GW788388

Names

[ Name ]:
GW788388

[Synonym ]:
N-(oxan-4-yl)-4-[4-(5-pyridin-2-yl-1H-pyrazol-4-yl)pyridin-2-yl]benzamide
4-{4-[5-(2-Pyridinyl)-1H-pyrazol-4-yl]-2-pyridinyl}-N-(tetrahydro-2H-pyran-4-yl)benzamide
4-{4-[3-(pyridin-2-yl)-1H-pyrazol-4-yl]pyridin-2-yl}-N-(tetrahydro-2H-pyran-4-yl)benzamide
Benzamide, 4-[4-[5-(2-pyridinyl)-1H-pyrazol-4-yl]-2-pyridinyl]-N-(tetrahydro-2H-pyran-4-yl)-
GW788388

Biological Activity

[Description]:

GW788388 is a potent and selective inhibitor of ALK5 with IC50 of 18 nM, and also inhibits TGF-β type II receptor and activin type II receptor activities, without inhibiting BMP type II receptor.

[Related Catalog]:

Signaling Pathways >> TGF-beta/Smad >> TGF-β Receptor

Research Areas >> Cancer

[Target]

IC50: 18 nM (ALK5)

[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[3].

[Animal admin]

One week postsurgery, sham-operated (N=6) and infarcted animals (N=10) are randomized to treatment with the ALK5 inhibitor GW788388 (GSK) at a dosage of 50 mg/kg/day by gavage, which has been shown to significantly attenuate collagen overexpression in a rodent model of dimethylnitrosamine-induced liver disease. Untreated rats, that is, sham-operated (N=9) and MI animals (N=15), are gavaged with vehicle (1% carboxymethyl cellulose solution). Four animals with < 25% infarct size as determined postmortem by histology are excluded from further analyses.

[References]

[1]. Petersen M, et al. Oral administration of GW788388, an inhibitor of TGF-beta type I and II receptor kinases, decreases renal fibrosis. Kidney Int, 2008, 73(6), 705-715.

[2]. Tan SM, et al. Targeted inhibition of activin receptor-like kinase 5 signaling attenuates cardiac dysfunction following myocardial infarction. Am J Physiol Heart Circ Physiol, 2010, 298(5), H1415-1425.

[3]. Gellibert F, et al. 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, 49

[Related Small Molecules]

SB431542 | Galunisertib (LY2157299) | A 83-01 | LY2109761 | LDN193189 | RepSox | SB525334 | Vactosertib (TEW-7197) | DMH-1 | LY364947 | SB505124 | LY3200882 | H-Leu-Ser-Lys-Leu-NH2 trifluoroacetate salt | ITD-1 | K 02288

Chemical & Physical Properties

[ Density]:
1.3±0.1 g/cm3

[ Boiling Point ]:
683.2±55.0 °C at 760 mmHg

[ Molecular Formula ]:
C₂₅H₂₃N₅O₂

[ Molecular Weight ]:
425.482

[ Flash Point ]:
367.0±31.5 °C

[ Exact Mass ]:
425.185181

[ PSA ]:
92.79000

[ LogP ]:
1.88

[ Appearance of Characters ]:
white solid

[ Vapour Pressure ]:
0.0±2.1 mmHg at 25°C

[ Index of Refraction ]:
1.680

[ Storage condition ]:
-20℃

Safety Information

[ HS Code ]:
2934999090

Customs

[ HS Code ]: 2934999090

[ Summary ]:
2934999090. other heterocyclic compounds. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%