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1201898-17-0 分子结构
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(2R,3R)-2,3-dihydroxybutanedioic acid methyl (1R,9R,10S,11R,12R,19R)-11-(acetyloxy)-4-[(12S,14R,16R)-16-(1,1-difluoroethyl)-12-(methoxycarbonyl)-1,10-diazatetracyclo[12.3.1.0^{3,11}.0^{4,9}]octadeca-3(11),4,6,8-tetraen-12-yl]-12-ethyl-10-hydroxy-5-methoxy-8-methyl-8,16-diazapentacyclo[10.6.1.0^{1,9}.0^{2,7}.0^{16,19}]nonadeca-2,4,6,13-tetraene-10-carboxylate

ChemBase编号:72901
分子式:C49H60F2N4O14
平均质量:967.0159064
单一同位素质量:966.40740906
SMILES和InChIs

SMILES:
c1(c(cc2c(c1)[C@@]13[C@@H](N2C)[C@@]([C@@H]([C@]2([C@@H]1N(CC=C2)CC3)CC)OC(=O)C)(O)C(=O)OC)OC)[C@@]1(c2c(c3c([nH]2)cccc3)CN2C[C@@H](C[C@H](C1)C2)C(C)(F)F)C(=O)OC.C(=O)(O)[C@@H]([C@H](C(=O)O)O)O
Canonical SMILES:
OC(=O)[C@@H]([C@H](C(=O)O)O)O.COc1cc2N(C)[C@@H]3[C@@]4(c2cc1[C@]1(C[C@@H]2CN(Cc5c1[nH]c1c5cccc1)C[C@@H](C2)C(F)(F)C)C(=O)OC)CCN1[C@H]4[C@@]([C@H]([C@]3(O)C(=O)OC)OC(=O)C)(CC)C=CC1
InChI:
InChI=1S/C45H54F2N4O8.C4H6O6/c1-8-42-14-11-16-51-17-15-43(36(42)51)30-19-31(34(56-5)20-33(30)49(4)37(43)45(55,40(54)58-7)38(42)59-25(2)52)44(39(53)57-6)21-26-18-27(41(3,46)47)23-50(22-26)24-29-28-12-9-10-13-32(28)48-35(29)44;5-1(3(7)8)2(6)4(9)10/h9-14,19-20,26-27,36-38,48,55H,8,15-18,21-24H2,1-7H3;1-2,5-6H,(H,7,8)(H,9,10)/t26-,27-,36+,37-,38-,42-,43-,44+,45+;1-,2-/m11/s1
InChIKey:
TXONSEMUKVZUON-SYVFVGEFSA-N

引用这个纪录

CBID:72901 http://www.chembase.cn/molecule-72901.html

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名称和登记号

名称和登记号

名称 登记号
IUPAC标准名
(2R,3R)-2,3-dihydroxybutanedioic acid methyl (1R,9R,10S,11R,12R,19R)-11-(acetyloxy)-4-[(12S,14R,16R)-16-(1,1-difluoroethyl)-12-(methoxycarbonyl)-1,10-diazatetracyclo[12.3.1.0^{3,11}.0^{4,9}]octadeca-3(11),4,6,8-tetraen-12-yl]-12-ethyl-10-hydroxy-5-methoxy-8-methyl-8,16-diazapentacyclo[10.6.1.0^{1,9}.0^{2,7}.0^{16,19}]nonadeca-2,4,6,13-tetraene-10-carboxylate
IUPAC传统名
L-tartaric acid; vinflunine
别名
Vinflunine Tartrate
CAS号
1201898-17-0
PubChem SID
162037821
PubChem CID
53245637

数据来源

数据来源

所有数据来源 商品来源 非商品来源
数据来源 数据ID 价格
Selleck Chemicals
S2209 external link 加入购物车 请登录
数据来源 数据ID
PubChem 53245637 external link

理论计算性质

理论计算性质

JChem
Acid pKa 10.868424  质子受体
质子供体 LogD (pH = 5.5) -0.8781617 
LogD (pH = 7.4) 2.6256256  Log P 4.6458116 
摩尔折射率 216.5265 cm3 极化性 84.801506 Å3
极化表面积 133.87 Å2 可自由旋转的化学键 13 
里宾斯基五规则 false 

分子性质

分子性质

安全信息 药理学性质 产品相关信息 生物活性(PubChem)
保存条件
-20°C expand 查看数据来源
作用靶点
Microtubule formation expand 查看数据来源
成盐信息
Tartrate expand 查看数据来源

