Purmorphamine
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
Purmorphamine是第一个针对Smoothened蛋白开发的小分子激动剂[1]。Purmorphamine激活Hedgehog（Hh）信号通路，导致其下游靶基因的上调和下调，包括Gli1和Patched。Purmorphamine可用于治疗骨相关疾病和神经变性疾病[2]。
体外实验：Purmorphamine通过直接结合并激活Smoothened进而激活Hedgehog通路，与Smo拮抗剂cyclopamine竞争时IC50值大约为1.5 μM[1]。在多能C3H10T1/2细胞中，Purmorphamine是成骨的有效诱导剂。在C3H10T1/2细胞中，基于ALP表达评估purmorphamine的EC50值为1 μM。在3T3-L1细胞中，Purmorphamine（1 μM）与BMP-4（100 ng/mL）的组合使用增加ALP活性超过90倍[3]。3和5 μM的Purmorphamine给药第14天上调骨钙蛋白的水平（P ≤ 0.05）[4]。
在体实验：在皮下移植基于干细胞的构建体的大鼠中，与用地塞米松或水注射的大鼠相比，Purmorphamine上调ALP转录物（P ≤ 0.05）[4]。
参考文献：
Sinha S, Chen J K. Purmorphamine activates the Hedgehog pathway by targeting Smoothened[J]. Nature chemical biology, 2006, 2(1): 29.
Wu X, Walker J, Zhang J, et al. Purmorphamine induces osteogenesis by activation of the hedgehog signaling pathway[J]. Chemistry & biology, 2004, 11(9): 1229-1238.
Wu X, Ding S, Ding Q, et al. A small molecule with osteogenesis-inducing activity in multipotent mesenchymal progenitor cells[J]. Journal of the American Chemical Society, 2002, 124(49): 14520-14521.
Faghihi F, Eslaminejad M B, Nekookar A, et al. The effect of purmorphamine and sirolimus on osteogenic differentiation of human bone marrow-derived mesenchymal stem cells[J]. Biomedicine & Pharmacotherapy, 2013, 67(1): 31-38.
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 520.62 |
| Cas No. | 483367-10-8 |
| Formula | C31H32N6O2 |
| Solubility | insoluble in H2O; ≥1.82 mg/mL in EtOH with ultrasonic; ≥8.68 mg/mL in DMSO |
| Chemical Name | 9-cyclohexyl-N-(4-morpholin-4-ylphenyl)-2-naphthalen-1-yloxypurin-6-amine |
| SDF | Download SDF |
| Canonical SMILES | C1CCC(CC1)N2C=NC3=C2N=C(N=C3NC4=CC=C(C=C4)N5CCOCC5)OC6=CC=CC7=CC=CC=C76 |
| 运输条件 | 蓝冰运输或根据您的需求运输。 |
| 一般建议 | 不同厂家不同批次产品溶解度各有差异，仅做参考。若实验所需浓度过大至产品溶解极限，请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存，请尽快用完。 |
| 细胞实验: [1] | |
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细胞系 |
间充质干细胞(MSCs) |
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制备方法 |
该化合物在DMSO中的溶解度小于10 mM，若配制更高浓度的溶液，一般步骤如下：请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。 |
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反应条件 |
14 d；2 μM |
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实验结果 |
通过膜受体SMO和PTCH1以及转录因子GLI1和GLI2的基因表达，在第7天和14天评估hMSC中purmorphamine对Hh信号传导的调节。在第7天，SMO的基因表达上调（P ≤ 0.05），在14天，表达下调（P ≤ 0.05）。在第7天，PTCH1表达上调（P ≤ 0.05），在14天表达不受影响（P ≤ 0.05）。Purmorphamine在第7（P ≤ 0.05）和14天（P ≤ 0.05）上调GLI1和GLI2的表达。 |
| 动物实验: [2] | |
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动物模型 |
正常雄性Wistar 大鼠 |
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给药剂量 |
5 μM，s.c. |
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实验结果 |
将基于人间充质干细胞的构建体皮下移植到大鼠中。根据组织学切片，标记的细胞存在于支架内。基于实时PCR结果发现，在移植的细胞构建体中，人成骨细胞基因、ALP、骨钙蛋白、Runx-2和胶原蛋白I表达上调。 |
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注意事项 |
请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同，但仍处于实验系统误差的允许范围内。 |
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References: [1] Oliveira F S, Bellesini L S, Defino H L A, et al. Hedgehog signaling and osteoblast gene expression are regulated by purmorphamine in human mesenchymal stem cells[J]. Journal of cellular biochemistry, 2012, 113(1): 204-208. [2]Faghihi F, Baghaban Eslaminejad M, Nekookar A, et al. The effect of purmorphamine and sirolimus on osteogenic differentiation of human bone marrow-derived mesenchymal stem cells[J]. Biomedicine & Pharmacotherapy, 2013, 67(1): 31-38. |
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| Description | Purmorphamine is a blocker of BODIPY-cyclopamine binding to Smo with IC50 of ~ 1.5 μM and also is an inducer of osteoblast differentiation with EC50 of 1 μM. | |||||
| Targets | Smoothened | |||||
| IC50 | ~ 1.5 μM | |||||
质量控制和MSDS
- 批次:
化学结构
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