您当前所在的位置:首页 > 产品中心 > 产品详细信息
4449-51-8 分子结构
点击图片或这里关闭

(1'S,2R,2'R,3R,3aS,5'S,6S,7aR,10'S,11'S)-2',3,6,15'-tetramethyl-3a,4,5,6,7,7a-hexahydro-3H-spiro[furo[3,2-b]pyridine-2,14'-tetracyclo[8.7.0.02,7.011,16]heptadecane]-7',15'-dien-5'-ol

ChemBase编号:72542
分子式:C27H41NO2
平均质量:411.61994
单一同位素质量:411.31372956
SMILES和InChIs

SMILES:
C1[C@@H](CC2=CC[C@@H]3[C@@H]([C@]2(C1)C)CC1=C([C@]2(CC[C@@H]31)O[C@H]1[C@H]([C@H]2C)NC[C@H](C1)C)C)O
Canonical SMILES:
O[C@H]1CC[C@]2(C(=CC[C@@H]3[C@@H]2CC2=C(C)[C@]4(CC[C@@H]32)O[C@H]2[C@H]([C@H]4C)NC[C@H](C2)C)C1)C
InChI:
InChI=1S/C27H41NO2/c1-15-11-24-25(28-14-15)17(3)27(30-24)10-8-20-21-6-5-18-12-19(29)7-9-26(18,4)23(21)13-22(20)16(27)2/h5,15,17,19-21,23-25,28-29H,6-14H2,1-4H3/t15-,17+,19-,20-,21-,23-,24+,25-,26-,27-/m0/s1
InChIKey:
QASFUMOKHFSJGL-LAFRSMQTSA-N

引用这个纪录

CBID:72542 http://www.chembase.cn/molecule-72542.html

Collapse All Expand All

名称和登记号

名称和登记号

名称 登记号
IUPAC标准名
(1'S,2R,2'R,3R,3aS,5'S,6S,7aR,10'S,11'S)-2',3,6,15'-tetramethyl-3a,4,5,6,7,7a-hexahydro-3H-spiro[furo[3,2-b]pyridine-2,14'-tetracyclo[8.7.0.02,7.011,16]heptadecane]-7',15'-dien-5'-ol
(3S,3'R,3'aS,6'S,6aS,6bS,7'aR,9R,11aS,11bR)-3',6',10,11b-tetramethyl-1,2,3,3'a,4,4',5',6,6',6a,6b,7,7',7'a,8,11,11a,11b-octadecahydro-3'H-spiro[cyclohexa[a]fluorene-9,2'-furo[3,2-b]pyridine]-3-ol
IUPAC传统名
cyclopamine
(3S,3'R,3'aS,6'S,6aS,6bS,7'aR,9R,11aS,11bR)-3',6',10,11b-tetramethyl-2,3,3'a,4,4',5',6,6',6a,6b,7,7',7'a,8,11,11a-hexadecahydro-1H,3'H-spiro[cyclohexa[a]fluorene-9,2'-furo[3,2-b]pyridine]-3-ol
别名
? 11-Deoxojervine
? (2′R,3S,3′R,3′aS,6′S,6aS,6bS,7′aR,11aS,11bR)-1,2,3,3′a,4,4′,5′,6,6′,6a,6b,7,7′,7'a,8,11,11a,11b-octadecahydro-3′,6′,10,11b-tetramethyl-spiro[9H-benzo[a]fluorene-9,2′(3′H)-furo[3,2-b]pyridin]-3-ol
(2'R,3S,3'R,3'aS,6'S,6aS,6bS,7'aR,11aS,11bR)-1,2,3,3'a,4,4',5',6,6',6a,6b,7,7',7'a,8,11,11a,11b-Octadecahydro-3',6',10,11b-tetramethylspiro[9H-benzo[a]fluorene-9,2'(3'H)-furo[3,2-b]pyridin]-3-ol Tartrate
11-Deoxojervine Tartrate
(3β,23β)-17,23-Epoxy-veratraman-3-ol Tartrate
11-Deoxyjervine Tartrate
Cyclopamine Tartrate
(2'R,3S,3'R,3'aS,6'S,6aS,6bS,7'aR,11aS,11bR)-1,2,3,3'a,4,4',5',6,6',6a,6b,7,7',7'a,8,11,11a,11b-Octadecahydro-3',6',10,11b-tetramethylspiro[9H-benzo[a]fluorene-9,2'(3'H)-furo[3,2-b]pyridin]-3-ol
(3β,23β)-17,23-Epoxyveratraman-3-ol
11-Deoxyjervine
11-deoxojervine
Cyclopamine
CAS号
4449-51-8
1178510-81-0
PubChem SID
162037467
PubChem CID
442972
CHEMBL
254129
Chemspider ID
391275
美国药典/FDA物质标识码
ZH658AJ192
维基百科标题
Cyclopamine

