CAS |
4449-51-8 |
Chinese Name |
环巴胺 |
English Name |
Cyclopamine |
Synonyms |
11-Deoxojervine |
Molecular Formula |
C27H41NO2 |
Molecular Weight |
411.62 |
Solubility |
Soluble in DMSO ≥5mg/mL |
Purity |
HPLC≥98% |
Appearance |
White to off-white Solid |
Storage |
Powder:2-8℃,2 years;Insolvent(Mother Liquid):-20℃,6 months;-80℃,1 year |
MDL |
MFCD01735266 |
SMILES |
CC1=C2[C@@]([C@@]3([H])[C@]([C@@]4(C(C[C@@H](O)CC4)=CC3)C)([H])C2)([H])CC[C@@]15[C@@H]([C@@]6([H])[C@](C[C@H](C)CN6)([H])O5)C |
InChIKey |
QASFUMOKHFSJGL-LAFRSMQTSA-N |
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 |
PubChem CID |
442972 |
Target Point |
Hedgehog/Smoothened |
Passage |
Hedgehog;Stem Cells |
Background |
Cyclopamine is a specific Hedgehog signaling pathway antagonist |
Biological Activity |
Cyclopamine 是 Hedgehog 通路的拮抗剂, 在细胞实验中的 IC50 为 46 nM[1]。 |
IC50 |
IC50: 46nM (Hedgehog, in Hh cell assay) [1] |
In Vitro |
用小分子Hh抑制剂如HhAntag和天然产物Cyclopamine(均与Smo结合)治疗可诱导成神经管细胞瘤基因小鼠模型的肿瘤缓解[1]。环巴胺是一种Hedgehog(Hh)通路拮抗剂。环巴胺抑制细胞生长。环巴胺(3μM)抑制Hh通路活性和消化道肿瘤细胞系的生长与PTCHmRNA的表达相关[2]。 Cyclopamine是一种甾体生物碱,通过与Smo的直接相互作用抑制Hh信号传导[3]。 |
In Vivo |
环巴胺导致异种移植肿瘤持续消退。环巴胺治疗动物的肿瘤完全消退12天[2]。环巴胺(1.2 mg)治疗在移植入裸鼠后阻断人胰腺癌细胞的肿瘤形成[3]。 |
Cell Experiment |
将细胞在96孔板中一式三份培养在测定培养基中,在0h以正文中指出的浓度加入5E1单克隆抗体,ShhNp和/或环巴胺(3μM)。使用CellTiter96比色测定,通过在490nm(OD490)在2天和4天的光密度测量来确定活细胞质量。相对生长计算为OD(第4天)-OD(第2天)/ OD(第2天)[2]。 |
Animal Experiment |
小鼠[3]将总共0.1mL Hanks'平衡盐溶液和含有2×106个细胞的基质胶(1:1)皮下注射到CD-1裸鼠中。使肿瘤生长4天至最小体积125mm 3; 对所有受试者同时开始治疗。每天皮下注射小鼠皮下注射载体(三油酸甘油酯:乙醇4:1v / v)或环巴胺悬浮液(每小鼠1.2mg三油酸甘油酯:乙醇4:1v / v),持续7天。在治疗期结束时,从小鼠切下肿瘤,称重,然后在4℃下用4%多聚甲醛固定3小时,包埋在石蜡中并切片(6μm)。使用重组Tdt通过TUNEL鉴定凋亡细胞。然后将切片用曙红复染。从随机选择对应于两个对照和两个环巴胺处理的肿瘤的外部,中间和内部的区域的8×20-放大的视野。我们手动计算了TUNEL阳性细胞核的数量。进行苏木精/伊红染色。 |
Data Literature Source |
[1]. Peukert S, et al. Identification and structure-activity relationships of ortho-biphenyl carboxamides as potent Smoothened antagonists inhibiting the Hedgehog signaling pathway. Bioorg Med Chem Lett, 2009, 19 (2) , 328-331. [2]. Berman DM, et al. Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours. Nature, 2003, 425 (6960) , 846-851. [3]. Thayer SP, et al. Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis. Nature, 2003, 425 (6960) , 851-856. [4]. Ma W, et al. Reduced Smoothened level rescued Aβ-induced memory deficits and neuronal inflammation in animal models of Alzheimer's disease. J Genet Genomics. 2018 May 20; 45 (5) :237-246 |
Unit |
Bottle |
Specification |
5mg 10mM*1mL in DMSO 10mg 20mg |