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Chemical Structure| 1123231-07-1 Chemical Structure| 1123231-07-1

Structure of WAY-262611
CAS No.: 1123231-07-1

Chemical Structure| 1123231-07-1

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WAY-262611 is an agonist of β-Catenin and can increase bone formation rate with EC50 of 0.63 μM.

Synonyms: BML-WN110; Dkk1 Inhibitor; WAY-262611 dihydrochloride WAY 262611 dihydrochloride

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Product Citations

Product Citations      Show More

Wu, Likang ; Xu, Lei ; Chen, Yu ; Xu, Guohua ; Guo, Qunfeng ; Meng, Depeng , et al.

Abstract: Background: Fibrosis is an important factor and process of ligamentum flavum hypertrophy. The expression of phosphodiesterase family (PDE) is related to inflammation and fibrosis. This article studied the expression of PDE in hypertrophic ligamentum flavum fibroblasts and investigated whether inhibition of PDE4 activity can play an anti-fibrotic effect. Methods: Samples of clinical hypertrophic ligamentum flavum were collected and patients with lumbar disc herniations as a control group. The collagenase digestion method is used to separate fibroblasts. qPCR is used to detect the expression of PDE subtypes, type I collagen (Col I), type III collagen (Col III), fibronectin (FN1) and transforming growth factor β1 (TGF-β1). Recombinant TGF-β1 was used to stimulate fibroblasts to make a fibrotic cell model and treated with Rolipram. The morphology of the cells treated with drugs was observed by Sirius Red staining. Scratch the cells to observe their migration and proliferation. WB detects the expression of the above-mentioned multiple fibrotic proteins after drug treatment. Finally, combined with a variety of signaling pathway drugs, the signaling mechanism was studied. Results: Multiple PDE subtypes were expressed in ligamentum flavum fibroblasts. The expression of PDE4A and 4B was significantly up-regulated in the hypertrophic group. Using Rolipram to inhibit PDE4 activity, the expression of Col I and TGF-β1 in the hypertrophic group was inhibited. Col I recovered to the level of the control group. TGF-β1 was significantly inhibited, which was lower than the control group. Recombinant TGF-β1 stimulated fibroblasts to increase the expression of Col I/III, FN1 and TGF-β1, which was blocked by Rolipram. Rolipram restored the increased expression of p-ERK1/2 stimulated by TGF-β1. Conclusion: The expressions of PDE4A and 4B in the hypertrophic ligamentum flavum are increased, suggesting that it is related to the hypertrophy of the ligamentum flavum. Rolipram has a good anti-fibrosis effect after inhibiting the activity of PDE4. This is related to blocking the function of TGF-β1, specifically by restoring normal ERK1/2 signal.

Keywords: Rolipram ; Phosphodiesterase ; Ligamentum Flavum hypertrophy ; ERK1/2 ; Fibrosis ; TGF-β1

Purchased from AmBeed: 61413-54-5 ; ; ;

Wu, Likang ; Song, Guoqiang ;

Abstract: Objective: Phosphodiesterase 4 inhibitor has anti‐inflammatory and anti‐fibrosis effects. We applied Rolipram, a phosphodiesterase 4 inhibitor,to ligamentum flavum fibroblasts to investigate its anti‐fibrotic effect and involved signaling pathways. Methods: Transforming growth factor‐β1 (TGF‐β1) was used to stimulate fibroblasts of the ligamentum flavum to make a fibrotic cell model. Fibrotic cells were treated with Rolipram and WAY‐262611. Western blotting was used to detect the expression of TGF‐ β1, collagen I (Col I) and collagen III in the cells and to examine changes in β‐catenin signaling pathways. Results: TGF‐β1 stimulates fibroblast fibrosis and increase the expression of collagen I, collagen III and endogenous TGF‐β1. Rolipram blocks this change, which is related to the suppression of activated p‐β‐catenin. Conclusion: Rolipram has a good anti‐fibrosis effectin vitro, which may be beneficialto the treatment of ligamentum flavum hypertrophy. We propose a new idea here, but a lot of research is needed for its specific application.

Keywords: Phosphodiesterase ; Ligamentum flavum ; Fibrosis ; TGF‐β1

Purchased from AmBeed: 61413-54-5 ;

Alternative Products

Product Details of WAY-262611

CAS No. :1123231-07-1
Formula : C20H22N4
M.W : 318.42
SMILES Code : NCC1CCN(C2=NC=CC(C3=CC=C4C=CC=CC4=C3)=N2)CC1
Synonyms :
BML-WN110; Dkk1 Inhibitor; WAY-262611 dihydrochloride WAY 262611 dihydrochloride
MDL No. :MFCD20527803
InChI Key :QHLITPHIARVDJI-UHFFFAOYSA-N
Pubchem ID :25199517

Safety of WAY-262611

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Isoform Comparison

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

3.14mL

0.63mL

0.31mL

15.70mL

3.14mL

1.57mL

31.41mL

6.28mL

3.14mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

[1]Enochson L, Stenberg J, et al. GDF5 reduces MMP13 expression in human chondrocytes via DKK1 mediated canonical Wnt signaling inhibition. Osteoarthritis Cartilage. 2014 Apr;22(4):566-77.

[2]Pelletier JC, Lundquist JT 4th, et al. (1-(4-(Naphthalen-2-yl)pyrimidin-2-yl)piperidin-4-yl)methanamine: a wingless beta-catenin agonist that increases bone formation rate. J Med Chem. 2009 Nov 26;52(22):6962-5.

[3]Ahn VE, Chu ML, Choi HJ, Tran D, Abo A, Weis WI. Structural basis of Wnt signaling inhibition by Dickkopf binding to LRP5/6. Dev Cell. 2011 Nov 15;21(5):862-73. doi: 10.1016/j.devcel.2011.09.003. Epub 2011 Oct 13. PMID: 22000856; PMCID: PMC3215855.

[4]Niehrs C. Function and biological roles of the Dickkopf family of Wnt modulators. Oncogene. 2006 Dec 4;25(57):7469-81. doi: 10.1038/sj.onc.1210054. PMID: 17143291.

[5]Pelletier JC, Lundquist JT 4th, Gilbert AM, Alon N, Bex FJ, Bhat BM, Bursavich MG, Coleburn VE, Felix LA, Green DM, Green P, Hauze DB, Kharode YP, Lam HS, Lockhead SR, Magolda RL, Matteo JJ, Mehlmann JF, Milligan C, Murrills RJ, Pirrello J, Selim S, Sharp MC, Unwalla RJ, Vera MD, Wrobel JE, Yaworsky P, Bodine PV. (1-(4-(Naphthalen-2-yl)pyrimidin-2-yl)piperidin-4-yl)methanamine: a wingless beta-catenin agonist that increases bone formation rate. J Med Chem. 2009 Nov 26;52(22):6962-5. doi: 10.1021/jm9014197. PMID: 19856966.

[6]Choe JY, Hun Kim J, Park KY, Choi CH, Kim SK. Activation of dickkopf-1 and focal adhesion kinase pathway by tumour necrosis factor α induces enhanced migration of fibroblast-like synoviocytes in rheumatoid arthritis. Rheumatology (Oxford). 2016 May;55(5):928-38. doi: 10.1093/rheumatology/kev422. Epub 2015 Dec 29. PMID: 26715774.

 

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