数据来源

数据来源

所有数据来源 商品来源 非商品来源

理论计算性质

理论计算性质

JChem
Acid pKa 18.204288  质子受体
质子供体 LogD (pH = 5.5) 0.5760557 
LogD (pH = 7.4) 1.2571619  Log P 3.7964666 
摩尔折射率 122.1691 cm3 极化性 48.454803 Å3
极化表面积 41.49 Å2 可自由旋转的化学键
里宾斯基五规则 true 

分子性质

分子性质

理化性质 安全信息 药理学性质 产品相关信息 生物活性(PubChem)
溶解度
Chloroform expand 查看数据来源
DMSO expand 查看数据来源
DMSO (1mg/200 μL expand 查看数据来源
heated to 70°C) expand 查看数据来源
Hot Methanol expand 查看数据来源
外观
White Solid expand 查看数据来源
熔点
236-238°C expand 查看数据来源
保存条件
-20°C expand 查看数据来源
-20°C Freezer expand 查看数据来源
MSDS下载
下载链接 expand 查看数据来源
作用靶点
Hedgehog expand 查看数据来源
成盐信息
Free Base expand 查看数据来源
质检报告
下载链接 expand 查看数据来源

详细说明

详细说明

Selleck Chemicals Selleck Chemicals Wikipedia Wikipedia TRC TRC
Selleck Chemicals -  S1146 external link
Research Area
Description Cancer
Biological Activity
Description Cyclopamine is a specific Hedgehog (Hh) signaling pathway antagonist of Smoothened (Smo) with IC50 of 46 nM.
Targets Smoothened (Smo)
IC50 46 nM [1]
In Vitro Cyclopamine inhibits the Hedgehog signaling pathway with an IC50 of 46 nM, and blocks the activity of human Smo receptor expressed in CHO-K1 cells in [3H]Hh-Ag binding assay with an IC50 of 280 nM. [1] Cyclopamine significantly inhibits Hedgehog pathway activity in a dose-dependent manner in gut-derived tumor cell lines expressing Patched (PTCH) mRNA, and induces growth inhibition of those tumor cell lines by 75-95% at the concentration of 3 μM, but ineffective towards the colon tumor cells without PTCH mRNA expression, suggesting the effects of Cyclopamine treatment are Hedgehog pathway related rather than generally cytotoxic. [2] By blocking Hedgehog signaling through direct interaction with Smo, Cyclopamine (10 μM) inhibits the proliferation of SMOhigh Cyclopamine-responsive cell lines L3.6sl and Panc 05.04 by 75-80%, and increases the apoptosis by 2.5- to 3.5-fold, without affecting the BxPC3-SMOlow cell line. [3] Cyclopamine treatment significantly decreases of Snail mRNA and increasea E-cadherin transcripts in the E3LZ10.7 cell line. Independent of inhibition of cell growth, Cyclopamine treatment significantly inhibits the invasive phenotype of Hedgehog-dependent L3.6pl cells, causing a >500-fold reduction in the number of transmigrating cells, but not that of the Hedgehog-independent cell line Panc-1. [4]
In Vivo Administration of Cyclopamine at dose of 50 mg/kg/day for 22 days eradicates the HUCCT1 xenografts in mice with no obvious adverse effects. [2] Cyclopamine treatment at dose of 1.2 mg for 7 days induces significant apoptosis of tumor cells and decreases the tumor mass by 50-60% in Panc 05.04- and L3.6sl-derived tumors, respectively, but not in the BxPC3-SMOlow tumors. [3] Administration of Cyclopamine alone profoundly inhibits tumor metastases in xenografts of E3LZ10.7 and L3.6pl, and completely abrogates metastases when in combination of gemcitabine. [4]
