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Purity: ≥98%
GW788388 (GW-788388; GW 788388) is an inhibitor of ALK5/TGF-β type II receptor with potential antifibrotic activity. It inhibits ALK5/TGF-β type II receptor with an IC50 of 18 nM in a cell-free assay.
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For five weeks, db/db mice receiving oral GW788388 treatment had a significant reduction in renal fibrosis and mRNA levels of important mediators of renal extracellular matrix deposition [1]. In rats with myocardial infarction, GW788388 (50 mg/kg/day, p.o.) significantly reduced contractile dysfunction while also attenuating activated (phosphorylated) Smad2 (P < 0.01), α-smooth muscle actin (P < 0.001), and Collagen I (P < 0.05) [2]. Taken twice daily (bid), GW788388 lowers collagen IA1 expression by 80%. The dosage is 1 mg/kg. In a puromycin aminonucleoside-induced renal fibrosis model, GW788388, when given orally at 10 mg/kg once daily (uid), significantly decreased the expression of collagen IA1 mRNA [3].
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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), 705-715.
[2]. Tan SM, et al. Targeted inhibition of activin receptor-like kinase 5 signaling attenuates cardiac dysfunction following myocardial infarction. Am J Physiol Heart Circ Physiol, 2010, 298(5), H1415-1425. [3]. Gellibert F, et al. Discovery of 4-{4-[3-(pyridin-2-yl)-1H-pyrazol-4-yl]pyridin-2-yl}-N-(tetrahydro-2H- pyran-4-yl)benzamide (GW788388): a potent, selective, and orally active transforming growth factor-beta type I receptor inhibitor. J Med Chem. 2006, 49 |
| Molecular Formula |
C25H23N5O2
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| Molecular Weight |
425.48
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| CAS # |
452342-67-5
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| SMILES |
O1C([H])([H])C([H])([H])C([H])(C([H])([H])C1([H])[H])N([H])C(C1C([H])=C([H])C(C2C([H])=C(C([H])=C([H])N=2)C2C([H])=NN([H])C=2C2=C([H])C([H])=C([H])C([H])=N2)=C([H])C=1[H])=O
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.88 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.88 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.88 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 30% PEG400+0.5% Tween80+5% Propylene glycol: 30 mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3503 mL | 11.7514 mL | 23.5029 mL | |
| 5 mM | 0.4701 mL | 2.3503 mL | 4.7006 mL | |
| 10 mM | 0.2350 mL | 1.1751 mL | 2.3503 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 GW788388 inhibits both ALK5 and TβRII.Kidney Int.2008 Mar;73(6):705-15. |
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 GW788388 inhibits TGF-β-induced Smad activation dose-dependently.Kidney Int.2008 Mar;73(6):705-15. |
 GW788388 inhibits ALK5, ALK4, and ALK7 in a dose-dependent manner and has no effect on ALK2, ALK3, and ALK6.Kidney Int.2008 Mar;73(6):705-15. |
 GW788388 inhibits TGF-β-mediated EMT and apoptosis.(a) NMuMG cell proliferation measured after 72 h drug stimulation with dilution series of GW788388 (GW) (squares) and SB431542 (SB) (triangles) in the presence (closed symbols) or absence (open symbols) of TGF-β. (b) Phase-contrast images of TGF-β-induced EMT±GW788388 after 48 h stimulation. (c) Immunofluorescent staining of actin stress fiber formation after 48 h drug and TGF-β stimulation.Kidney Int.2008 Mar;73(6):705-15. |
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 TGF-β-induced EMT is inhibited by GW788388.Western blot analysis of epithelial and mesenchymal protein markers in RCC4/VHL (a) and NMuMG (b) cells after 48 h of drug and TGF-β stimulation. Control is DMSO-treated cells. β-Actin was used as a loading control. (c) Reverse transcriptase-polymerase chain reaction semi-quantitative analysis of SNAIL, PAI-1, E-cadherin, and FN in NMuMG cells after GW788388 (GW) or SB431542 (SB) treatment and TGF-β stimulation for 48 hKidney Int.2008 Mar;73(6):705-15. |
GW788388 inhibits the TGF-β-induced fibrotic responsein vitro. |
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