GW788388

Catalog No.S2750 Batch:S275002

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Technical Data

Formula

C25H23N5O2
Molecular Weight 425.48 CAS No. 452342-67-5
Solubility (25°C)* In vitro DMSO 33 mg/mL (77.55 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

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 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]
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 (from reference)

Kinase Assay: [1]
  • 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 Assay: [2]
  • 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.
Animal Study: [1]
  • 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

Customer Product Validation

Data from [Data independently produced by , , Int J Cancer, 2016, 138(10):2487-98]

Data from [Data independently produced by , , Oncogenesis, 2017, 6(9):e382]

Selleck's GW788388 has been cited by 25 publications

BATF promotes extramedullary infiltration through TGF-β1/Smad/MMPs axis in acute myeloid leukemia [ Mol Carcinog, 2024, 10.1002/mc.23715] PubMed: 38477642
Crosstalk between protein kinase C α and transforming growth factor β signaling mediated by Runx2 in intestinal epithelial cells [ J Biol Chem, 2023, 299(4):103017] PubMed: 36791912
Engineering of immune checkpoints B7-H3 and CD155 enhances immune compatibility of MHC-I-/- iPSCs for β cell replacement [ Cell Rep, 2022, 40(13):111423] PubMed: 36170817
Establishment and characterization of immortalized sweat gland myoepithelial cells [ Sci Rep, 2022, 12(1):7] PubMed: 34997030
Tenascin-C immobilizes infiltrating T lymphocytes through CXCL12 promoting breast cancer progression [ EMBO Mol Med, 2021, 13(6):e13270] PubMed: 33988305
Therapeutic silencing of SMOC2 prevents kidney function loss in mouse model of chronic kidney disease [ iScience, 2021, 24(10):103193] PubMed: 34703992
A scalable 3D tissue culture pipeline to enable functional therapeutic screening for pulmonary fibrosis [ APL Bioeng, 2021, 5(4):046102] PubMed: 34805716
Diamond Blackfan anemia is mediated by hyperactive Nemo-like kinase [ Nat Commun, 2020, 11(1):3344] PubMed: 32620751
Tenascin-C Orchestrates an Immune-Suppressive Tumor Microenvironment in Oral Squamous Cell Carcinoma [ Cancer Immunol Res, 2020, 10.1158/2326-6066.CIR-20-0074] PubMed: 32665262
A novel human colon signet-ring cell carcinoma organoid line: establishment, characterization and application [ Carcinogenesis, 2020, 41(7):993-1004] PubMed: 31740922

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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