西奈芬净
中文名称:
西奈芬净
中文同义词:
西奈芬净;西奈芬近;西奈芬净/D-GLYCERO-A-L-TALO-DECOFURANURONIC ACID,6,9-DIAMINO-1-(6-AMINO-9H-PURIN-9-YL)-1,5,6,7,8,9-HEXADEOXY-
英文名称:
SINEFUNGIN
英文同义词:
6,7,8,9-hexadeoxy-yl)-5;6,9-diamino-1-(6-amino-9h-purin-9-d-glycero-alpha-l-talo-decofuranuronicaci;6,9-diamino-1-(6-amino-9h-purin-9-yl)-1,5,6,7,8,9-hexadeoxydecofuranuronica;compound57926;rp32232;SF;SINEFUNGIN;5-DEOXY-5-(1,4-DIAMINO-4-CARBOXYBUTYL)ADENOSINE
CAS号:
58944-73-3
分子式:
C15H23N7O5
分子量:
381.39
EINECS号:
637-385-5
相关类别:
医药原料药;微生物代谢物;化工原料
Mol文件:
58944-73-3.mol
比旋光度
D25 -2.61° (c = 5 in water); D23 +12 ±2° (c = 0.227 in water)
沸点
783.2±70.0 °C(Predicted)
密度
1.91±0.1 g/cm3(Predicted)
储存条件
2-8°C
溶解度
H2O: soluble
形态
powder
酸度系数(pKa)
pKa (66% DMF): 2.9, 3.9, 8.9, 10.2(at 25℃)
颜色
white to yellow
腺苷衍生物
西奈芬净（9，sinefungin）是一种腺苷衍生物，属于泛甲基转移酶抑制剂，最初作为一种潜在的抗真菌药物从灰质链霉菌中分离出来。Hercik 等报道了西奈芬净与ZIKV甲基转移酶所形成配合物的晶体结构。SAM 为MTase 的天然底物，西奈芬净是其竞争性抑制剂。 西奈芬净与GTP 和GDP 类似物相结合，可能增强这些类似物对酶的亲和力，从而得到更好的选择性和对ZIKV 复制更强的抑制作用。然而，西奈芬净作为抗寄生虫剂在犬和山羊上进行实验时，被发现具有毒性，阻碍了其临床应用。
生物活性
Sinefungin是病毒粒子mRNA (鸟嘌呤-7-)-甲基转移酶、 mRNA (核苷-2-)-甲基转移酶和病毒增殖的有效抑制剂。Sinefungin 是一种 SET7/9 抑制剂，通过抑制H3K4甲基化来改善肾纤维化。
体外研究
Sinefungin (0.5 or 1.0 μg/mL, 60 minutes) ameliorates the TGF-β1-induced increase of α-SMA and inhibits the upregulation of histone H3K4 monomethylation in renal epithelial cells and renal fibroblast cells.
Western Blot Analysis
Cell Line: Renal epithelial cells.
Concentration: 0.5 or 1.0 μg/mL.
Incubation Time: Pretreatment 60 minutes before TGF-β1 (10 ng/mL).
Result: Significantly reduced TGF-β1-inducedα-SMA protein expression and inhibited H3K4me1 in a dose-dependent manner in both NRK-52E and NRK-49F cells.
Cell Line:
Renal epithelial cells.
Concentration:
0.5 or 1.0 μg/mL.
Incubation Time:
Pretreatment 60 minutes before TGF-β1 (10 ng/mL).
Result:
Significantly reduced TGF-β1-inducedα-SMA protein expression and inhibited H3K4me1 in a dose-dependent manner in both NRK-52E and NRK-49F cells.
体内研究
Sinefungin (10 mg/kg, per day immediately after UUO) ameliorates renal fibrosis in obstructive nephropathy.
Animal Model: Male C57BL/6J mice (8 weeks of age).
Dosage: 10 mg/kg
Administration: Administered intraperitoneally per day immediately after UUO (prepared as a suspension in distilled water and 0.9% NaCl solution).
Result: Inhibited α-SMA protein expression.
Ameliorated those (α-SMA, FSP-1, collagen 1, collagen 3) both at 3 and 7 days after UUO.
Animal Model:
Male C57BL/6J mice (8 weeks of age).
Dosage:
10 mg/kg
Administration:
Administered intraperitoneally per day immediately after UUO (prepared as a suspension in distilled water and 0.9% NaCl solution).
Result:
Inhibited α-SMA protein expression.
Ameliorated those (α-SMA, FSP-1, collagen 1, collagen 3) both at 3 and 7 days after UUO.
危险品标志
Xn
危险类别码
22
安全说明
36
WGK Germany
3
RTECS号
HE3140000
海关编码
29419090
毒性
LD50 s.c. in mice: 185 mg/kg (Hamill, Hoehn, J. Antibiot.)
