GW788388
Catalog No.S2750
Molecular Weight(MW): 425.48
GW788388 is a potent and selective inhibitor of ALK5 with IC50 of 18 nM in a cell-free assay, also inhibits TGF-β type II receptor and activin type II receptor activities, but does not inhibit BMP type II receptor.
Cited by 1 Publication
1 Customer Review
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Combination treatment with GW788388 and IL-23 aiming to sustain Th17 cell levels increases spleen cell production of the inflammatory mediators IL-17 and TNF-a, the stimulatory mediators IL-2, IFN-g and RANTES, and the inhibitory mediator IL-10. Starting from Week 6 of 4NQO administration, when premalignant oral lesions were detectable on the tongue, mice were initiated on treatment with diluent, GW788388, IL-23 or both GW788388 and IL-23. After 2 months of these treatments, spleens were collected and cultured on anti-CD3 for 3 days. Supernatants were collected and used for measurement of the inflammatory mediators IL-17, TNF-a and IL-6 (a); stimulatory mediators IL-2, IFN-g and RANTES (b); and inhibitory mediators, TGF-b, IL-4 and IL-10 (c). *=p<0.05, **=p<0.01, ***=p<0.001.
Int J Cancer, 2016, 138(10):2487-98. GW788388 purchased from Selleck.
Purity & Quality Control
Choose Selective TGF-beta/Smad Inhibitors
Biological Activity
| Description | GW788388 is a potent and selective inhibitor of ALK5 with IC50 of 18 nM in a cell-free assay, also inhibits TGF-β type II receptor and activin type II receptor activities, but does not inhibit BMP type II receptor. | |||||||||||||||||||||||
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| Targets |
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| In vitro |
GW788388 shows anti-TGF-β activity with IC50 of 93 nM in cellular assay. [1] GW788388 shows some inhibitory to activin type II receptor (ActRII) but no inhibitory to bone morphogenic protein (BMP) type II receptor. GW788388 shows no toxicity in Namru murine mammary gland (NMuMG), MDA-MB-231, renal cell carcinoma (RCC)4, and U2OS cells at 4 nM to 15 μM. GW788388 blocks TGF-β-induced Smad activation and target gene expression, while decreasing epithelial-mesenchymal transitions and fibrogenesis. GW788388 inhibits ALK5, ALK4, ALK7 and TGF-β-mediated growth arrest. [2] |
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| Cell Data |
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| In vivo | GW788388 exhibits an adequate pharmacokinetic profile in rats (plasma clearance less than 40 mL/min/kg and half-life more than 2 hours). GW788388 significantly reduces the expression of collagen IA1 mRNA by 80% in a model of puromycin aminonucleoside-induced renal fibrosis at 10 mg/kg. [1] GW788388 attenuates TGF-β signalling and effectively reduces hallmarks of fibrogenesis in mice suffering from late-stage diabetic nephropathy at 2 mg/kg. [2] Treatment with GW788388 significantly attenuates systolic dysfunction in the myocardial infarction (MI) animals, together with the attenuation of the activated (phosphorylated) Smad2, α-smooth muscle actin, and collagen I in the noninfarct zone of MI rats. Cardiomyocyte hypertrophy in MI hearts is also attenuated by GW788388 inhibition. [3] GW788388 reduces the fibrotic response in bleomycin-injected animals at 2 mg/kg. [4] |
Protocol
| Kinase Assay: [1] |
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ALK5 Fluorescence Polarization Binding Assay: GW788388 binding to ALK5 is tested on purified recombinant GST−ALK5 (residues 198-503). Displacement of rhodamine green fluorescently labeled ATP competitive inhibitor by different concentrations of GW788388 is used to calculate a binding pIC50. GST−ALK5 is added to a buffer containing 62.5 mM N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid (Hepes), pH 7.5, 1 mM dithiothreitol (DTT), 12.5 mM MgCl2, 1.25 mM 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid (CHAPS), and 1 nM rhodamine green-labeled ligand so that the final ALK5 concentration is 10 nM based on active-site titration of the enzyme. The enzyme/ligand reagent (40 μL) is added to 384-well assay plates containing 1 μL of different concentrations of GW788388. The plates are read immediately on a LJL Acquest fluorescence reader with excitation, emission, and dichroic filters of 485, 530, and 505 nm, respectively. The fluorescence polarization for each well is calculated by the Acquest and is then imported into curve-fitting software for construction of concentration−response curves. |
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| Cell Research: [2] |
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| Animal Research: [1] |
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Solubility (25°C)
| In vitro | DMSO | 15 mg/mL (35.25 mM) |
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| Water | Insoluble | |
| Ethanol | Insoluble | |
| In vivo | Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): 30% PEG400+0.5% Tween80+5% propylene glycol For best results, use promptly after mixing. |
30 mg/mL |
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Chemical Information
| Molecular Weight | 425.48 |
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| Formula | C25H23N5O2 |
| CAS No. | 452342-67-5 |
| Storage | powder |
| in solvent | |
| Synonyms | N/A |
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