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苦鬼臼毒素

苦鬼臼毒素用途

Picropodophyllin (AXL1717) 是选择性的胰岛素样生长因子-1受体 (IGF-1R)抑制剂,IC50 为1 nM。

苦鬼臼毒素名称

[ CAS 号 ]:
477-47-4

[ 中文名 ]:
苦鬼臼毒素

[ 英文名 ]:
Picropodophyllotoxin

[中文别名 ]:

[英文别名 ]:

Picropodophyllinic Acid Lactone
Picropodophyllin (8CI)
Picropodophyllotoxin
Picropodophyllin
PPP
IGF-1R Inhibitor
AXL1717

苦鬼臼毒素生物活性

[ 描述 ]:

Picropodophyllin (AXL1717) 是选择性的胰岛素样生长因子-1受体 (IGF-1R)抑制剂,IC50 为1 nM。

[ 相关类别 ]:

信号通路 >> 蛋白酪氨酸激酶 >> IGF-1R

研究领域 >> 癌症

[ 靶点 ]

IC50: 1 nM (IGF-1R)

[体外研究]

鬼臼苦素(AXL1717)(0.5,2.5,10μM)有效抑制完整细胞中IGF-1刺激的IGF-1R,Akt(Ser 473)和Erk1/2磷酸化。鬼臼苦素(AXL1717)也抑制细胞生长,并诱导培养的IGF-1R阳性肿瘤细胞凋亡[1]。鬼臼苦素(AXL1717)通过进一步降低细胞活力和增强细胞凋亡,协同增敏HMCL,原代人MM和鼠5T33MM细胞对ABT-737和ABT-199的作用[3]。鬼臼苦素和索拉非尼协同抑制肝细胞癌细胞的增殖和运动[4]。

[体内研究]

鬼臼苦素(AXL1717)(20mg/kg/12h,ip)在用人ES-1,BE和PC3异种移植的SCID小鼠中引起完全肿瘤消退[1]。鬼臼苦素(AXL1717)显示出有效的抗肿瘤活性,可提高5T33MM小鼠模型的存活率[2]。

[动物实验]

使用4至5周龄的无病原体SCID小鼠并将其容纳在无菌设施中的塑料隔离器内。 ES-1，BE和PC3细胞（均被证实表达IGF-1R）或Rv-src（IGF-1R阴性）和P12（过表达IGF-1和IGF-1R）以107细胞/小鼠皮下注射在0.2mL体积的无菌盐水溶液中。免疫活性Balb-c小鼠每只小鼠在0.15mL体积的无菌盐水溶液中注射107JC鼠乳腺癌细胞。用鬼臼苦素（AXL1717）（20mg / kg / 12h）进行的实验处理通过每天腹膜内注射10μL体积的DMSO：植物油，10：1（v / v）中的化合物来进行。对照小鼠仅用载体处理。每组治疗三只动物。使用游标卡尺每隔一天测量肿瘤生长，并计算肿瘤体积。仔细观察小鼠是否存在副作用，并在实验结束时将其处死以进行病变的组织学分析。对鬼臼苦素（AXL1717）处理（系统和局部）无肿瘤小鼠的单独实验，包括各种器官的组织学分析，证实了先前观察到鬼臼苦素（AXL1717）似乎是无毒的。

[参考文献]

[1]. Girnita A, et al. Cyclolignans as inhibitors of the insulin-like growth factor-1 receptor and malignant cell growth. Cancer Res. 2004 Jan 1;64(1):236-42.

[2]. Menu E, et al. Inhibiting the IGF-1 receptor tyrosine kinase with the cyclolignan PPP: an in vitro and in vivo study in the 5T33MM mouse model. Blood. 2006 Jan 15;107(2):655-60. Epub 2005 Jul 26.

[3]. Bieghs L, et al. The IGF-1 receptor inhibitor picropodophyllin potentiates the anti-myeloma activity of a BH3-mimetic. Oncotarget. 2014 Nov 30;5(22):11193-208.

[4]. Tomizawa M, et al. Picropodophyllin and sorafenib synergistically suppress the proliferation and motility of hepatocellular carcinoma cells. Oncol Lett. 2014 Nov;8(5):2023-2026. Epub 2014 Aug 27.

[5]. Stromberg T, et al. IGF-1 receptor tyrosine kinase inhibition by the cyclolignan PPP induces G2/M-phase accumulation and apoptosis in multiple myeloma cells. Blood. 2006 Jan 15;107(2):669-78. Epub 2005 Sep 15.

[6]. Kong YL, et al. Insulin deficiency induces rat renal mesangial cell dysfunction via activation of IGF-1/IGF-1R pathway. Acta Pharmacol Sin. 2016 Feb;37(2):217-27.

[相关活性小分子]

苦鬼臼毒素物理化学性质

[ 密度 ]:
1.4±0.1 g/cm3

[ 沸点 ]:
597.9±50.0 °C at 760 mmHg

[ 熔点 ]:
225-227ºC

[ 分子式 ]:
C₂₂H₂₂O₈

[ 分子量 ]:
414.405

[ 闪点 ]:
210.2±23.6 °C

[ 精确质量 ]:
414.131470

[ PSA ]:
92.68000

[ LogP ]:
1.60

[ 外观性状 ]:
白色粉末

[ 蒸汽压 ]:
0.0±1.8 mmHg at 25°C

[ 折射率 ]:
1.606

[ 储存条件 ]:
2-8°C

苦鬼臼毒素MSDS

详细MSDS(安全技术说明书)

苦鬼臼毒素毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: LV2510000

CAS REGISTRY NUMBER :: 477-47-4

BEILSTEIN REFERENCE NO. :: 0099161

LAST UPDATED :: 199801

DATA ITEMS CITED :: 2

MOLECULAR FORMULA :: C22-H22-O8

MOLECULAR WEIGHT :: 414.44

WISWESSER LINE NOTATION :: T E5 C665 FVO NO PO OHTT&&J DR CO1 DO1 EO1& JQ

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 280 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - tremor Lungs, Thorax, or Respiration - respiratory stimulation

REFERENCE :: PSEBAA Proceedings of the Society for Experimental Biology and Medicine. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1903/04- Volume(issue)/page/year: 77,269,1951 *** U.S. STANDARDS AND REGULATIONS *** MSHA STANDARD-air:TWA 0.1 mg/m3 DTLVS* The Threshold Limit Values (TLVs) and Biological Exposure Indices (BEIs) booklet issues by American Conference of Governmental Industrial Hygienists (ACGIH), Cincinnati, OH, 1996 Volume(issue)/page/year: 3,212,1971

苦鬼臼毒素安全信息

[ 符号 ]:

GHS06

[ 信号词 ]:
Danger

[ 危害声明 ]:
H301-H312-H315-H319-H335

[ 警示性声明 ]:
P261-P280-P301 + P310-P305 + P351 + P338

[ 个人防护装备 ]:
Eyeshields;Faceshields;Gloves;type P2 (EN 143) respirator cartridges

[ 危害码 (欧洲) ]:
Xi,T

[ 风险声明 (欧洲) ]:
36/37/38-68-25-21

[ 安全声明 (欧洲) ]:
26-36-45-36/37

[ 危险品运输编码 ]:
UN 3462 6.1/PG 2

[ WGK德国 ]:
3.0

[ RTECS号 ]:
LV2510000

[ 危险类别 ]:
6.1

苦鬼臼毒素合成路线

详细合成路线

苦鬼臼毒素上下游产品

苦鬼臼毒素上游产品

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苦鬼臼毒素文献

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Am. J. Physiol. Renal Physiol. 308(4) , F298-308, (2015)

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