丙脒腙

丙脒腙用途

Mitoguazone (Methylglyoxal-bis(guanylhydrazone)) 是一种具有有效抗肿瘤活性的合成多羰基衍生物。Mitoguazone 是一种可透过血脑屏障的竞争性的 S-腺苷-蛋氨酸脱羧酶 (S-adenosyl-methionine decarboxylase) 抑制剂,可破坏多胺的生物合成。Mitoguazone 诱导细胞凋亡 (apoptosis),可抑制 HIV DNA 整合到单核细胞和巨噬细胞中的细胞 DNA 中。Mitoguazone 具可用于急性白血病,霍奇金淋巴瘤和非霍奇金淋巴瘤的研究。

丙脒腙名称

[ CAS 号 ]:
459-86-9

[ 中文名 ]:
米托胍腙

[ 英文名 ]:
Mitoguazone

[中文别名 ]:

[英文别名 ]:

Mitoguazone
Me-GAG
Pyruvaldehyde bis(amidinohydrazone)
methylglyoxal bis-(guanylhydrazone)
1,1'-((methylethanediylidene)dinitrilo)diguanidine
methyl-g
MGBG
methyl-gag
1,1'-((methylethanediylidene)dinitrilo)di-guanidin

丙脒腙生物活性

[ 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 >> 抗感染 >> HIV

研究领域 >> 感染

[体外研究]

当浓度为1.0μg/g时,μg/g的瓜氨酸抑制线粒体合成。在3株Burkitt淋巴瘤细胞系(Raji、Ramos和Daudi)和1株前列腺癌细胞系(mpc3)中,检测了米托瓜酮通过抑制多胺途径诱导细胞凋亡的能力。米托瓜酮诱导所有不同的人乳腺癌细胞系凋亡,呈浓度和时间依赖性,并在人乳腺癌MCF7细胞系中引发p53非依赖性程序性细胞死亡[2]。

[体内研究]

研究了不同阶段白血病P388对抗肿瘤药物米托瓜酮在小鼠体内药动学的影响。与所研究的肿瘤分期无关,米托瓜酮的总清除率略有降低,反映出白血病动物血清中AUC的适度升高。此外,与早期白血病相比,在肿瘤晚期,肾脏、肝脏、脾脏和血清中的药物水平与无瘤对照组相比有一定程度的升高[5]。

[参考文献]

[1]. J Rizzo, et al. Pharmacokinetic Profile of Mitoguazone (MGBG) in Patients With AIDS Related non-Hodgkin's Lymphoma. Invest New Drugs. 1996;14(2):227-34.

[2]. K Davidson, et al. Mitoguazone Induces Apoptosis via a p53-independent Mechanism. Anticancer Drugs. 1998 Aug;9(7):635-40.

[3]. Xia Jin, et al. Inhibition of HIV Expression and Integration in Macrophages by Methylglyoxal-Bis-Guanylhydrazone. J Virol. 2015 Nov;89(22):11176-89.

[4]. A M Levine, et al. Mitoguazone Therapy in Patients With Refractory or Relapsed AIDS-related Lymphoma: Results From a Multicenter Phase II Trial. J Clin Oncol. 1997 Mar;15(3):1094-103.

[5]. R Amlacher, et al. Influence of Leukemia P388 on the Pharmacokinetics of Mitoguazone in B6D2F1 Mice. Pharmazie. 1990 May;45(5):364-6.

丙脒腙物理化学性质

[ 密度 ]:
1.55g/cm3

[ 沸点 ]:
436.6ºC at 760mmHg

[ 分子式 ]:
C₅H₁₂N₈

[ 分子量 ]:
184.20200

[ 闪点 ]:
217.8ºC

[ 精确质量 ]:
184.11800

[ PSA ]:
148.52000

[ LogP ]:
0.69610

[ 蒸汽压 ]:
7.99E-08mmHg at 25°C

[ 折射率 ]:
1.692

[ 储存条件 ]:
室温

丙脒腙毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: MF3860000

CHEMICAL NAME :: Guanidine, 1,1'-((methylethanediylidene)dinitrilo)di-

CAS REGISTRY NUMBER :: 459-86-9

LAST UPDATED :: 199612

DATA ITEMS CITED :: 4

MOLECULAR FORMULA :: C5-H12-N8

MOLECULAR WEIGHT :: 184.25

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >150 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1260 mg/kg

SEX/DURATION :: male 7 day(s) pre-mating female 7 day(s) pre-mating - 7 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - female fertility index (e.g. # females pregnant per # sperm positive females; # females pregnant per # females mated)

MUTATION DATA

TYPE OF TEST :: DNA inhibition

TEST SYSTEM :: Mammal - cattle Lymphocyte

DOSE/DURATION :: 8 umol/L

REFERENCE :: CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut Sts., Philadelphia, PA 19106) V.1- 1941- Volume(issue)/page/year: 37,3169,1977

丙脒腙