奈莫柔比星

中文名称:

奈莫柔比星

中文同义词:

柰莫柔比星;奈莫柔比星;莫柔比星

英文名称:

Nemorubicin

英文同义词:

Nemorubicin;5,12-Naphthacenedione, 7,8,9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-10-2,3,6-trideoxy-3-(2S)-2-methoxy-4-morpholinyl-.alpha.-L-lyxo-hexopyranosyloxy-, (8S,10S)-;methoxy-morpholynil-doxorubicin;NeMorubincine;PNU152243A; PNU-152243A; PNU 152243A; NEMORUBICIN; METHOXYMORPHOLINYL-DOXORUBICIN;(1S,3S)-3-Glycoloyl-1,2,3,4,6,11-hexahydro-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-1-naphthacenyl 2,3,6-trideoxy-3-[(S)-2-methoxymorpholino]-alpha-L-lyxo-hexopyranoside;DMM Dox;FCE 23762

CAS号:

108852-90-0

分子式:

C32H37NO13

分子量:

643.64

EINECS号:

相关类别:

医药原料药;原料药【仅供科研】;科研原药系列;原料药;≧99%

Mol文件:

108852-90-0.mol

沸点 

852.2±65.0 °C(Predicted)

密度 

1.55±0.1 g/cm3(Predicted)

酸度系数(pKa)

7.35±0.60(Predicted)

CAS 数据库

108852-90-0

生物活性

Nemorubicin (Methoxymorpholinyl doxorubicin) 是一种具有有效抗肿瘤活性的 Doxorubicin 衍生物。Nemorubicin 对多药耐药表型的多种肿瘤细胞系具有细胞毒性。Nemorubicin 需要完整的核苷酸切除修复系统才能发挥其活性。

体外研究

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. Nemorubicin is CYP3A-activated anticancer prodrug, which can produce a more cytotoxic metabolite, PNU-159682. 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. 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.

体内研究

Nemorubicin is converted to PNU-159682 by human liver cytochrome P450 (CYP) 3A4 in rat, mouse, and dog liver microsomes. 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.