Administration: | Intravenous injection; q7dx3; 40 days |
Result: | Exhibited anti-cancer effects in MX-1 human mammary carcinoma xenografts to PNU-159682. |