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Purmorphamine

现货
Catalog No.
A8228
Hedgehog激动剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,100.00
现货
5mg
¥ 1,000.00
现货
25mg
¥ 3,230.00
现货

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Background

Purmorphamine is the first small-molecule agonist developed for the protein Smoothened [1]. Purmorphamine activates the Hedgehog (Hh) signaling pathway, resulting in the up- and downregulation of its downstream target genes, including Gli1 and Patched. Purmorphamine may ultimately be useful in the treatment of bone-related disease andneurodegenerative disease [2].

In vitro: Purmorphamine activated the Hedgehog pathway by directly bound and activated Smoothened with the IC50value of ~ 1.5 μM in competing with cyclopamine, a Smo antagonist [1]. In multi-potent C3H10T1/2 cells, purmorphamine was a potent inducer of osteogenesis. In C3H10T1/2 cells, The EC50 values assessed based on ALP expression for purmorphamine was 1 μM. Purmorphamine (1 μM) in combination with BMP-4 (100 ng/mL) increased ALP activity more than 90-fold in 3T3-L1 cells [3].Administration of purmorphamine at 3 and 5 μM up-regulated the level of osteocalcin on day 14 (P ≤ 0.05)[4].

In vivo: In rats transplanted with stem cell-based constructs subcutaneously, treatment with purmorphamine tended to up-regulate ALP transcripts when compared with those injected by either dexamethasone or injection water (P ≤ 0.05) [4].

References:
[1]. Sinha S, Chen J K. Purmorphamine activates the Hedgehog pathway by targeting Smoothened[J]. Nature chemical biology, 2006, 2(1): 29.
[2]. 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.
[3]. 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.
[4]. 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.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt520.62
Cas No.483367-10-8
FormulaC31H32N6O2
Solubility≥8.7mg/mL in DMSO, ≥1.82 mg/mL in EtOH with ultrasonic, <2.27 mg/mL in H2O
Chemical Name9-cyclohexyl-N-(4-morpholin-4-ylphenyl)-2-naphthalen-1-yloxypurin-6-amine
SDFDownload SDF
Canonical SMILESC1CCC(CC1)N2C=NC3=C2N=C(N=C3NC4=CC=C(C=C4)N5CCOCC5)OC6=CC=CC7=CC=CC=C76
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。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。

试验操作

细胞实验: [1]

细胞系

间充质干细胞(MSCs)

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。

反应条件

14 d;2 μM

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]

动物模型

正常雄性Wistar 大鼠

给药剂量

5 μM,s.c.

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。

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。

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.

生物活性

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

化学结构

Purmorphamine

相关生物数据

Purmorphamine

相关生物数据

Purmorphamine