S84294 |
PNU-159682 |
| 源叶(MedMol) | 95% |
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- 产品描述： PNU-159682, a metabolite of the anthracycline Nemorubicin, is a highly potent DNA topoisomerase II inhibitor with excellent cytotoxicity. PNU-159682 acts as a more potent and tolerated?ADC cytotoxin than Doxorubicin for ADC synthesis. PNU-159682 can be used in EDV-nanocell technology to overcome agent resistance
- 靶点： Daunorubicins/Doxorubicins;Topoisomerase I
- 体外研究： 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 IC70 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 IC70 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 IC50 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 IC50 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 IC50 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 c
- 体内研究： 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.
- 参考文献：
1. Quintieri L, et al. Formation and antitumor activity of PNU-159682, a major metabolite of nemorubicin in human liver microsomes. Clin Cancer Res. 2005 Feb 15;11(4):1608-17. 2. Cazzamalli S, et al. Acetazolamide Serves as Selective Delivery Vehicle for Dipeptide-Linked Drugs to Renal Cell Carcinoma. Mol Cancer Ther. 2016 Dec;15(12):2926-2935. 3. Pengxuan Zhao, et al. Recent advances of antibody drug conjugates for clinical applications. Acta Pharm Sin B. 2020 Sep;10(9):1589-1600. 4. Joanne Lundy, Interim data: Phase I/IIa study of EGFR-targeted EDV nanocells carrying cytotoxic drug PNU-159682 (E-EDV-D682) with immunomodulatory adjuvant EDVs carrying α-galactosyl ceramide (EDV-GC) in patients with recurrent, metastatic pancreatic cancer. GASTROINTESTINAL CANCER—GASTROESOPHAGEAL, PANCREATIC, AND HEPATOBILIARY
- 溶解性： Soluble in DMSO
- 保存条件： -20℃
- 配置溶液浓度参考：
1mg 5mg 10mg 1 mM 1.559 ml 7.793 ml 15.586 ml 5 mM 0.312 ml 1.559 ml 3.117 ml 10 mM 0.156 ml 0.779 ml 1.559 ml 50 mM 0.031 ml 0.156 ml 0.312 ml
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