For research use only. Not for therapeutic Use.
Nemorubicin (Methoxymorpholinyl doxorubicin) is a Doxorubicin derivative with potent antitumor activity. Nemorubicin is highly cytotoxic to a variety of tumor cell lines presenting a multidrug-resistant phenotype. Nemorubicin not only intercalate into the duplex DNA, but also result in significant ligands for G-quadruplex DNA segments, stabilizing their structure. Nemorubicin requirs an intact nucleotide excision repair (NER) system to exert its activity[1][2][3][4].
Nemorubicin has antitumor activity, with IC70s of 578 nM, 468 nM, 193 nM, 191 nM, 68 nM, and 131 ± 9 nM for HT-29, A2780, DU145, EM-2, Jurkat and CEM cell lines, respectively[1].
Nemorubicin is CYP3A-activated anticancer prodrug, which can produce a more cytotoxic metabolite, PNU-159682[1][2].
Nemorubicin acts through nucleotide excision repair (NER) system to exert its activity. Nemorubicin (0-0.3 μM) is more active in the L1210/DDP cells with intact NER than in the XPG-deficient L1210/0 cells. Cells resistant to nemorubicin show increased sensitivity to UV damage[3].
Nemorubicin is cytotoxic to 9L/3A4 cells, with an IC50 of 0.2 nM, 120-fold lower than that of P450-deficient 9L cells (IC50, 23.9 nM). Nemorubicin also potently inhibits Adeno-3A4 infected U251 cells with IC50 of 1.4 nM. P450 reductase overexpression enhances cytotoxicity of Nemorubicin[4].
Nemorubicin is converted to PNU-159682 by human liver cytochrome P450 (CYP) 3A4 in rat, mouse, and dog liver microsomes[2].
Nemorubicin (60 µg/kg) induces sifnificant tumor growth delay in scid mice bearing 9L/3A4 tumors, but shows no obvious effect on the tumor growth delay of 9L tumors in mice by i.v. or intratumoral injection (i.t.). Nemorubicin (40 µg/kg, i.p.) exhibits no antitumor activity and no host toxicity in mice bearing 9L/3A4 tumors[4].
| Catalog Number | I000374 |
| CAS Number | 108852-90-0 |
| Synonyms | (7S,9S)-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-7-[(2R,4S,5S,6S)-5-hydroxy-4-[(2S)-2-methoxymorpholin-4-yl]-6-methyloxan-2-yl]oxy-4-methoxy-8,10-dihydro-7H-tetracene-5,12-dione |
| Molecular Formula | C32H37NO13 |
| Purity | ≥95% |
| InChI | InChI=1S/C32H37NO13/c1-14-27(36)17(33-7-8-44-22(12-33)43-3)9-21(45-14)46-19-11-32(41,20(35)13-34)10-16-24(19)31(40)26-25(29(16)38)28(37)15-5-4-6-18(42-2)23(15)30(26)39/h4-6,14,17,19,21-22,27,34,36,38,40-41H,7-13H2,1-3H3/t14-,17-,19-,21-,22-,27+,32-/m0/s1 |
| InChIKey | CTMCWCONSULRHO-UHQPFXKFSA-N |
| SMILES | CC1C(C(CC(O1)OC2CC(CC3=C2C(=C4C(=C3O)C(=O)C5=C(C4=O)C(=CC=C5)OC)O)(C(=O)CO)O)N6CCOC(C6)OC)O |
| Reference | [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]. Quintieri L, et al. In vitro hepatic conversion of the anticancer agent nemorubicin to its active metabolite PNU-159682 in mice, rats and dogs: a comparison with human liver microsomes. Biochem Pharmacol. 2008 Sep 15;76(6):784-95. [3]. Sabatino MA, et al. Down-regulation of the nucleotide excision repair gene XPG as a new mechanism of drug resistance in human and murine cancer cells. Mol Cancer. 2010 Sep 24;9:259. [4]. Lu H, et al. Potentiation of methoxymorpholinyl doxorubicin antitumor activity by P450 3A4 gene transfer. Cancer Gene Ther. 2009 May;16(5):393-404. |
