GW788388 |
| Catalog No.GC11878 |
GW788388 est un inhibiteur puissant et sélectif d'ALK5 avec une IC50 de 18 nM, et inhibe également les activités du récepteur TGF-β de type II et du récepteur d'activine de type II, sans inhiber le récepteur BMP de type II.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 452342-67-5
Sample solution is provided at 25 µL, 10mM.
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GW788388 is a selective inhibitor of ALK5 with IC50 value of 18 nM [1].
Transforming growth factor beta (TGF-beta) type I receptor (ALK5) is the receptor of TGF-beta and plays an important role in transducing the TGF-beta signal from the cell surface to the cytoplasm [2 ].
GW788388 is a potent TGF-beta type I receptor inhibitor and has a much improved pharmacokinetic profile compared with the reported TGF-beta type I receptor inhibitor SB431542. When tested with human embryonic kidney 293T cells transfected with ALK5, TβRII, BMPRII or ActRII, GW788388 exhibited specific inhibitory function on the autophosphorylation of ALK5 and TβRII, while had some extent to ActRII and had no effect on BMPRII. Further, using Namrumurine mammary gland (NMuMG), MDA-MB-231, renal cell carcinoma (RCC)4 and U2OS cell lines, GW788388 treatment inhibited TGF-β-induced Smad2 phosphorylation, inhibited TGF-β-induced EMT and growth, and TGF-β-induced fibrotic responses [1]. In ESCC/fibroblast/HMVEC co-culture model, GW788388 treatment (1 μM) resulted in a complete reversal of vascular network formation that indicated GW788388 blocked ESCC-induced neoangiogenesis [3].
In 6-month-old db/db mouse model of spontaneous diabetic nephropathy, administration of GW788388 at the dose of 2 mg/kg/day orally for 5 weeks attenuated renal fibrosis without any side-effect [1]. In 10-week Sprague-Dawley rats model, oral administration of GW788388 (100-1000 mg/kg/day) for 4 days induced the thickness of femoral physis in a dose-dependent manner and severity of physeal changes , as well as subphyseal hyperostosis, increased with duration of dosing progressing from minimal to moderate in rats given 300 mg/kg/day for 10 days [2].
References:
[1]. Petersen, M., et al., Oral administration of GW788388, an inhibitor of TGF-beta type I and II receptor kinases, decreases renal fibrosis. Kidney Int, 2008. 73(6): p. 705-15.
[2]. Frazier, K., et al., Inhibition of ALK5 signaling induces physeal dysplasia in rats. Toxicol Pathol, 2007. 35(2): p. 284-95.
[3]. Noma, K., et al., The essential role of fibroblasts in esophageal squamous cell carcinoma-induced angiogenesis. Gastroenterology, 2008. 134(7): p. 1981-93.
| Cell experiment [1]: | |
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Cell lines |
NMuMG and MDA-MD-231 cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20 °C for several months. |
|
Reaction Conditions |
1, 2.5, 5 or 10 μM; 1 hr |
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Applications |
In NMuMG and MDA-MD-231 cells, GW788388 dose-dependently inhibited TGF-β-induced Smad2 phosphorylation. In addition, TGF-β-mediated Smad1/5 phosphorylation, which requires ALK5 and TbRII, was also inhibited by GW788388. |
| Animal experiment [1]: | |
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Animal models |
A db/db mouse model of spontaneous diabetic nephropathy |
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Dosage form |
2 mg/kg/day; p.o.; for 5 weeks |
|
Applications |
In a db/db mouse model of spontaneous diabetic nephropathy, GW788388 significantly reduced collagen deposits, substantially improved glomerulopathy (marked by mesangial matrix expansion, mesangial hypertrophy, proliferation, and glomerular basement membrane thickening), as well as decreased urinary albumin concentrations. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Petersen, M., et al., Oral administration of GW788388, an inhibitor of TGF-beta type I and II receptor kinases, decreases renal fibrosis. Kidney Int, 2008. 73(6): p. 705-15. |
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| Cas No. | 452342-67-5 | SDF | |
| Chemical Name | N-(oxan-4-yl)-4-[4-(5-pyridin-2-yl-1H-pyrazol-4-yl)pyridin-2-yl]benzamide | ||
| Canonical SMILES | C1COCCC1NC(=O)C2=CC=C(C=C2)C3=NC=CC(=C3)C4=C(NN=C4)C5=CC=CC=N5 | ||
| Formula | C25H23N5O2 | M.Wt | 425.49 |
| Solubility | ≥ 21.25mg/mL in DMSO | Storage | Store at -20℃ |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.3502 mL | 11.7512 mL | 23.5023 mL |
| 5 mM | 0.47 mL | 2.3502 mL | 4.7005 mL |
| 10 mM | 0.235 mL | 1.1751 mL | 2.3502 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 28 reference(s) in Google Scholar.)
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