GW788388


Catalog No. size PriceQuantity
M6903-2 2mg solid $91
M6903-10 10mg solid $360

Description

Cas:452342-67-5

Product Information

GW788388 is a new TGF-beta type I receptor inhibitor with a much improved pharmacokinetic profile compared with SB431542. We studied its effect in vitro and found that it inhibited both the TGF-beta type I and type II receptor kinase activities, but not that of the related bone morphogenic protein type II receptor. Further, it blocked TGF-beta-induced Smad activation and target gene expression, while decreasing epithelial-mesenchymal transitions and fibrogenesis.

 

Chemical Formula: C25H23N5O2

 

Exact Mass: 425.18518

 

Molecular Weight: 425.48

 

Elemental Analysis: C, 70.57; H, 5.54; N, 16.46; O, 7.52

 

Chemical Name: 4-(4-(3-(pyridin-2-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-N-(tetrahydro-2H-pyran-4-yl)benzamide

 

InChi Key:

SAGZIBJAQGBRQA-UHFFFAOYSA-N

 

InChi Code: InChI=1S/C25H23N5O2/c31-25(29-20-9-13-32-14-10-20)18-6-4-17(5-7-18)23-15-19(8-12-27-23)21-16-28-30-24(21)22-3-1-2-11-26-22/h1-8,11-12,15-16,20H,9-10,13-14H2,(H,28,30)(H,29,31)

 

Smiles Code:

O=C(NC1CCOCC1)C2=CC=C(C3=NC=CC(C4=CNN=C4C5=NC=CC=C5)=C3)C=C2

 

 

Technical Data:

 

Appearance: solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934999090

 

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.

 

 

References

 

  1. Tan SM, Zhang Y, Connelly KA, Gilbert RE, Kelly DJ. 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. Epub 2010 Feb 12. PubMed PMID: 20154262.

 

  1. 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. PubMed PMID: 20131241.

 

  1. Noma K, Smalley KS, Lioni M, Naomoto Y, Tanaka N, El-Deiry W, King AJ, Nakagawa H, Herlyn M. The essential role of fibroblasts in esophageal squamous cell carcinoma-induced angiogenesis. Gastroenterology. 2008 Jun;134(7):1981-93. Epub 2008 Mar 4. PubMed PMID: 18439605; PubMed Central PMCID: PMC2562524.

 

  1. 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. Epub 2007 Dec 12. PubMed PMID: 18075500.

 

  1. Frazier K, Thomas R, Scicchitano M, Mirabile R, Boyce R, Zimmerman D, Grygielko E, Nold J, DeGouville AC, Huet S, Laping N, Gellibert F. Inhibition of ALK5 signaling induces physeal dysplasia in rats. Toxicol Pathol. 2007 Feb;35(2):284-95. PubMed PMID: 17366323.

 

Products are for research use only. Not for human use.

 

 

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