GSK143 dihydrochloride
Based on 1 publication(s) in Google Scholar
GSK143 dihydrochloride is an orally active and highly selective spleen tyrosine kinase (SYK) inhibitor with a pIC50 of 7.5. GSK143 dihydrochloride inhibits phosphorylated Erk (pErk: pIC50=7.1). GSK143 dihydrochloride reduces inflammation and prevents recruitment of immune cells in the intestinal muscularis in mice.
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- Purity : 99.37%
- CAS No.: 2341796-81-2
- 화학식: C17H24Cl2N6O2
- 분자량:415.32
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보관:
4°C, sealed storage, away from moisture and light
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)
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Biological Activity
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Chemical Information
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용액&용해도
- Protocol
- 순도&문서
- References
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Help & FAQs
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Publications Citing Use of MedChemExpress (MCE) GSK143 dihydrochloride
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Biological Activity
제품 설명
IC50 & Target
pIC50: 7.5 (SYK) and 7.1 (pErk)[1]
In Vitro
GSK143 dihydrochloride (compound 20) inhibits ZAP-70 (pIC50=4.7), LCK (pIC50=5.3), LYN (pIC50=5.4), JAK1/2/3 (pIC50=5.8/5.8/5.7), Aurora B (pIC50=4.8), hWB (pIC50=6.6), hERG (pIC50=4.7)[1].
GSK143 dihydrochloride (10-10000 nM; every 24 hours for 3 days) has an IC50 of 323 nM in CLL cells. GSK 143 dihydrochloride (1 μM; 30 mins) abrogates early signalling events including SYK phosphorylation and calcium flux[2].
GSK143 dihydrochloride (0.1-10 μM; for 30 min) reduces cytokine expression in bone marrow derived macrophages in a concentration-dependent manner[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:Chronic lymphocytic leukaemia (CLL) cells
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Concentration:10, 100, 1000, 10000 nM
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Incubation Time:Every 24 hours for 3 days
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Result:Had an IC50 of 323 nM.
In Vivo
GSK143 (3, 10, 30, 100 mg/kg; oral; 1 hour before ovalbumin challenge) reduces the cutaneous reverse passive Arthus reaction in a dose dependent manner by approximately 50% and 70% at 10 mg/kg and 30 mg/kg, respectively[2].
GSK143 (iv of 1 mg/kg; po of 3 mg/kg) has a T1/2 of 4.2 hours, low clearance (16 mL/min/kg), moderate bioavailability of 30% and a Vss of 4.1 L/kg in rats[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Wild type C57NL/BL6 mice, 10-12 weeks old[3]
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Dosage:0.1, 1, 3, 10 mg/kg
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Administration:Orally; 1.5 hours before intestinal manipulation (IM)
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Result:Reduced inflammation and prevented recruitment of immune cells in the intestinal muscularis.
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Animal Model:Male CD rats (175-200 g)[1]
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Dosage:1 mg/kg of iv; 3 mg/kg of po (Pharmacokinetic Analysis)
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Administration:IV or PO
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Result:Had a T1/2 of 4.2 hours, low clearance (16 mL/min/kg), moderate bioavailability of 30% and a Vss of 4.1 L/kg.
Chemical Information
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CAS No. 2341796-81-2
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Appearance Solid
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분자량 415.32
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화학식 C17H24Cl2N6O2
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Color Off-white to light yellow
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SMILES
[H]Cl.[H]Cl.O=C(C1=CN=C(N[C@H]2[C@@H](N)COCC2)N=C1NC3=CC=C(C)C=C3)N
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선적
Room temperature in continental US; may vary elsewhere.
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보관
4°C, sealed storage, away from moisture and light
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)
Publications (1)
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Journal Impact Factor
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Most Recent
용액&용해도
In Vitro:
H2O : 100 mg/mL (240.78 mM; Need ultrasonic)
DMSO : ≥ 50 mg/mL (120.39 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
* "≥" means soluble, but saturation unknown.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (6.02 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (6.02 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Working solution concentration: 0.22 mg/mL
This product has good water solubility, please refer to the measured solubility data in water/PBS/Saline for details.
Protocol
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Research Protocol for Inflammation-related Diseases
The NLRP3 inflammasome is a cytosolic innate immune signaling platform that integrates priming signals and danger-signal activation to promote caspase-1 activation, maturation of IL-1β and IL-18, and gasdermin D-mediated pyroptotic cell death. The core experimental logic is to determine whether inflammatory disease phenotypes are driven by increased NLRP3 expression, ASC-containing inflammasome assembly, caspase-1 cleavage, GSDMD cleavage, and extracellular release of IL-1β/IL-18 rather than by nonspecific cell injury alone. The pathway is strongly linked to inflammation-related disease phenotypes because monosodium urate crystals activate NALP3/NLRP3 inflammasome signaling in gout-like crystal inflammation, cholesterol crystals activate NLRP3 inflammasomes in atherogenesis models, and DSS-induced intestinal inflammation has been reported to involve NLRP3 inflammasome activity. However, experimental colitis studies also show context-dependent protective effects of NLRP3 inflammasome co
순도&문서
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Data Sheet (281 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
References
[1]. John Liddle, et al. Discovery of GSK143, a Highly Potent, Selective and Orally Efficacious Spleen Tyrosine Kinase Inhibitor. Bioorg Med Chem Lett. 2011 Oct 15;21(20):6188-94. [Content Brief]
[2]. Abraham M Varghese, et al. Highly Selective SYK Inhibitor, GSK143, Abrogates Survival Signals in Chronic Lymphocytic Leukaemia. Br J Haematol. 2018 Sep;182(6):927-930. [Content Brief]
[3]. Sjoerd H W van Bree, et al. Inhibition of Spleen Tyrosine Kinase as Treatment of Postoperative Ileus. Gut. 2013 Nov;62(11):1581-90. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO / H2O | 1 mM | 2.4078 mL | 12.0389 mL | 24.0778 mL | 60.1945 mL |
| 5 mM | 0.4816 mL | 2.4078 mL | 4.8156 mL | 12.0389 mL | |
| 10 mM | 0.2408 mL | 1.2039 mL | 2.4078 mL | 6.0195 mL | |
| 15 mM | 0.1605 mL | 0.8026 mL | 1.6052 mL | 4.0130 mL | |
| 20 mM | 0.1204 mL | 0.6019 mL | 1.2039 mL | 3.0097 mL | |
| 25 mM | 0.0963 mL | 0.4816 mL | 0.9631 mL | 2.4078 mL | |
| 30 mM | 0.0803 mL | 0.4013 mL | 0.8026 mL | 2.0065 mL | |
| 40 mM | 0.0602 mL | 0.3010 mL | 0.6019 mL | 1.5049 mL | |
| 50 mM | 0.0482 mL | 0.2408 mL | 0.4816 mL | 1.2039 mL | |
| 60 mM | 0.0401 mL | 0.2006 mL | 0.4013 mL | 1.0032 mL | |
| 80 mM | 0.0301 mL | 0.1505 mL | 0.3010 mL | 0.7524 mL | |
| 100 mM | 0.0241 mL | 0.1204 mL | 0.2408 mL | 0.6019 mL |
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
GSK143 dihydrochloride Related Classifications
HY-12736A Related Classifications
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