GW788388

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.

Product information

CAS Number: 452342-67-5

Molecular Weight: 425.48

Formula: C25H23N5O2

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

Smiles: O=C(NC1CCOCC1)C1C=CC(=CC=1)C1=CC(=CC=N1)C1=CNN=C1C1=CC=CC=N1

InChiKey: SAGZIBJAQGBRQA-UHFFFAOYSA-N

InChi: 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)

Technical Data

Appearance: Solid Power.

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

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

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.
2. 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.
3. 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.