Structure of WAY-262611
CAS No.: 1123231-07-1
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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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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.
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Keywords: Rolipram ; Phosphodiesterase ; Ligamentum Flavum hypertrophy ; ERK1/2 ; Fibrosis ; TGF-β1
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Phosphodiesterase 4 Inhibitor Plays An Anti-fibrosis Effect in Ligamentum Flavum Fibroblasts
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.
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Keywords: Phosphodiesterase ; Ligamentum flavum ; Fibrosis ; TGF‐β1
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| 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 |
| GHS Pictogram: |
|
| Signal Word: | Warning |
| Hazard Statements: | H302-H315-H319-H335 |
| Precautionary Statements: | P261-P305+P351+P338 |
Tags: WAY-262611 | BML-WN110 | Benzene Compounds | β-catenin | Organic Building Blocks | Notch Signaling Pathway | Parkinson'S Disease and Alzheimer'S Disease | Stem Cells | Wnt Signaling Pathway | 1123231-07-1
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| P285 | In case of inadequate ventilation wear respiratory protection. |
| P231 + P232 | Handle under inert gas. Protect from moisture. |
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| Code | Phrase |
| P301 | IF SWALLOWED: |
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| P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
| P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
| P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
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| P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
| P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
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| P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
| P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
| P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
| P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
| P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
| P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
| P370 + P376 | In case of fire: Stop leak if safe to Do so. |
| P370 + P378 | In case of fire: |
| P370 + P380 | In case of fire: Evacuate area. |
| P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
| P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
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| P401 | |
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| P410 | Protect from sunlight. |
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| P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
| P413 | |
| P420 | Store away from other materials. |
| P422 | |
| P402 + P404 | Store in a dry place. Store in a closed container. |
| P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
| P403 + P235 | Store in a well-ventilated place. Keep cool. |
| P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
| P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
| P411 + P235 | Keep cool. |
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| P501 | Dispose of contents/container to ... |
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Physical hazards | |
| Code | Phrase |
| H200 | Unstable explosive |
| H201 | Explosive; mass explosion hazard |
| H202 | Explosive; severe projection hazard |
| H203 | Explosive; fire, blast or projection hazard |
| H204 | Fire or projection hazard |
| H205 | May mass explode in fire |
| H220 | Extremely flammable gas |
| H221 | Flammable gas |
| H222 | Extremely flammable aerosol |
| H223 | Flammable aerosol |
| H224 | Extremely flammable liquid and vapour |
| H225 | Highly flammable liquid and vapour |
| H226 | Flammable liquid and vapour |
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| H228 | Flammable solid |
| H229 | Pressurized container: may burst if heated |
| H230 | May react explosively even in the absence of air |
| H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
| H240 | Heating may cause an explosion |
| H241 | Heating may cause a fire or explosion |
| H242 | Heating may cause a fire |
| H250 | Catches fire spontaneously if exposed to air |
| H251 | Self-heating; may catch fire |
| H252 | Self-heating in large quantities; may catch fire |
| H260 | In contact with water releases flammable gases which may ignite spontaneously |
| H261 | In contact with water releases flammable gas |
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Health hazards | |
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| H300 | Fatal if swallowed |
| H301 | Toxic if swallowed |
| H302 | Harmful if swallowed |
| H303 | May be harmful if swallowed |
| H304 | May be fatal if swallowed and enters airways |
| H305 | May be harmful if swallowed and enters airways |
| H310 | Fatal in contact with skin |
| H311 | Toxic in contact with skin |
| H312 | Harmful in contact with skin |
| H313 | May be harmful in contact with skin |
| H314 | Causes severe skin burns and eye damage |
| H315 | Causes skin irritation |
| H316 | Causes mild skin irritation |
| H317 | May cause an allergic skin reaction |
| H318 | Causes serious eye damage |
| H319 | Causes serious eye irritation |
| H320 | Causes eye irritation |
| H330 | Fatal if inhaled |
| H331 | Toxic if inhaled |
| H332 | Harmful if inhaled |
| H333 | May be harmful if inhaled |
| H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
| H335 | May cause respiratory irritation |
| H336 | May cause drowsiness or dizziness |
| H340 | May cause genetic defects |
| H341 | Suspected of causing genetic defects |
| H350 | May cause cancer |
| H351 | Suspected of causing cancer |
| H360 | May damage fertility or the unborn child |
| H361 | Suspected of damaging fertility or the unborn child |
| H361d | Suspected of damaging the unborn child |
| H362 | May cause harm to breast-fed children |
| H370 | Causes damage to organs |
| H371 | May cause damage to organs |
| H372 | Causes damage to organs through prolonged or repeated exposure |
| H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
| Code | Phrase |
| H400 | Very toxic to aquatic life |
| H401 | Toxic to aquatic life |
| H402 | Harmful to aquatic life |
| H410 | Very toxic to aquatic life with long-lasting effects |
| H411 | Toxic to aquatic life with long-lasting effects |
| H412 | Harmful to aquatic life with long-lasting effects |
| H413 | May cause long-lasting harmful effects to aquatic life |
| H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
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