||Stem Cell Molecule
||9-cyclohexyl-N-(4-morpholin-4-ylphenyl)-2-naphthalen-1-yloxypurin-6-amine; purmorphamine; Purmorphamine; 483367-10-8; 2-(1-Naphthoxy)-6-(4-morpholinoanilino)-9-cyclohexylpurine; UNII-PB12M2F8KY; Shh Signaling Antagonist VI; PB12M2F8KY; CHEMBL1221984; CHEBI:63053; C31H32N6O2; IN1132; 9-cyclohexyl-N-[4-(morpholin-4-yl)phenyl]-2-(naphthalen-1-yloxy)-9H-purin-6-amine; 9-cyclohexyl-N-(4-morpholin-4-ylphenyl)-2-naphthalen-1-yloxypurin-6-amine; 9-Cyclohexyl-N-[4-(4-morpholinyl)phenyl]-2-(1-naphthalenyloxy)-9H-purin-6-amine; 9-Cyclohexyl-N-(4-(4-morpholinyl)phenyl)-2-(1-naphthalenyloxy)-9H-purin-6-amine; Purmorphamine [MI]; MolMap_000073; AC1NR49A; MLS006010334; SCHEMBL1548273; CTK1D4950; AOB5391; DTXSID20415293; FYBHCRQFSFYWPY-UHFFFAOYSA-N; HMS3650O20; BDBM50324671; HSCI1_000224;
IN2207; NSC747596; ZINC14806830; AKOS024458218; 2- -6- -9-CYCLOHEXYLPURINE; CS-1135; LS41103; NSC-747596; RL03799; NCGC00344053-01; 4CA-1056; AK175828; BC600598; DA-05531; HE070984; HE345035; HY-15108; KB-80166; QC-10453; SMR004701397; AB0032036; X5299; Purmorphamine and Shh Signaling Antagonist VI; W-5393; BRD-K73397362-001-01-7; 2-(1-Napthoxy)-6-(4-morpholinoanilino)-9-cyclohexylpurine; 9-cyclohexyl-N-(4-morpholinophenyl)-2-(naphthalen-1-yloxy)-9H-purin-6-amine; 9-Cyclohexyl-N-[4-(morpholinyl)phenyl]-2-(1-naphthalenyloxy)-9H-purin-6-amine; 9H-Purin-6-amine, 9-cyclohexyl-N-(4-(4-morpholinyl)phenyl)-2-(1-naphthalenyloxy)-; 9-?CYCLOHEXYL-?N-?[4-?(MORPHOLINYL)PHENYL]-?2-?(1-?NAPHTHALENYLOXY)-?9H-?PURIN-?6-?AMINE
||Purmorphamine, under the IUPAC name 9-Cyclohexyl-N-[4-(4-morpholinyl)phenyl]-2-(1-naphthalenyloxy)-9H-purin-6-amine, is a cell-permeable 6,9-trisubstituted purine which directly binds and activates Smoothened (in HEK293T cell：IC50= ~ 1.5 μM ).So it has been shown to activate the Hedgehog (Hh) signaling pathway which is important for regulating embryonic patterning, stem cell renewal, and tissue regeneration.
In vitro: An activator of the hedgehog (Hh) signaling pathway by directly binds and activates Smoothened (in HEK293T cell：IC50= ~ 1.5 μM ).
In vivo: Purmorphamine up-regulates ALP expression in human mesenchymal stem cell-based constructs on rats.
1. Exploring stem cell biology with small molecules
Shuibing Chen, Simon Hilcove, Sheng Ding*, Mol. BioSyst., 2006, 2, 18–24
Purmorphamine, a 2,6,9-trisubstituted purine compound, was identified as a potent osteogenic differentiation inducing molecule through a high throughput chemical screen in C3H10T1/2 cells. Expression profiling of cells treated with purmorphamine in conjunction with systematic pathway analysis was used to reveal that the Hedgehog/Hh signaling pathway is the primary affected biological network and purmorphamine is a selective Hh pathway agonist, which was further confirmed by chemical epistasis using two different Hh pathway antagonists: cyclopamine that binds and inhibits Smoothened (Smo), and forskolin that activates protein kinase A (PKA), which converts Gli proteins to transcriptional repressors by phosphorylation. Furthermore, purmorphamine’s function as an Hh pathway agonist was also confirmed by its effects of proliferating primary adult neural stem cells, as well as acting with RA in the sequential fashion to induce motor neuron differentiation of mESCs.
2. Small-molecule modulators of the Sonic Hedgehog signaling pathway
Benjamin Z. Stanton, Lee F. Peng*, Mol. BioSyst., 2010, 6, 44–54
Robotnikinin is a synthetic small-molecule inhibitor of Shh signaling that acts upstream of Smo. To date, it is the only small-molecule inhibitor of Shh signaling that acts upstream of Smo. Robotnikinin inhibits Gli transcription in Shh-LIGHT2 cells stimulated with ShhN, but when the Smo agonists purmorphamine or SAG were co-administered, its inhibitory activity was abolished. The compound is therefore able to inhibit Gli transcription by targeting a protein upstream of Smo in the Shh signaling pathway in Shh-LIGHT2 cells. Robotnikinin reduced alkaline phosphatase activity in a concentration-dependent fashion in C3H10T1/2 cells stimulated with ShhN, but this trend was eliminated when purmorphamine was co-administered. Thus, the activity of robotnikinin is not dependent on a cell line or reporter construct. Robotnikinin was also tested in primary human-derived keratinocytes stimulated with Shh. After 30 hours of treatment, Gli1 and Gli2 mRNA levels were reduced in a dose-dependent fashion, but this inhibition was eliminated with co-treatment with purmorphamine or SAG. Robotnikinin is able to inhibit Shh pathway activity in both mouse and human-derived cells upstream of Smo.
3. An eﬃcient method for the synthesis of heteroaryl C–O bonds in the absence of added transition metal catalysts
Katie Walsh, Helen F. Sneddonb, Christopher J. Moody*, RSC Adv.,2014, 4,28072–28077
The formation of aryl and heteroaryl C–O bonds in organic chemistry is an important synthetic tool, with the aryl ether products present in a variety of both natural and synthetic bioactive molecules. Examples include purmorphamine, which activates the Hedgehog-signalling pathway, an important regulator of stem cell renewal and cancer growth, and bispyribac-sodium, which is used as a herbicide. Traditionally the formation of these aryl C–O bonds was performed using nucleophilic aromatic substitution (SNAr), however poor substrate scope and reactivity has led to more elaborate synthetic strategies. For instance, the palladium-catalysed Buchwald–Hartwig reaction, or modern copper-catalysed variants on the classical Ullmann reaction.