ArtNr |
S2750-5 |
Hersteller |
Selleckchem
|
CAS-Nr. |
452342-67-5 |
Menge |
5 mg |
Kategorie |
|
Typ |
Inhibitors |
Specific against |
other |
ECLASS 10.1 |
32160490 |
ECLASS 11.0 |
32160490 |
UNSPSC |
12000000 |
Alias |
452342-67-5' |
Similar products |
GW788388 |
Lieferbar |
|
Administration |
Oral gavage |
Animal Models |
Sprague–Dawley rats with dimethylnitrosamine- (DMN-) induced liver disease or puromycin aminonucleoside-induced renal fibrosis |
Cell lines |
Namru murine mammary gland (NMuMG), MDA-MB-231, renal cell carcinoma (RCC)4, and U2OS cells |
Chemical Name |
4-(4-(3-(pyridin-2-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-N-(tetrahydro-2H-pyran-4-yl)benzamide |
Concentrations |
4 nM - 15 uM |
Description |
GW788388 is a potent and selective inhibitor of ALK5 with IC50 of 18 nM. |
Dosages |
3 or 10 mg/kg |
Formulation |
4% DMSO and 96% [0.5% HPMC/5% Tween/20%HCl (1 M) in NaH2PO4 (0.1 M) |
IC50 |
18 nM [1], 18 nM [1], 18 nM [1], 18 nM [1], 18 nM [1], 18 nM [1] |
In vitro |
GW788388 shows anti-TGF-beta 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 uM. GW788388 blocks TGF-beta-induced Smad activation and target gene expression, while decreasing epithelial–mesenchymal transitions and fibrogenesis. GW788388 inhibits ALK5, ALK4, ALK7 and TGF-beta-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-beta 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, alpha-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] |
Incubation Time |
72 hours |
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 uL) is added to 384-well assay plates containing 1 uL 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. |
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-beta. |
Molecular Weight (MW) |
425, 48 |
Picture ChemicalStructure Description |
GW788388 Chemical Structure |
Solubility (25C) |
DMSO 33 mg/mL, Water <1 mg/mL, Ethanol <1 mg/mL |
Storage |
2 years -20CPowder, 2 weeks4Cin DMSO, 2 months-80Cin DMSO |
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