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]。

产品性质：

Cas No.:483367-10-8

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

注意事项：

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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]. 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.