1032754-81-6 Usage
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.
Check Digit Verification of cas no
The CAS Registry Mumber 1032754-81-6 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,0,3,2,7,5 and 4 respectively; the second part has 2 digits, 8 and 1 respectively.
Calculate Digit Verification of CAS Registry Number 1032754-81:
(9*1)+(8*0)+(7*3)+(6*2)+(5*7)+(4*5)+(3*4)+(2*8)+(1*1)=126
126 % 10 = 6
So 1032754-81-6 is a valid CAS Registry Number.
1032754-81-6Relevant articles and documents
Identification of GNE-477, a potent and efficacious dual PI3K/mTOR inhibitor
Heffron, Timothy P.,Berry, Megan,Castanedo, Georgette,Chang, Christine,Chuckowree, Irina,Dotson, Jennafer,Folkes, Adrian,Gunzner, Janet,Lesnick, John D.,Lewis, Cristina,Mathieu, Simon,Nonomiya, Jim,Olivero, Alan,Pang, Jodie,Peterson, David,Salphati, Laurent,Sampath, Deepak,Sideris, Steve,Sutherlin, Daniel P.,Tsui, Vickie,Wan, Nan Chi,Wang, Shumei,Wong, Susan,Zhu, Bing-yan
scheme or table, p. 2408 - 2411 (2010/07/16)
Efforts to identify potent small molecule inhibitors of PI3 kinase and mTOR led to the discovery of the exceptionally potent 6-aryl morpholino thienopyrimidine 6. In an effort to reduce the melting point in analogs of 6, the thienopyrimidine was modified by the addition of a methyl group to disrupt planarity. This modification resulted in a general improvement in in vivo clearance. This discovery led to the identification of GNE-477 (8), a potent and efficacious dual PI3K/mTOR inhibitor.