Clinical Trials
Features
Protocol
Kinase Assay [1]
Hedgehog cell assay This assay measures the end stage of the Hh signaling pathway, that is, the transcriptional modulation of Gli, using Luciferase as readout (Gli-Luc assay). Cyclopamine is prepared for assay by serial dilution in DMSO and then added to empty assay plates. TM3Hh12 cells (TM3 cells containing Hh-responsive reporter gene construct pTA-8xGli-Luc) are resuspended in F12 Ham’s/DMEM (1:1) containing 5% FBS and 15 mM Hepes pH 7.3, added to assay plates and incubated with Cyclopamine for approximately 30 minutes at 37 °C in 5% CO2. 1 nM Hh-Ag 1.5 is then added to assay plates and incubated at 37 °C in the presence of 5% CO2. After 48 hours, either Bright-Glo or MTS reagent is added to the assay plates and luminescence or absorbance at 492 nm is determined. IC50 value, defined as the inflection point of the logistic curve, is determined by non-linear regression of the Gli-driven luciferase luminescence or absorbance signal from MTS assay vs log10 (concentration) of Cyclopamine using the R statistical software package.
Cell Assay [2]
Cell Lines SEG1, OE33, KYAE, KYSE180, SNU1, AGS, SNU16, NCI-N-87, HUCCT1, PANC1, PL5, PL6, BXPC3, HS766T, KYSE150, GBD1, DLD1, and HCT116
Concentrations Dissolved in DMSO, final concentration 3 μM
Incubation Time 4 days
Methods Cells are exposed to Cyclopamine in 96-well plates. Cell viability is measured by MTS (soluble tetrazolium salt) assay. Viable cell mass is determined by optical density measurements at 490 nm (OD490) at 2 and 4 days using the CellTiter96 colorimetric assay. Relative growth is calculated as OD (day 4)﹣OD (day 2)/OD (day 2).
Animal Study [2]
Animal Models Athymic (nude) mice inoculated subcutaneously with HUCCT1 cells
Formulation Dissolved in DMSO, and diluted in saline
Doses 50 mg/kg/day
Administration Subcutaneous injection
References
[1] Peukert S, et al. Bioorg Med Chem Lett, 2009, 19(2), 328-331.
[2] Berman DM, et al. Nature, 2003, 425(6960), 846-851.
[3] Thayer SP, et al. Nature, 2003, 425(6960), 851-856.
[4] Feldmann G, et al. Cancer Res, 2007, 67(5), 2187-2196.
Toronto Research Chemicals -  C988400 external link
Cyclopamine antibacterial properties. Cyclopamine demonstrates teratogenic properties and has been shown to reverse effects of oncogenic mutations in Smoothened and Patched.Solubility: 1mg of Cyclopamine dissolves in 0.2ml DMSO with heating to approximate
Toronto Research Chemicals -  C988405 external link
Cyclopamine tartrate salt for cancer treatment. It is effective in inhibiting hedgehog signaling and stem cell functions.

参考文献

参考文献

供应商提供 Google Scholar IconGoogle Scholar PubMed iconPubMed Google Books IconGoogle Books
正在搜索,请耐心等待...(如果遇到网页错误或者长时间没有结果,请刷新页面[F5])

专利

专利

PubChem iconPubChem Patent Google Patent Search IconGoogle Patent

互联网资源

互联网资源

百度图标百度 google iconGoogle