483367-10-8 Usage
Description
Purmorphamine is a 2,6,9-trisubstituted purine that promotes osteoblast differentiation and activates the Hedgehog signaling pathway by targeting the 7-transmembrane Smo receptor. It is a light tan solid and has potential therapeutic applications for bone diseases such as osteoporosis.
Uses
Used in Pharmaceutical Industry:
Purmorphamine is used as an activator of the hedgehog (Hh) signaling pathway for promoting osteoblast differentiation, which might be useful as a therapeutic agent for bone diseases such as osteoporosis.
Used in Research Applications:
Purmorphamine is used as a research tool for studying the consequences of upregulation of the Hedgehog signaling pathway, particularly in Tupfel long fin strain Zebrafish.
Used in Drug Development:
Purmorphamine is used as a chemical compound to activate the Hedgehog pathway by targeting Smoothened, which can be beneficial in the development of drugs targeting this pathway for various therapeutic applications.
Biochem/physiol Actions
Purmorphamine activates the Hedgehog (Hh) signaling pathway, directly binding to the Smoothened (Smo) receptor. In various studies, purmorphamine has been shown to induce osteoblast differentiation, generate cardiomyocytes from human embryonic stem cells, increase the neuronal differentiation of a human striatal neural stem cell line, and to differentiate human umbilical cord mesenchymal stem cells (hUCMSCs) into motoneurons.
in vitro
purmorphamine activated the hedgehog pathway by directly bound and activated smoothened with the ic50value of ~ 1.5 μm in competing with cyclopamine, a smo antagonist [1]. in multi-potent c3h10t1/2 cells, purmorphamine was a potent inducer of osteogenesis. in c3h10t1/2 cells, the ec50 values assessed based on alp expression for purmorphamine was 1 μm. purmorphamine (1 μm) in combination with bmp-4 (100 ng/ml) increased alp activity more than 90-fold in 3t3-l1 cells [3].administration of purmorphamine at 3 and 5 μm up-regulated the level of osteocalcin on day 14 (p ≤ 0.05)[4].
in vivo
in rats transplanted with stem cell-based constructs subcutaneously, treatment with purmorphamine tended to up-regulate alp transcripts when compared with those injected by either dexamethasone or injection water (p ≤ 0.05) [4].
References
1) Wu et al. (2002), A small molecule with osteogenesis-inducing activity in multipotent mesenchymal progenitor cells; J. Am. Chem. Soc., 124 14520
2) Wu et al. (2004), Purmorphamine induces osteogenesis by activation of the hedgehog signaling pathway; Chem. Biol. 11 1229
3) Sinha and Chen (2006), Purmorphamine activates the Hedgehog pathway by targeting Smoothened; Nat. Chem. Biol., 2 29
4) Kang et al. (2015), Reprogramming of mouse somatic cells into pluripotent stem-like cells using a combination of small molecules; Biomaterials, 35 7336
5) Zhang et al. (2015), Small Molecules Efficiently Reprogram Human Astroglial Cells into Functional Neurons; Cell Stem Cell 17 735
Check Digit Verification of cas no
The CAS Registry Mumber 483367-10-8 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 4,8,3,3,6 and 7 respectively; the second part has 2 digits, 1 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 483367-10:
(8*4)+(7*8)+(6*3)+(5*3)+(4*6)+(3*7)+(2*1)+(1*0)=168
168 % 10 = 8
So 483367-10-8 is a valid CAS Registry Number.
