Structure of SKL2001
CAS No.: 909089-13-0
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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.
SKL2001 is Wnt/β-catenin pathway agonist which interferes in the interaction of Axin/β-catenin.
Synonyms: Wnt Agonist II; SKL2001
4.5
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Effects of blue light-exposed retinal pigment epithelial cells on the process of ametropia
Dai, Xiaochan ; Tang, Zhimin ; Ju, Yahan ; Ni, Ni ; Gao, Huiqin ; Wang, Jiajing , et al.
Abstract: Ametropia is one of the most common ocular disorders worldwide, to which almost half of visual impairments are attributed. Growing evidence has linked the development of ametropia with ambient light, including blue light, which is ubiquitous in our surroundings and has the highest photonic energy among the visible spectrum. However, the underlying mechanism of blue light-mediated ametropia remains controversial and unclear. In the present study, our data demonstrated that exposure of the retinal pigment epithelium (RPE) to blue light elevated the levels of the vital ametropia-related factor type Ⅰ collagen (COL1) via β-catenin inhibition in scleral fibroblasts, leading to axial ametropia (hyperopic shift). Herein, our study provides evidence for the vital role of blue light-induced RPE dysfunction in the process of blue light-mediated ametropia, providing intriguing insights into ametropic aetiology and pathology by proposing a link among blue light, RPE dysfunction and ametropia.
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Keywords: Ametropia ; Blue light ; Retinal pigment epithelium ; Scleral fibroblasts ; Type I collagen ; β-catenin
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Wnt signaling regulates ipsilateral pathfinding in the zebrafish forebrain through Slit3
Zhang, Quan ; Zhang, Cuizhen ; Zhang, Changwen ; Peng, Gang ;
Abstract: Abstract—The nervous system relies upon correct interconnections to exert its normal function. During vertebrate embryonic development, highly stereotyped scaffolds of axon tracts are formed early in the brain to set the foundation for the neuronal interconnections. During zebrafish early development, anterior dorsal telencephalic (ADt) neurons extend axons along the ipsilateral supraoptic tract (SOT) and the contralateral anterior commissure (AC). Our previous study shows axonal outgrowths along the AC/SOT tracts are coordinated by the guidance molecules Dcc-Netrin and Robo2-Slit, but it is not known how the expressions of these guidance molecules are regulated in the forebrain tissues. Here we show ectopic activation of Wnt signaling abolishes the ipsilateral SOT originating from the ADt neurons. Further mechanistic studies show ectopic activation of Wnt signaling significantly reduces Slits’ expression, whilst mis-expression of Slit3 rescues SOT outgrowth. Together, our findings indicate Wnt signaling controls the ipsilateral axonal outgrowth through the regulation of slits’ expression in the zebrafish forebrain.
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Keywords: axonal pathfinding ; Wnt signaling ; Slit3 ; forebrain ; zebrafish
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| CAS No. : | 909089-13-0 |
| Formula : | C14H14N4O3 |
| M.W : | 286.29 |
| SMILES Code : | O=C(C1=NOC(C2=CC=CO2)=C1)NCCCN3C=CN=C3 |
| Synonyms : |
Wnt Agonist II; SKL2001
|
| MDL No. : | MFCD14733081 |
| InChI Key : | PQXINDBPUDNMPE-UHFFFAOYSA-N |
| Pubchem ID : | 16003447 |
| GHS Pictogram: |
|
| Signal Word: | Warning |
| Hazard Statements: | H302-H315-H319-H335 |
| Precautionary Statements: | P261-P305+P351+P338 |
In Vitro:
|
Cell Line
|
Concentration | Treated Time | Description | References |
| MLO-Y4 cells | 60 µM | 24 hours | Activate Wnt signaling pathway and promote osteoblast differentiation | Cells. 2022 Feb 28;11(5):831 |
| cultured blastema cells | 40 μM | 24 h | To test the effect of SKL2001 on Akt phosphorylation, it was found that SKL2001 treatment enhanced Akt phosphorylation. | Commun Biol. 2022 Sep 27;5(1):1018. |
| mouse primary chondrocytes | 40 μM | 15 h | SKL2001, as an agonist of the Wnt/β-catenin pathway, was used to reverse the effect of IL-1β on the Wnt/β-catenin pathway. The results showed that SKL2001 significantly inhibited the cell viability of microsphere-treated IL-1β-stimulated chondrocytes and increased cell apoptosis. | Mater Today Bio. 2024 Oct 16;29:101300. |
| THP-1 macrophages | 20 µM | 1 h | To verify the effect of SKL2001 on the expression of β-catenin and c-Myc in THP-1 macrophages, the results showed that SKL2001 increased the expression of β-catenin and c-Myc. | Int J Biol Sci. 2024 Jan 1;20(3):848-863. |
| CRC cells | 30 μM | 24 h | To investigate the role of β-catenin signaling in the regulation of TFAM expression in CRC cells, 30 μM SKL2001 was added into cell culture medium for 24h. The results showed that SKL2001 significantly upregulated the expression of TFAM. | Cancer Commun (Lond). 2021 Aug;41(8):695-714. |
| Human memory CD8+ T cells | 20 μM | 7 days | SKL2001 mildly suppressed cell proliferation, increased the expression of CD27, CD28, and CD62L, while decreasing the expression of KLRG1, indicating it generates more TCM cells through the Wnt pathway. | J Clin Invest. 2022 Jan 18;132(2):e140508. |
| Human memory CD8+ T cells | 20 μM | 7 days | SKL2001 significantly increased the proportion of IL-2+ cells and enhanced polyfunctionality, indicating it enhances the polyfunctionality of memory CD8+ T cells through the Wnt pathway. | J Clin Invest. 2022 Jan 18;132(2):e140508. |
Tags: SKL2001 | SKL 2001 | SKL-2001 | Wnt | β-catenin | Beta catenin | 909089-13-0
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| Code | Phrase |
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| P378 | |
| P380 | Evacuate area. |
| P381 | Eliminate all ignition sources if safe to do so. |
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| P391 | Collect spillage. Hazardous to the aquatic environment |
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| P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
| 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. |
| P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
| P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
| P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
| P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
| 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. |
| P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
| P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
| 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: |
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| 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. |
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Disposal | |
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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 |
| H227 | Combustible liquid |
| 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 |
| H270 | May cause or intensify fire; oxidizer |
| H271 | May cause fire or explosion; strong oxidizer |
| H272 | May intensify fire; oxidizer |
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| H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
| H290 | May be corrosive to metals |
Health hazards | |
| Code | Phrase |
| 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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