详细说明

详细说明

Selleck Chemicals Selleck Chemicals
Selleck Chemicals -  S2209 external link
Research Area
Description Cancer
Biological Activity
Description Vinflunine is a new vinca alkaloid uniquely fluorinated with the properties of mitotic-arresting and tubulin-interacting activity.
Targets Microtubule
IC50 1.2 μM [1]
In Vitro The major effects of Vinflunine on dynamic instability are a slowing of the microtubule growth rate, an increase in growth duration, and a reduction in shortening duration. The effects of Vinflunine on the readmilling rate is examined by following [3H]GTP incorporation into MAP-rich microtubules, and the IC50 is 0.42 μM. [1] Vinflunine induced mitotic accumulation with IC50 with 18.8 nM, which decreases the centromere dynamicity by 44% and increases the time centromeres spent ina paused state by 63%. [2] Vinflunine ditartrate exhibits microtubule inhibition (purified tubulin and MTP) and cytotoxicity in L1210 cells with IC50 of (0.49 μM and 3.5 μM) and 97 nM, respectively. [3] Vinflunine induces apoptosis in neuroblastoma SK-N-SH cells through a postmitotic G1 arrest and a mitochondrial pathway in a concentration-dependent manner with an IC50 with 50 nM. sup>[4] Treatment of Vinflunine induces a rapid change in endothelial cell shape: cells retracts and assumes a rounded morphology. Mean IC50 values are 9.9 × 10-5 M × 10-5 M for fibronectin and 5.0× 10-5-5-8-4-7 × 10-7 M. [5]
In Vivo Intravenous treatment of mice with Vinflunine, immediately before and 2 day afterMatrigel implantation, results in a dose-dependent inhibition of the bFGF-induced angiogenic response, compared with vehicle-treated animals. Inhibition of haemoglobin content is significant at 1.25, 2.5 and 5 mg/kg, with no effect at 0.63 mg/kg (P > 0.05). An ID50 value (dose which inhibits 50% of bFGF-induced neovascularisation) is calculated as 1 mg/kg. Low doses of Vinflunine reduce the number of experimental liver metastases by human LS174T colon cancer cell. A slight overall decrease in liver metastatic foci is already observed at the very low dose of 0.16 mg/kg Vinflunine, although maximal overall inhibition was reached at the maximal tolerated dose (MTD) of 20 mg/kg. [5]
Clinical Trials Vinflunine is now under the Phase 2 clinical trial to clarify the benefit/risk ration of cytotoxics in CDDP-unfit patients with advanced transitional cell carcinoma.
Features
Combination Therapy
Description Vinflunine combined with Pazopanib is under the Phase 2 clinical trail in urothelial cancer of the bladder.
Protocol
Kinase Assay [1]
Determination of Microtubule Polymer Mass Purified tubulin (17 μM) is polymerized into microtubules in the abence or presence of a range of vnflunine concentrations (35 minutes; 37 °C) in 75 mM PIPES, 1.8 mM MgCl2, 1.0 mM EGTA, and 1.5 mM GTP (pH 6.8) using sea urchin (Strongylocentrotus purpuratus) axonemes as seeds for assembly initiation. After incubation, polymerized microtubules are separated from unpolymerized tubulin by centrifugation (150,000 × g; 1 hour; 35 °C). The supernatant is aspirated, the sedimented microtubules are depolymerized in assembly buffer by incubation on ice (2 hours), and the protein content is determined.
Microtubule Inhibition PC-tubulin (1.8 mg/mL) is polymerized in 100 mM MES, pH 6.9, 10 mM MgSO4, 2 mM EGTA, 1 mM GTP, and 2 M glycerol Experiments are carried out in the presence and absence of test compounds over concentration ranges of 0.1 to 1 μM. Microtubule formation is monitored using a Gilford Response II UV-Vis or a Varian Cary 3E scanning spectrophotometer equipped with a cooling Peltier cell holder. Prior to polymerization, samples are degassed on ice for 30 minutes, and baseline data are collected at 4 °C and 350 nm. The temperature was increased to 37 °C, and solutions are monitored at 350 nm for 45 minutes. Solutions are cooled to 0 °C, and a second baseline is recorded. The change in optical density is plotted vs compound concentration after subtracting the second baseline from the plateau optical density at 45 minutes. This ΔOD corresponds tothe temperature-sensitive reversible polymerization and corrects for irreversible aggregation. The percent inhibition is calculated relative to the control sample. The IC50 concentration (drug concentration causing 50% inhibition of microtubule assembly) is determined from the mean of three independent experiments.
Cell Assay [3]
Cell Lines Leukemic L1210 cell
Concentrations 0-1μM
Incubation Time 48 hours
Methods Effects of Vinflunine on L1210 cell proliferation are determined using a standard growth inhibition assay. Exponentially growing L1210 cells (1.5 × 105 cells/well) in a 24-well plate are exposed to a range of concentrations of test compounds for 48 hours, prior to determining cell numbers using an electronic particle counter based on linear interpolation between data points.
Animal Study [5]
Animal Models LS174T tumor cells are injected into the spleen of BALB/C nude mice.
Formulation Vinflunine is solubilized in a saline solution (0.9% NaCl).
Doses ~20 mg/kg
Administration Administered via i.v. on days 4, 7, 11, 14, 18 and 21 after tumor cell implantation.
References
[1] Ngan VK, et al, Cancer Res, 2000, 60(18), 5045-5051.
[2] Lobert S, et al, Biochemistry, 2000, 39(39), 12053-12062.
[3] Okauneva T, et al, Mol Cancer Ther, 2003, 2(5), 427-436.
[4] Pourroy B, et al, Mol Pharmacol, 2004, 66(3), 580-591.
[5] Kruczynski A, et al, Eur J Cancer, 2006, 42(16), 2821-2832.

参考文献

参考文献

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