Purmorphamine是第一个针对Smoothened蛋白开发的小分子激动剂, 能够直接结合并激活Smo,阻断BODIPY-cyclopamine与Smo结合。
Cas No.:483367-10-8
Sample solution is provided at 25 µL, 10mM.
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Purmorphamine is the first small molecule agonist developed for Smoothened protein. Purmorphamine directly binds and activates Smoothened, blocking the binding of BODIPY-cyclopamine to Smo. Purmorphamine activates the Hedgehog(Hh) signaling pathway, resulting in up-regulation and down-regulation of its downstream target genes, including Gli1 and Patched Purmorphamine can be used to treat bone-related diseases and neurodegenerative diseases[1-2].
Purmorphamine(2 µM;4 days) induces osteogenesis in pluripotent mesenchymal progenitor cells[3]. Purmorphamine enhances osteogenic activity of human osteoblasts derived from bone marrow mesenchymal cells, Purmorphamine(1, 2 or 3 µM;21days) did not affect cell proliferation or viability, but increased ALP activity and bone-like nodule formation[4]. Purmorphamine(2 µM ) had a promotive effect on adhesion, proliferation and osteogenic differentiation of human dental pulp stem cells (hDPSCs) cultured on β-TCP[5]. Purmorphamine substantially suppressed proliferation, enhanced and accelerated alkaline phosphatase activity and calcium sedimentation and increased the expression of osteopontin and osteocalcin in rat mesenchymal stem cells[6].
Purmorphamine(10 mg/kg; i.p.) prevents Hypoxic-Ischemic(HI)-induced brain injury. Purmorphamine exerted long-term protective effects upon tissue loss and improved neurobehavioral outcomes as determined at 14 and 28 days post-HI insult[7].Purmorphamine(1mg/kg; i.p.) activated Sonic hedgehog (SHH) signal to attenuate LPS-induced inflammatory response in mice[8].
References:
[1]. Sinha S, Chen JK. Purmorphamine activates the Hedgehog pathway by targeting Smoothened. Nat Chem Biol. 2006 Jan;2(1):29-30. doi: 10.1038/nchembio753. Epub 2005 Nov 20. PMID: 16408088.
[2]. Faghihi F, Baghaban Eslaminejad M, et,al.The effect of purmorphamine and sirolimus on osteogenic differentiation of human bone marrow-derived mesenchymal stem cells. Biomed Pharmacother. 2013 Feb;67(1):31-8. doi: 10.1016/j.biopha.2012.10.004. Epub 2012 Nov 16. PMID: 23228449.
[3]. Wu X, Walker J, et,al.Purmorphamine induces osteogenesis by activation of the hedgehog signaling pathway. Chem Biol. 2004 Sep;11(9):1229-38. doi: 10.1016/j.chembiol.2004.06.010. PMID: 15380183.
[4]. Beloti MM, Bellesini LS, et,al. Purmorphamine enhances osteogenic activity of human osteoblasts derived from bone marrow mesenchymal cells. Cell Biol Int. 2005 Jul;29(7):537-41. doi: 10.1016/j.cellbi.2005.02.007. PMID: 15979909.
[5]. Rezia Rad M, Khojaste M, et,al. Purmorphamine increased adhesion, proliferation and expression of osteoblast phenotype markers of human dental pulp stem cells cultured on beta-tricalcium phosphate. Biomed Pharmacother. 2016 Aug;82:432-8. doi: 10.1016/j.biopha.2016.05.016. Epub 2016 Jun 1. PMID: 27470382.
[6]. WÖltje M, BÖbel M, et,al. Purmorphamine and oxysterols accelerate and promote osteogenic differentiation of mesenchymal stem cells in vitro. In Vivo. 2015 Mar-Apr;29(2):247-54. PMID: 25792653.
[7]. Liu D, Bai X, et,al. Purmorphamine Attenuates Neuro-Inflammation and Synaptic Impairments After Hypoxic-Ischemic Injury in Neonatal Mice via Shh Signaling. Front Pharmacol. 2020 Mar 4;11:204. doi: 10.3389/fphar.2020.00204. PMID: 32194421; PMCID: PMC7064623.
[8]. Shao S, Wang GL, et,al.Activation of Sonic hedgehog signal by Purmorphamine, in a mouse model of Parkinson's disease, protects dopaminergic neurons and attenuates inflammatory response by mediating PI3K/AKt signaling pathway. Mol Med Rep. 2017 Aug;16(2):1269-1277. doi: 10.3892/mmr.2017.6751. Epub 2017 Jun 9. PMID: 28627590; PMCID: PMC5562000.
