Nemorubicin是一种具有有效抗肿瘤活性的 Doxor

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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

643.64

Solid

C₃₂H₃₇NO₁₃

108852-90-0

奈莫柔比星

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• 1.

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• [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. [Content Brief]

  [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. [Content Brief]

  [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. [Content Brief]

  [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. [Content Brief]