Purmorphamine

• CAT Number: I003702
• CAS Number: 483367-10-8
• Molecular Formula: C31H32N6O2
• Molecular Weight: 520.62
• Purity: ≥95%
• Target: Smoothened
• Solubility: 10 mM in DMSO
• Storage: Store at -20°C
• IC50: 1.5 uM
• IUPAC Name: 9-cyclohexyl-N-(4-morpholin-4-ylphenyl)-2-naphthalen-1-yloxypurin-6-amine
• InChI: InChI=1S/C31H32N6O2/c1-2-9-25(10-3-1)37-21-32-28-29(33-23-13-15-24(16-14-23)36-17-19-38-20-18-36)34-31(35-30(28)37)39-27-12-6-8-22-7-4-5-11-26(22)27/h4-8,11-16,21,25H,1-3,9-10,17-20H2,(H,33,34,35)
• InChIKey: FYBHCRQFSFYWPY-UHFFFAOYSA-N
• SMILES: C1CCC(CC1)N2C=NC3=C(N=C(N=C32)OC4=CC=CC5=CC=CC=C54)NC6=CC=C(C=C6)N7CCOCC7

Purmorphamine（Cat No.:I003702） is a compound that interacts directly with Smoothened (Smo), a key component of the Hedgehog signaling pathway. It functions by binding to Smo, inhibiting the binding of BODIPY-cyclopamine to Smo with an IC50 of approximately 1.5 μM. Additionally, purmorphamine acts as an inducer of osteoblast differentiation, promoting the formation of bone-forming cells. Its osteogenic activity is demonstrated by an EC50 of 1 μM, indicating its potential therapeutic application in promoting bone regeneration and treating bone-related disorders.

Reference

1. Biomed Pharmacother. 2013 Feb;67(1):31-8. doi: 10.1016/j.biopha.2012.10.004. Epub
2012 Nov 16.
The effect of purmorphamine and sirolimus on osteogenic differentiation of human
bone marrow-derived mesenchymal stem cells.
Faghihi F(1), Baghaban Eslaminejad M, Nekookar A, Najar M, Salekdeh GH.
Author information:
(1)Department of Stem Cells and Developmental Biology, Cell Science Research
Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran,
Iran.
Small molecules have been introduced as less expensive biologically active
compounds that can regulate different developmental phenomena. Purmorphamine and
sirolimus are two small molecules that, according to some studies, possess
certain osteomodulatory effects. This study was set out to highlight the
appropriate dose and response time of these small molecules on enhancement of
osteogenesis in human bone marrow-derived mesenchymal stem cells from early to
mid and late stages of differentiation. Alkaline phosphatase activity, matrix
mineralization and expression of osteoblast genes were quantitatively assessed in
vitro. For the in vivo study, we transplanted stem cell-based constructs
subcutaneously into rats, and treated them daily with the most promising doses of
the small molecule. The constructs were analyzed by real-time PCR and
histological staining. Our results showed that Sirolimus reduced osteogenic
differentiation of mesenchymal stem cells by decreasing alkaline phosphatase
activity at dose of 100nM after 14 days and mineralization of the matrix at 14
and 21 days post-induction. Purmorphamine induced up-regulation of alkaline
phosphatase activity and expression of RUNX-2 at day 14. Up-regulation of
osteocalcin was detected at the 3 and 5μM doses of purmorphamine on day 14
post-induction. Matrix mineralization remained unchanged in the presence or
absence of purmorphamine. This dose of small molecule also accelerated expression
of Alkaline phosphatase transcripts in vivo. In conclusion, sirolimus had an
inhibitory effect on osteogenic differentiation of human bone marrow-derived
mesenchymal stem cells; while purmorphamine, particularly at a dose of 3μM,
showed a promotive effect in vitro and in vivo.
Copyright © 2012 Elsevier Masson SAS. All rights reserved.
DOI: 10.1016/j.biopha.2012.10.004
PMID: 23228449 [Indexed for MEDLINE]
2. Nat Chem Biol. 2006 Jan;2(1):29-30. Epub 2005 Nov 20.
Purmorphamine activates the Hedgehog pathway by targeting Smoothened.
Sinha S(1), Chen JK.
Author information:
(1)Department of Molecular Pharmacology, Stanford University School of Medicine,
Stanford, California 94305, USA.
Comment in
Nat Chem Biol. 2006 Jan;2(1):10-1.
Hedgehog (Hh) signaling is an important regulator of embryonic patterning, tissue
regeneration, stem cell renewal and cancer growth. A purine derivative named
purmorphamine was previously found to activate the Hh pathway and affect
osteoblast differentiation through an unknown mechanism. We demonstrate here that
purmorphamine directly targets Smoothened, a critical component of the Hh
signaling pathway.
DOI: 10.1038/nchembio753
PMID: 16408088 [Indexed for MEDLINE]
3. Chem Biol. 2004 Sep;11(9):1229-38.
Purmorphamine induces osteogenesis by activation of the hedgehog signaling
pathway.
Wu X(1), Walker J, Zhang J, Ding S, Schultz PG.
Author information:
(1)Department of Chemistry and The Skaggs Institute for Chemical Biology, The
Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037,
USA.
Previously, a small molecule, purmorphamine, was identified that selectively
induces osteogenesis in multipotent mesenchymal progenitor cells. In order to
gain insights into the mechanism of action of purmorphamine, high-density
oligonucleotide microarrays were used to profile gene expression in multipotent
mesenchymal progenitor cells treated with either purmorphamine or bone
morphogenetic protein-4 (BMP-4). In contrast to BMP-4 treatment, purmorphamine
activates the Hedgehog (Hh) signaling pathway, resulting in the up- and
downregulation of its downstream target genes, including Gli1 and Patched.
Moreover, the known Hh signaling antagonists, cyclopamine and forskolin,
completely block the osteogenesis and Glimediated transcription induced by
purmorphamine. These results demonstrate that purmorphamine is a small molecule
agonist of Hedgehog signaling, and it may ultimately be useful in the treatment
of bone-related disease and neurodegenerative disease.
DOI: 10.1016/j.chembiol.2004.06.010
PMID: 15380183 [Indexed for MEDLINE]