Product Description
GW788388 is a potent and selective inhibitor of ALK5 with IC50 of 18 nM, and also inhibits TGF-β type II receptor and activin type II receptor activities, without inhibiting BMP type II receptor.
IC50 & Target: IC50: 18 nM (ALK5)
In Vivo: GW788388 given orally for 5 weeks significantly reduces renal fibrosis and decreased the mRNA levels of key mediators of extracellular matrix deposition in kidneys in db/db mice[1]. GW788388 (50 mg/kg/day, p.o.) significantly attenuates systolic dysfunction in the MI animals, together with the attenuation of the activated (phosphorylated) Smad2 (P < 0.01), α-smooth muscle actin (P < 0.001), and collagen I (P < 0.05) in the noninfarct zone of MI rats[2]. GW788388 reduces the expression of collagen IA1 by 80% at a dose of 1 mg/kg twice a day (b.i.d.). GW788388 significantly reduces the expression of collagen IA1 mRNA when administered orally at 10 mg/kg once a day (u.i.d.) in a model of puromycin aminonucleoside-induced renal fibrosis[3].
Information
CAS No452342-67-5
FormulaC25H23N5O2
Clinical Informationclinicalinformation
PathwayTGF-beta/Smad
TargetTGF-β Receptor
Specifications
FormWhite to gray (Solid)
Purity / Grade97.61%
SolubilityDMSO : ≥ 48 mg/mL (112.81 mM)
SmilesO=C(C1=CC=C(C=C1)C2=NC=CC(C3=CNN=C3C4=NC=CC=C4)=C2)NC5CCOCC5
Misc Information
Storage InstructionStorage temp. 2-8°C
Observed Molecular Weight425.48
NotesBiological Activity:
GW788388 is a potent and selective inhibitor of ALK5 with IC50 of 18 nM, and also inhibits TGF-β type II receptor and activin type II receptor activities, without inhibiting BMP type II receptor. IC50 & Target: IC50: 18 nM (ALK5) In Vivo: GW788388 given orally for 5 weeks significantly reduces renal fibrosis and decreased the mRNA levels of key mediators of extracellular matrix deposition in kidneys in db/db mice[1]. GW788388 (50 mg/kg/day, p.o.) significantly attenuates systolic dysfunction in the MI animals, together with the attenuation of the activated (phosphorylated) Smad2 (P < 0.01), α-smooth muscle actin (P < 0.001), and collagen I (P < 0.05) in the noninfarct zone of MI rats[2]. GW788388 reduces the expression of collagen IA1 by 80% at a dose of 1 mg/kg twice a day (b.i.d.). GW788388 significantly reduces the expression of collagen IA1 mRNA when administered orally at 10 mg/kg once a day (u.i.d.) in a model of puromycin aminonucleoside-induced renal fibrosis[3].
References[1]. Petersen M, et al. Oral administration of GW788388, an inhibitor of TGF-beta type I and II receptor kinases, decreases renal fibrosis. Kidney Int, 2008,
73(6), 705-715.
[2]. Tan SM, et al. Targeted inhibition of activin receptor-like kinase 5 signaling attenuates cardiac dysfunction following myocardial infarction. Am J Physiol
Heart Circ Physiol, 2010, 298(5), H1415-1425.
[3]. Gellibert F, et al. Discovery of 4-<4-[3-(pyridin-2-yl)-1H-pyrazol-4-yl]pyridin-2-yl>-N-(tetrahydro-2H- pyran-4-yl)benzamide (GW788388): a potent,
selective, and orally active transforming growth factor-beta type I receptor inhibitor. J Med Chem. 2006, 49