GNE 477 Property

Density 

1.51±0.1 g/cm3(Predicted)

storage temp. 

Desiccate at -20°C

solubility 

insoluble in H2O; insoluble in EtOH; ≥16.69 mg/mL in DMSO with gentle warming

form 

Powder

pka

4.22±0.10(Predicted)

color 

Light yellow to yellow

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H317May cause an allergic skin reaction

H319Causes serious eye irritation

Precautionary statements

P280Wear protective gloves/protective clothing/eye protection/face protection.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

GNE 477 Chemical Properties,Usage,Production

Biological Activity

gne-477 is a potent dual pi3k/mtor inhibitor. owing to the common association with oncogenic malignancies, the pi3k/akt/mtor signaling pathway is regarded as an attractive area of research for the identification of oral small molecule inhibitors.

in vitro

gne-477 was found to inhibit pi3k-α, β, δ, and γ with ic50s of 4, 86, 6, and 15 nm, respectively. [1].

in vivo

a direct comparison of gne-477 with its des-methyl analog revealed that the trend of reduced in vivo clearance in rats is also observed in dogs and mice. the clearance improvement was significant in dogs where the des-methyl analog was cleared at two-thirds the rate of hepatic blood flow while gne-477 had low clearance. in an study evaluating the tumor growth inhibition of a pc3 tumor xenograft10 over 14 days, stasis was achieved at a 20 mg/kg qd dose of gne-477 and significant inhibition was found with doses as low as 1 mg/kg qd. gne-477 was generally well tolerated during this study as shown by acceptable levels of weight loss comparable to that in the vehicle cohort [1].

IC 50

4 and 21 nmol/l for pi3k and mtor, respectively

References

[1] heffron tp,berry m,castanedo g,chang c,chuckowree i,dotson j,folkes a,gunzner j,lesnick jd,lewis c,mathieu s,nonomiya j,olivero a,pang j,peterson d,salphati l,sampath d,sideris s,sutherlin dp,tsui v,wan nc,wang s,wong s,zhu by. identification of gne-477, a potent and efficacious dual pi3k/mtor inhibitor. bioorg med chem lett.2010 apr 15;20(8):2408-11.