Transforming growth factor β (TGF-β) type I receptor (ALK5) is a transmembrane serine/threonine kinase. ALK5 forms a heteromeric complex with type II TGF-beta receptors when bound to TGF-beta, transducing the TGF-beta signal from the cell surface to the cytoplasm. Thus, ALK5 participates in regulation of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis.
GW788388 is an ALK5 kinase inhibitor with IC50 of 18 nM[3]. NMuMG and MDA-MB-231 cells were treated with GW788388 at the concentrations of 1 μM, 5 μM and 10 μM or 2.5 μM, 5 μM and 10 μM, respectively，in the presence of TGF-β for 1 h and the results showed that GW788388 inhibited TGF-β induced Smad2 phosphorylation in a dose-dependent manner in both cell lines[4]. In a rat model of chemically induced renal fibrosis, GW788388 administration at the doses of 3 mg/kg or 10 mg/kg u.i.d. significantly decreased relative collagen IA1 mRNA levels[3]. In a renal fibrosis model using db/db mice, GW788388 given orally at the dose of 2 mg/kg/day for 5 weeks significantly reduced renal fibrosis and decreased the mRNA levels of key mediators of extracellular matrix deposition in kidneys[4]. In a mouse model of bleomycin-induced dermal fibrosis, GW788388 given i.p. at the dose of 2 mg/kg/day prevented the fibrotic response[5].
作用机制
GW788388 is an ATP competitive inhibitor of the kinase domain of ALK5[4].
GW788388 细胞研究
细胞系
浓度
检测类型
检测时间
活动说明
数据源
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
HepG2 cells
Function assay
Inhibition of TGF beta-induced transcription of firefly luciferase reporter gene in HepG2 cells, IC50=0.093 μM
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
HepG2 cells
Function assay
Inhibition of TGF beta-induced transcription of firefly luciferase reporter gene in HepG2 cells, IC50=0.093 μM
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