Name: GW788388
Brand: Selleck Chemicals
SKU: S2750
Availability: InStock
Rating: 5 (25 reviews)

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Quality Control

Batch: Purity: 99.99%

99.99

Related Targets	PKC ROCK Bcr-Abl
Other TGF-beta/Smad Inhibitors	SB431542 LDN-193189 Galunisertib (LY2157299) LY2109761 RepSox (E-616452) A-83-01 Vactosertib (TEW-7197) SRI-011381 (C381) SB-525334 LDN-193189 Dihydrochloride

Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Activity Description
HepG2 cells	Function assay	Inhibition of TGF beta-induced transcription of firefly luciferase reporter gene in HepG2 cells, IC50=0.093 μM
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
Click to View More Cell Line Experimental Data

Solubility

In vitro
Batch:

DMSO : 33 mg/mL (77.55 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	30%PEG400 1 0.5%Tween80 2 5%propylene glycol Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	30.000mg/ml (70.51mM)	Taking the 1 mL working solution as an example, add 300 μL of 100 mg/ml clarified PEG400 stock solution to 5 μL of Tween80, mix evenly to clarify it; add 50 μL Propylene glycol to the above system, mix evenly to clarify it; then continue to add 645 μL ddH2O to adjust the volume. to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg

Average weight of animals: g

Dosing volume per animal: μL

Number of animals:

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.)

% DMSO

%

% Tween 80

% ddH₂O

% DMSO

+

%

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.

Chemical Information, Storage & Stability

Molecular Weight	425.48	Formula	C₂₅H₂₃N₅O₂	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	452342-67-5	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	C1COCCC1NC(=O)C2=CC=C(C=C2)C3=NC=CC(=C3)C4=C(NN=C4)C5=CC=CC=N5

Mechanism of Action

Targets/IC₅₀/Ki	ALK5 (Cell-free assay) 18 nM
In vitro	GW788388 shows anti-TGF-β activity with IC50 of 93 nM in cellular assay. This compound shows some inhibitory to activin type II receptor (ActRII) but no inhibitory to bone morphogenic protein (BMP) type II receptor. It 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. It blocks TGF-β-induced Smad activation and target gene expression, while decreasing epithelial-mesenchymal transitions and fibrogenesis. This chemical inhibits ALK5, ALK4, ALK7 and TGF-β-mediated growth arrest.
Kinase Assay	ALK5 Fluorescence Polarization Binding Assay
Kinase 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 this compound 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 this chemical. 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.
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). This compound significantly reduces the expression of collagen IA1 mRNA by 80% in a model of puromycin aminonucleoside-induced renal fibrosis at 10 mg/kg. It attenuates TGF-β signalling and effectively reduces hallmarks of fibrogenesis in mice suffering from late-stage diabetic nephropathy at 2 mg/kg. Treatment with this chemical 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 its inhibition. This agent reduces the fibrotic response in bleomycin-injected animals at 2 mg/kg.
References	[1] https://pubmed.ncbi.nlm.nih.gov/16570917/ [2] https://pubmed.ncbi.nlm.nih.gov/18075500/ [3] https://pubmed.ncbi.nlm.nih.gov/20154262/ [4] https://pubmed.ncbi.nlm.nih.gov/20131241/

Applications

Methods	Biomarkers	Images	PMID
Western blot	p-SMAD3 / SMAD3		25527621

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GW788388 TGF-beta/Smad inhibitor

Chemical Structure

Molecular Weight: 425.48