1394076-92-6 Usage
Biological Activity
gne-317 is a potent inhibitor of pi3k [1].phosphatidylinositol-4,5-bisphosphate 3-kinase (pi3k) are a series of enzymes and play an important role in cell growth, proliferation, differentiation, survival, motility and intracellular trafficking.in the gl261 cell line, gne-317 showed cytotoxic activity [2].in mouse brain, gne-317(50 mg/kg) significantly inhibited pakt, p4ebp1 and ps6 by 80%, 84%, and 92% respectively, which were downstream markers of the pi3k/mtor pathway. in u87, gs2 and gbm10 tumor-bearing mice, gne-317 inhibited tumor growth by 90%, 50% and a survival benefit, respectively [1]. in c57b6/j mice inoculated with gl261-gfp-luc cells, the concentrations of gne-317 in the normal brain, tumor core and rim were not significantly different. in tumor-bearing mice, gne-317 significantly reduced the levels of p-aktser473, p-s6ser235/236 and p-4ebp1thr37/46 within the tumor [2]. in u87 and gs2 glioblastoma multiforme (gbm) models, gne-317 was uniformly distributed in the brain. the brain-to-plasma ratios for gne-317 were greater than 1, in agreement with the brain penetration properties of gne-317 [3].
references
[1]. salphati l, heffron tp, alicke b, et al. targeting the pi3k pathway in the brain--efficacy of a pi3k inhibitor optimized to cross the blood-brain barrier. clin cancer res, 2012, 18(22): 6239-6248.[2]. becker cm, oberoi rk, mcfarren sj, et al. decreased affinity for efflux transporters increases brain penetrance and molecular targeting of a pi3k/mtor inhibitor in a mouse model of glioblastoma. neuro oncol, 2015, pii: nov081.[3]. salphati l, shahidi-latham s, quiason c, et al. distribution of the phosphatidylinositol 3-kinase inhibitors pictilisib (gdc-0941) and gne-317 in u87 and gs2 intracranial glioblastoma models-assessment by matrix-assisted laser desorption ionization imaging. drug metab dispos, 2014, 42(7): 1110-1116.
Check Digit Verification of cas no
The CAS Registry Mumber 1394076-92-6 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,3,9,4,0,7 and 6 respectively; the second part has 2 digits, 9 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 1394076-92:
(9*1)+(8*3)+(7*9)+(6*4)+(5*0)+(4*7)+(3*6)+(2*9)+(1*2)=186
186 % 10 = 6
So 1394076-92-6 is a valid CAS Registry Number.
1394076-92-6Relevant articles and documents
The design and identification of brain penetrant inhibitors of phosphoinositide 3-kinase α
Heffron, Timothy P.,Salphati, Laurent,Alicke, Bruno,Cheong, Jonathan,Dotson, Jennafer,Edgar, Kyle,Goldsmith, Richard,Gould, Stephen E.,Lee, Leslie B.,Lesnick, John D.,Lewis, Cristina,Ndubaku, Chudi,Nonomiya, Jim,Olivero, Alan G.,Pang, Jodie,Plise, Emile G.,Sideris, Steve,Trapp, Sean,Wallin, Jeffrey,Wang, Lan,Zhang, Xiaolin
, p. 8007 - 8020,14 (2020/09/15)
Inhibition of phosphoinositide 3-kinase (PI3K) signaling through PI3Kα has received significant attention for its potential in cancer therapy. While the PI3K pathway is a well-established and widely pursued target for the treatment of many cancer types due to the high frequency of abnormal PI3K signaling, glioblastoma multiforme (GBM) is particularly relevant because the pathway is implicated in more than 80% of GBM cases. Herein, we report the identification of PI3K inhibitors designed to cross the blood-brain barrier (BBB) to engage their target where GBM tumors reside. We leveraged our historical experience with PI3K inhibitors to identify correlations between physicochemical properties and transporter efflux as well as metabolic stability to focus the selection of molecules for further study.
