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    Purmorphamine是第一個(gè)針對(duì)Smoothened蛋白開發(fā)的小分子激動(dòng)劑, 能夠直接結(jié)合并激活Smo,阻斷BODIPY-cyclopamine與Smo結(jié)合。 Purmorphamine激活Hedgehog(Hh)信號(hào)通路,導(dǎo)致其下游靶基因Gli1和Patched上調(diào)或下調(diào),Purmorphamine可用于治療骨相關(guān)疾病和神經(jīng)變性疾病[1-2]。

Purmorphamine(2 μM;4 days) 可以在多能性間充質(zhì)祖細(xì)胞中誘導(dǎo)成骨作用[3]。Purmorphamine可以增強(qiáng)來源于骨髓間充質(zhì)細(xì)胞的人類成骨細(xì)胞的成骨活性,Purmorphamine(1, 2 or 3 μM;21days)不影響細(xì)胞增殖或存活,但可以增加堿性磷酸酶(ALP)活性和骨瘤結(jié)節(jié)形成 [4]。Purmorphamine(2 μM) 可以促進(jìn)人類牙髓干細(xì)胞(hDPSCs)在β-TCP上的附著、增殖和成骨分化作用[5]。Purmorphamine可以大幅抑制大鼠間充質(zhì)干細(xì)胞的增殖,同時(shí)增強(qiáng)并加速堿性磷酸酶活性和鈣沉淀,并增加骨蛋白和骨鈣素的表達(dá)[6]。

Purmorphamine(10 mg/kg;i.p.) 可以預(yù)防缺氧缺血性腦損傷(HI)。Purmorphamine對(duì)組織損失產(chǎn)生長(zhǎng)期保護(hù)效應(yīng),并在HI刺激后的14天和28天改善了神經(jīng)行為結(jié)果[7]。 Purmorphamine(1mg/kg;i.p.) 激活Sonic Hedgehog (SHH)信號(hào),在小鼠中減輕了LPS引起的炎癥反應(yīng)[8]。

產(chǎn)品性質(zhì)：

Cas No.:483367-10-8

別名:嘌呤胺

化學(xué)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

儲(chǔ)存條件:Store at -20°C

注意事項(xiàng)：

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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]. W?ltje M, B?bel 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.