[CAS NO. 108852-90-0] Nemorubicin
PRODUCTS SPECIFICATIONS [108852-90-0]
DESCRIPTION [108852-90-0]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 643.64 |
| Molecular Formula | C32H37NO13 |
| SMILES | COC1=C2C(C(C3=C(O)C(C[C@](C(CO)=O)(O)C[C@]4([H])O[C@H]5C[C@H](N6CCO[C@H](OC)C6)[C@H](O)[C@H](C)O5)=C4C(O)=C3C2=O)=O)=CC=C1 |
Summary
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] .
In Vitro
Nemorubicin has antitumor activity, with IC
70
s 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 IC
50
of 0.2 nM, 120-fold lower than that of P450-deficient 9L cells (IC
50
, 23.9 nM). Nemorubicin also potently inhibits Adeno-3A4 infected U251 cells with IC
50
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.
In Vivo
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.
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 65 mg/mL ( 100.99 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.5537 mL | 7.7683 mL | 15.5366 mL |
| 5 mM | 0.3107 mL | 1.5537 mL | 3.1073 mL |
| 10 mM | 0.1554 mL | 0.7768 mL | 1.5537 mL |
-
1.
References
- [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.
Synonyms