Home TGF-beta/Smad TGF-beta/Smad inhibitor GW788388 For research use only.

GW788388

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.

GW788388 Chemical Structure

GW788388 Chemical Structure

CAS No. 452342-67-5

Purity & Quality Control

GW788388 Related Products

Signaling Pathway

TGF-beta/Smad Signaling Pathways

TGF-beta/Smad Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
HepG2 cells Function assay Inhibition of TGF beta-induced transcription of firefly luciferase reporter gene in HepG2 cells, IC50=0.093 μM 16570917
HEK293 cells Function assay Inhibition of TGF-beta1 signaling in human HEK293 cells transfected with luciferase and FAST-2 gene expression vector A3-LUX after 16 hrs by luciferase reporter gene assay, IC50=0.446 μM 21783359
Click to View More Cell Line Experimental Data

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.
Targets
ALK5 [1]
(Cell-free assay)
18 nM
In vitro
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]
Kinase Assay 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.
Cell Research Cell lines Namru murine mammary gland (NMuMG), MDA-MB-231, renal cell carcinoma (RCC)4, and U2OS cells
Concentrations 4 nM - 15 μM
Incubation Time 72 hours
Method Cell viability/proliferation assays are done according to the manufactures instructions (CellTiter 96 Aqueous One Solution Cell Proliferation Assay). Viability and proliferation are measured after 72 hours GW788388 treatment in the presence or absence of TGF-β.
Experimental Result Images Methods Biomarkers Images PMID
Western blot p-SMAD3 / SMAD3 25527621
In Vivo
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]
Animal Research Animal Models Sprague-Dawley rats with dimethylnitrosamine- (DMN-) induced liver disease or puromycin aminonucleoside-induced renal fibrosis
Dosages 3 or 10 mg/kg
Administration Oral gavage

Chemical Information & Solubility

Molecular Weight 425.48 Formula

C25H23N5O2
CAS No. 452342-67-5 SDF Download GW788388 SDF
Smiles C1COCCC1NC(=O)C2=CC=C(C=C2)C3=NC=CC(=C3)C4=C(NN=C4)C5=CC=CC=N5
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 33 mg/mL ( (77.55 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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