GW788388

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Chemical Structure| 452342-67-5 同义名 : -
CAS号 : 452342-67-5
货号 : A887665
分子式 : C25H23N5O2
纯度 : 98%
分子量 : 425.482
MDL号 : MFCD16038936
存储条件：

Pure form Sealed in dry,2-8°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 25 mg/mL(58.76 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

IP 5%DMSO+40%PEG400+5% tween80+H2O 5 mg/mL clear

生物活性
靶点

  • TGFβRI/ALK5

    ALK5, IC50:18 nM
描述 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].
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 16570917
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.35mL

0.47mL

0.23mL

11.75mL

2.35mL

1.18mL

23.50mL

4.70mL

2.35mL
参考文献

[1]Tan SM, Zhang Y, et al. Targeted inhibition of activin receptor-like kinase 5 signaling attenuates cardiac dysfunction following myocardial infarction. Am J Physiol Heart Circ Physiol. 2010 May;298(5):H1415-25.

[2]Petersen M, Thorikay M, et al. Oral administration of GW788388, an inhibitor of TGF-beta type I and II receptor kinases, decreases renal fibrosis. Kidney Int. 2008 Mar;73(6):705-15.

[3]Gellibert F, de Gouville AC, Woolven J, Mathews N, Nguyen VL, Bertho-Ruault C, Patikis A, Grygielko ET, Laping NJ, Huet S. 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 Apr 6;49(7):2210-21.

[4]Petersen M, Thorikay M, Deckers M, van Dinther M, Grygielko ET, Gellibert F, de Gouville AC, Huet S, ten Dijke P, Laping NJ. Oral administration of GW788388, an inhibitor of TGF-beta type I and II receptor kinases, decreases renal fibrosis. Kidney Int. 2008 Mar;73(6):705-15.

[5]Lagares D, García-Fernández RA, Jiménez CL, Magán-Marchal N, Busnadiego O, Lamas S, Rodríguez-Pascual F. Endothelin 1 contributes to the effect of transforming growth factor beta1 on wound repair and skin fibrosis. Arthritis Rheum. 2010 Mar;62(3):878-89.