452342-67-5

Basic information

• Product Name: GW788388
• Synonyms: 4-[4-[3-(Pyridin-2-yl)-1H-pyrazol-4-yl]pyridin-2-yl]-N-(tetrahydropyran-4-yl)benzamide;GW 788388;BenzaMide, 4-[4-[3-(2-pyridinyl)-1H-pyrazol-4-yl]-2-pyridinyl]-N-(tetrahydro-2H-pyran-4-yl)-;4-(4-(3-(Pyridin-2-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-N-(tetrahydro-2H-pyran-4-yl)benzamide;N-(oxan-4-yl)-4-{4-[3-(pyridin-2-yl)-1H-pyrazol-4-yl]pyridin-2-yl}benzaMide;GW 788388 4-[4-[3-(Pyridin-2-yl)-1H-pyrazol-4-yl]pyridin-2-yl]-N-(tetrahydropyran-4-yl)benzamide;GW 788388, >=98%
• CAS NO: 452342-67-5
• Molecular Formula: C25H23N5O2
• Molecular Weight: 425.48242
• Product Categories: Inhibitors;Smad;TGF-beta
• Mol File: 452342-67-5.mol
• Article Data: 0

Chemical Properties

• Appearance: /
• Density: 1.34
• Storage Temp.: 2-8°C
• Solubility: Soluble in DMSO (18 mg/ml with warming)
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 1 month.
• CAS DataBase Reference: GW788388(CAS DataBase Reference)
• NIST Chemistry Reference: GW788388(452342-67-5)
• EPA Substance Registry System: GW788388(452342-67-5)

Safety Data

• Hazardous Substances Data: 452342-67-5(Hazardous Substances Data)

Usage

Description

GW788388 is a selective inhibitor of transforming growth factor-β (TGF-β) type 1 receptor (TGFBR1 or ALK5), with an IC50 of 18 nM. It effectively inhibits the expression of collagen type I in cells and in mice when administered orally at 10 mg/kg once a day. GW788388 is known for its ability to reduce fibrosis-related features, such as tissue remodeling, increased expression of α-smooth muscle actin, and production of collagen I. Additionally, it blocks TGF-β-mediated production of VEGF by fibroblasts and subsequent angiogenesis in vitro. The inhibition of ALK5 signaling by GW788388 also leads to hypertrophy in femoral growth plates in rats. Compared to SB431542, GW788388 offers a significantly improved pharmacokinetic profile.

Uses

Used in Pharmaceutical Industry:
GW788388 is used as a TGF-beta type I receptor inhibitor for its potential therapeutic effects in treating fibrosis and related conditions. Its ability to reduce tissue remodeling and collagen production makes it a promising candidate for managing fibrosis in various tissues.
Used in Research Applications:
GW788388 is used as a research tool for studying the role of TGF-β signaling in cell growth, differentiation, and tissue repair. Its selective inhibition of the TGF-β type 1 receptor allows researchers to investigate the molecular mechanisms underlying fibrosis and other TGF-β related pathologies.
Used in Drug Development:
GW788388 is utilized in the development of new therapeutic agents targeting TGF-β signaling pathways. Its improved pharmacokinetic profile compared to SB431542 makes it a valuable compound for designing drugs with better efficacy and safety profiles for the treatment of fibrosis and other related diseases.

References

Gellibert et al. (2006), Discovery of 4-{4-[3-(pyridine-2-yl)-1H-pyrazol-4-yl}pyridine-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. 49 2210 Petersen et al. (2008), Oral administration of GW788388, an inhibitor of TGF-beta type I and II receptor kinases, decreases renal fibrosis; Kidney Int. 73 705 De Oliveira et al. (2012), Oral administration of GW788388, an inhibitor of transforming growth factor beta signaling, prevents heart fibrosis in Chagas disease; PLoS Negl. Trop. Dis. 6 e1696 Noma et al. (2008), The essential role of fibroblasts in esophageal squamous cell carcinoma-induced angiogenesis; Gastroenterology. 134 1981 Lho et al. (2021), Effects of TGF-? Receptor Inhibitor GW788388 on the Epithelial to Mesenchymal Transition of Peritoneal Mesothelial Cells; Int. J. Mol. Sci. 22 4739