O-6-苄基鸟嘌呤

O-6-苄基鸟嘌呤用途

O6-Benzylguanine 是鸟嘌呤类似物,是 DNA 修复酶 O6 烷基鸟嘌呤DNA烷基转移酶 (MGMT/AGT) 抑制剂。O6-Benzylguanine 作为 AGT 底物,将其苄基转移到 AGT 半胱氨酸残基上,从而不可逆地灭活 AGT 并阻止 DNA 修复。O6-Benzylguanine 诱导肿瘤细胞凋亡,具有抗肿瘤活性。

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O-6-苄基鸟嘌呤名称

[ CAS 号 ]:
19916-73-5

[ 中文名 ]:
O-6-苄基鸟嘌呤

[ 英文名 ]:
O6-Benzylguanine

[中文别名 ]:

[英文别名 ]:

O(6)-Benzylguanine
7H-purin-2-amine, 6-(phenylmethoxy)-
O6-Benzylguanine
2-amino-6-(phenylmethoxy)-9H-purine
O(6)-bGua
2-Amino-6-benzyloxy-9H-purine
O-6-Benzylguanine
6-Benzyloxy guanine
6-(Benzyloxy)-3H-purin-2-amine
2-Amino-6-(benzyloxy)purine

O-6-苄基鸟嘌呤生物活性

[ 描述 ]:

[ 相关类别 ]:

信号通路 >> 细胞凋亡 >> 细胞凋亡

研究领域 >> 癌症

信号通路 >> 细胞周期/DNA损伤 >> DNA/RNA合成

[体外研究]

L3.6pl细胞对O6苄基鸟嘌呤(24-72小时)相对敏感,呈剂量和时间依赖性。IC50为50μg(在48小时内)[2]。O6-苄基鸟嘌呤(50μg；48小时)调节p53下游靶蛋白表达,诱导细胞凋亡,降低细胞增殖[2]。O6苄基鸟嘌呤(50μg；48小时)显著降低L3.6pl中MGMT的转录活性[2]。Western Blot分析[2]细胞株：L3.6pl,PANC1细胞浓度：50μg孵育时间：48h结果：O6甲基鸟嘌呤DNA甲基转移酶(MGMT)、细胞周期蛋白B1、细胞周期蛋白B2、细胞周期蛋白A、p53、ki-67表达降低,p21表达升高。细胞C和caspase 9水平升高,而PARP1蛋白水平降低。RT-PCR[2]细胞株：L3.6pl细胞浓度：50μg孵育时间：48h结果：L3.6pl细胞MGMT转录活性降低。

[体内研究]

O6苄基鸟嘌呤(100μg；i.p.；每日35天)抑制胰腺癌细胞生长,增加胰腺细胞对吉西他滨(100 mg/kg)的敏感性[2]。O6苄基鸟嘌呤抑制胰腺癌细胞增殖并诱导肿瘤细胞凋亡[2]。动物模型：雄性裸鼠(NCI-nu)(含人胰腺癌L3.6pl细胞)[2]剂量：100μg给药：i.p；每日35天结果：肿瘤体积和重量中位数显著降低。

[参考文献]

[1]. Rabik CA, Njoku MC, Dolan ME. Inactivation of O6-alkylguanine DNA alkyltransferase as a means to enhance chemotherapy. Cancer Treat Rev. 2006;32(4):261‐276.

[2]. Konduri, Santhi D et al. Blockade of MGMT expression by O6 benzyl guanine leads to inhibition of pancreatic cancer growth and induction of apoptosis. Clinical cancer research : an official journal of the American Association for Cancer Research vol. 15,19 (2009): 6087-95.

O-6-苄基鸟嘌呤物理化学性质

[ 密度 ]:
1.4±0.1 g/cm3

[ 沸点 ]:
621.4±63.0 °C at 760 mmHg

[ 熔点 ]:
193(dec.)

[ 分子式 ]:
C₁₂H₁₁N₅O

[ 分子量 ]:
241.249

[ 闪点 ]:
329.6±33.7 °C

[ 精确质量 ]:
241.096359

[ PSA ]:
89.71000

[ LogP ]:
1.95

[ 外观性状 ]:
淡黄色固体

[ 蒸汽压 ]:
0.0±1.8 mmHg at 25°C

[ 折射率 ]:
1.743

[ 储存条件 ]:
-20°C Freezer

[ 水溶解性 ]:
methanol: 20 mg/mL

O-6-苄基鸟嘌呤MSDS

详细MSDS(安全技术说明书)

O-6-苄基鸟嘌呤安全信息

[ 符号 ]:

GHS07

[ 信号词 ]:
Warning

[ 危害声明 ]:
H315-H319-H335

[ 警示性声明 ]:
P261-P305 + P351 + P338

[ 个人防护装备 ]:
dust mask type N95 (US);Eyeshields;Gloves

[ 危害码 (欧洲) ]:
Xi:Irritant;

[ 风险声明 (欧洲) ]:
R36/37/38

[ 安全声明 (欧洲) ]:
S26-S36

[ 危险品运输编码 ]:
NONH for all modes of transport

[ WGK德国 ]:
3

[ 海关编码 ]:
2933990090

O-6-苄基鸟嘌呤上下游产品

O-6-苄基鸟嘌呤上游产品

O-6-苄基鸟嘌呤下游产品

O-6-苄基鸟嘌呤海关

[ 海关编码 ]: 2933990090

[ 中文概述 ]:
2933990090. 其他仅含氮杂原子的杂环化合物. 增值税率:17.0%. 退税率:13.0%. 监管条件:无. 最惠国关税:6.5%. 普通关税:20.0%

[ 申报要素 ]: 品名, 成分含量, 用途, 乌洛托品请注明外观, 6－己内酰胺请注明外观, 签约日期

[ Summary ]:
2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

O-6-苄基鸟嘌呤文献

Differential expression of miR200a-3p and miR21 in grade II-III and grade IV gliomas: evidence that miR200a-3p is regulated by O⁶-methylguanine methyltransferase and promotes temozolomide responsiveness.

Cancer Biol. Ther. 15(7) , 938-50, (2014)

Glioblastoma multiforme (GBM) is the most common primary brain tumor and is among the deadliest of human cancers. Dysregulation of microRNAs (miRNAs) expression is an important step in tumor progressi...

Formation and repair of pyridyloxobutyl DNA adducts and their relationship to tumor yield in A/J mice.

Chem. Res. Toxicol. 25(10) , 2167-78, (2012)

The nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a known human carcinogen. It generates methyl and pyridyloxobutyl DNA adducts. The role of the methyl DNA adducts has been well-...

Evaluation of novel imidazotetrazine analogues designed to overcome temozolomide resistance and glioblastoma regrowth.

Mol. Cancer Ther. 14(1) , 111-9, (2015)

The cellular responses to two new temozolomide (TMZ) analogues, DP68 and DP86, acting against glioblastoma multiforme (GBM) cell lines and primary culture models are reported. Dose-response analysis o...

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