Purmorphamine是第一个针对Smoothened蛋白开发的小分子激动剂, 能够直接结合并激活Smo,阻断BODIPY-cyclopamine与Smo结合。 Purmorphamine激活Hedgehog(Hh)信号通路,导致其下游靶基因Gli1和Patched上调或下调,Purmorphamine可用于治疗骨相关疾病和神经变性疾病[1-2]。
Purmorphamine(2 µM;4 days) 可以在多能性间充质祖细胞中诱导成骨作用[3]。Purmorphamine可以增强来源于骨髓间充质细胞的人类成骨细胞的成骨活性,Purmorphamine(1, 2 or 3 µM;21days)不影响细胞增殖或存活,但可以增加碱性磷酸酶(ALP)活性和骨瘤结节形成 [4]。Purmorphamine(2 µM) 可以促进人类牙髓干细胞(hDPSCs)在β-TCP上的附着、增殖和成骨分化作用[5]。Purmorphamine可以大幅抑制大鼠间充质干细胞的增殖,同时增强并加速碱性磷酸酶活性和钙沉淀,并增加骨蛋白和骨钙素的表达[6]。
Purmorphamine(10 mg/kg;i.p.) 可以预防缺氧缺血性脑损伤(HI)。Purmorphamine对组织损失产生长期保护效应,并在HI刺激后的14天和28天改善了神经行为结果[7]。 Purmorphamine(1mg/kg;i.p.) 激活Sonic Hedgehog (SHH)信号,在小鼠中减轻了LPS引起的炎症反应[8]。
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Kinase experiment[1]: |
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Preparation method |
Smo binding experiments were performed using BODIPY-Cyclopamine and cells overexpressing Smo. Two days after transfection of HEK 293T cells, the cells were incubated at 37 ℃for 1 hour with DMEM medium containing BODIPY-Cyclopamine and varying concentrations of Purmorphamine (0, 1.5, or 5μM) (1 mL per well). The overexpressed Smo cells were then washed with 1xPBS buffer (1 mL per well), placed in a medium containing DAPI, observed using fluorescence microscopy, and binding detection was performed using fixed cells. Smo-overexpressing HEK293T cells were fixed at room temperature with 3% paraformaldehyde dissolved in 1 xPBS buffer (1 mL per well) for 10 minutes, then treated with 1 xPBS buffer (1 mL per well) containing 10 mm of glycerine and 0.2% sodium azide for 5 minutes with 1 xPBS buffer (1 ml per well). Cells were washed and then treated with a medium containing Purmorphamine at room temperature for 4 hours. |
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Reaction Conditions |
0, 1.5, or 5μM Purmorphamine |
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Applications |
Purmorphamine directly binds and activates Smoothened, blocking BODIPY-cyclopamine binding to Smo, with an IC50 of about 1.5 μM in HEK293T cells. |
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Cell experiment [2]: |
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Cell lines |
C3H10T1/2 cells |
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Preparation method |
Cells were treated with 2 μM of purmorphamine or 0.5% DMSO control for 4 days. |
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Reaction Conditions |
2 μM purmorphamine;4 days |
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Applications |
Purmorphamine induces osteogenesis in pluripotent mesenchymal progenitor cells. |
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Animal experiment [3]: |
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Animal models |
Male C57BL/6J mouse ( HI injury) |
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Dosage form |
10 mg/kg purmorphamine, i.p. |
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Applications |
Purmorphamine prevents Hypoxic-Ischemic(HI)-induced brain injury. |
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References: [1]. Sinha S, Chen JK. Purmorphamine activates the Hedgehog pathway by targeting Smoothened. Nat Chem Biol. 2006 Jan;2(1):29-30. doi: 10.1038/nchembio753. Epub 2005 Nov 20. PMID: 16408088. [2].Wu X, Walker J,et,al. Purmorphamine induces osteogenesis by activation of the hedgehog signaling pathway. Chem Biol. 2004 Sep;11(9):1229-38. doi: 10.1016/j.chembiol.2004.06.010. PMID: 15380183. [3]. Liu D, Bai X, et,al. Purmorphamine Attenuates Neuro-Inflammation and Synaptic Impairments After Hypoxic-Ischemic Injury in Neonatal Mice via Shh Signaling. Front Pharmacol. 2020 Mar 4;11:204. doi: 10.3389/fphar.2020.00204. PMID: 32194421; PMCID: PMC7064623. |
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| Cas No. | 483367-10-8 | SDF | |
| 别名 | 嘌呤胺 | ||
| 化学名 | 9-cyclohexyl-N-(4-morpholin-4-ylphenyl)-2-naphthalen-1-yloxypurin-6-amine | ||
| Canonical SMILES | C1CCC(CC1)N2C=NC3=C2N=C(N=C3NC4=CC=C(C=C4)N5CCOCC5)OC6=CC=CC7=CC=CC=C76 | ||
| 分子式 | C31H32N6O2 | 分子量 | 520.62 |
| 溶解度 | ≥ 8.7mg/mL in DMSO, ≥ 1.82 mg/mL in EtOH with ultrasonic | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.9208 mL | 9.6039 mL | 19.2079 mL |
| 5 mM | 384.2 μL | 1.9208 mL | 3.8416 mL |
| 10 mM | 192.1 μL | 960.4 μL | 1.9208 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
