Purmorphamine

Names

[ Name ]:
Purmorphamine

[Synonym ]:
Purmorphamine
9H-Purin-6-amine, 9-cyclohexyl-N-[4-(4-morpholinyl)phenyl]-2-(1-naphthalenyloxy)-
9-Cyclohexyl-N-[4-(4-morpholinyl)phenyl]-2-(1-naphthalenyloxy)
9-cyclohexyl-N-(4-morpholin-4-ylphenyl)-2-naphthalen-1-yloxypurin-6-amine
9-Cyclohexyl-N-[4-(4-morpholinyl)phenyl]-2-(1-naphthyloxy)-9H-purin-6-amine
2-(1-Naphthoxy)-6-(4-morpholinoanilino)-9-cyclohexylpurine
9H-Purin-6-amine (9-cyclohexyl-N-[4-(4-morpholinyl)phenyl]-2-(1-naphthalenyloxy)

Biological Activity

[Description]:

Purmorphamine is a smoothened receptor agonist with an EC50 of 1 μM.

[Related Catalog]:

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> Stem Cell/Wnt >> Smo

Research Areas >> Neurological Disease

[Target]

IC50: 1.5 μM (Smoothened)

[In Vitro]

Purmorphamine (10, 20 μM) in combination with sirolimus significantly decreases cell numbers according to the MTT assay. Purmorphamine induces up-regulation of alkaline phosphatase activity and expression of RUNX-2 at day 14. Up-regulation of osteocalcin is detected at the 3 and 5 μM doses of purmorphamine on day 14 post-induction. Matrix mineralization remains unchanged in the presence or absence of purmorphamine[1]. Purmorphamine induces STAT3 phosphorylation in mouse ES cell line ES14 and mesenchymal stem cell line C3H10T1/2[2]. Purmorphamine up-regulates the expressionof markers of the osteoblast phenotype-ALP activity and bone-like nodule formationd-in human bonemarrow mesenchymal cells[3].

[Cell Assay]

To determine non-toxic doses of the small molecules, 5×105 passaged-3 human MSCs are seeded in each well of a six-well culture plate and incubated in expansion medium (as mentioned above) at 37°Cand 5% CO2. Two days later, the medium is exchanged with osteogenic medium (OM) that consisted of α-MEM supplemented with 10% FBS, 10 nM dexamethasone, 50 μg/mL ascorbic acid 2-phosphate, and 10 mM beta-glycerol phosphate. This OM is supplemented with different concentrations of purmorphamine (1, 3, 5, 10, and 20 μM) and sirolimus (0.1, 1, 10, 100, and 200 nM). The cultures are maintained for an additional two days and then assessed for the presence of viable cells with the MTT assay, by the addition of MTT solution (5 mg/mL in PBS) to the medium at a ratio of 1:5. Cells are then incubated at 37°C and 5% CO2. Two hours later, the medium is removed and 500 μL of DMSO is added to the treated cells in order to dissolve the formazone precipitate. The optical absorption rate is read at 570 nm. Cell viability is calculated as percent value relative to the control group which is only treated with OM.

[References]

[1]. F. Faghihia, et al. The effect of purmorphamine and sirolimus on osteogenic differentiation of human bone marrow-derived mesenchymal stem cells. Biomedicine & Pharmacotherapy. 2013, 67(1): 31-38.

[2]. Gu D, et al. A role for transcription factor STAT3 signaling in oncogene smoothened-driven carcinogenesis. J Biol Chem. 2012 Nov 2;287(45):38356-66.

[3]. Beloti MM, et al. Purmorphamine enhances osteogenic activity of human osteoblasts derived from bone marrow mesenchymal cells. Cell Biol Int. 2005 Jul;29(7):537-41.

[Related Small Molecules]

SAG.HCI | LDE225 (NVP-LDE225,Erismodegib) | PF-04449913 | Jervine | LY2940680 | BMS-833923 | LEQ506 | MK-4101 | MRT-83 | PF-5274857 | Saridegib

Chemical & Physical Properties

[ Density]:
1.4±0.1 g/cm3

[ Boiling Point ]:
790.3±70.0 °C at 760 mmHg

[ Melting Point ]:
210-212ºC

[ Molecular Formula ]:
C₃₁H₃₂N₆O₂

[ Molecular Weight ]:
520.625

[ Flash Point ]:
431.8±35.7 °C

[ Exact Mass ]:
520.258667

[ PSA ]:
77.33000

[ LogP ]:
4.52

[ Appearance of Characters ]:
white to beige

[ Vapour Pressure ]:
0.0±2.8 mmHg at 25°C

[ Index of Refraction ]:
1.711

[ Storage condition ]:
-20°C Freezer

[ Water Solubility ]:
DMSO: soluble5mg/mL, clear (warmed)

MSDS

Click to get detail MSDS

Safety Information

[ RIDADR ]:
NONH for all modes of transport

Articles

Co-ordinated brain and craniofacial development depend upon Patched1/XIAP regulation of cell survival.

Hum. Mol. Genet. 24(3) , 698-713, (2015)

Congenital brain and craniofacial defects often occur together as a consequence of their developmental dependency on common progenitor tissue interactions and signaling pathways during embryogenesis. ...

Susceptibility of human embryonic stem cell-derived neural cells to Japanese encephalitis virus infection.

PLoS ONE 9(12) , e114990, (2014)

Pluripotent human embryonic stem cells (hESCs) can be efficiently directed to become immature neuroepithelial precursor cells (NPCs) and functional mature neural cells, including neurotransmitter-secr...

Generation of neuropeptidergic hypothalamic neurons from human pluripotent stem cells.

Development 142(4) , 633-43, (2015)

Hypothalamic neurons orchestrate many essential physiological and behavioral processes via secreted neuropeptides, and are relevant to human diseases such as obesity, narcolepsy and infertility. We re...