925705-73-3 Usage
Uses
TG 100713 is an inhibitor of PI3-kinase. TG 100713 inhibits endothelial cell proliferation.
Biological Activity
tg100713 is a pan-pi3k inhibitor against pi3kγ, pi3kδ, pi3kα and pi3kβ.pi3kγ and pi3kδ are a pair of pro-inflammatory pi3k isoforms that contribute to the inflammation that damages ischemia tissues upon reperfusion. phosphoinositide 3-kinases (pi3ks) are benefit to pro-cell survival roles during tissue iscg the reperfusion phhemia. therefore, it is possible that selectively inhibiting pro-inflammatory pi3k isoforms durinase could ultimately control overall tissue damage caused by ischemia/reperfusion injuries such as myocardial infarction.
in vitro
modeling studies suggested that the freedom of conformational rotation permitted by ring substituents controls isoform selectivity. although substituent ring of tg100-115, tg100713, and tg101110 all require energy minima at 30–40°, angles diverge of each compound results in paying differing penalties from this range. tg100-115 displays the greatest barrier to rotation and finally is the most isoform selective, tg100713 has the most conformational flexibility (ring a being almost freely rotatable with maxima ≈5 kcal; 1 kcal = 4.18 kj), suggesting the least selective, and tg101110 lies an intermediate position (several conformations ≦10 but some >>50 kcal) [1].
in vivo
the minimum structure which satisfies all three requirements is shown in tg100713, which so far has also displayed the best pi3k binding activity. interestingly, the sar profiles generating correlate quite well with the results of the initial in vivo screen further supports the involvement of pi3k as a target for inhibiting vascular permeability in related compounds [2].
IC 50
(pi3kγ, pi3kδ, pi3kα and pi3kβ): 50 nm, 24 nm, 165 nm and 215 nm
references
[1] doukas j, wrasidlo w, noronha g, dneprovskaia e, fine r, weis s, hood j, demaria a, soll r, cheresh d. phosphoinositide 3-kinase gamma/delta inhibition limits infarct size after myocardial ischemia/reperfusion injury. proc natl acad sci u s a. 2006 dec 26; 103(52):19866-71. [2] palanki ms, dneprovskaia e, doukas j, fine rm, hood j, kang x, lohse d, martin m, noronha g, soll rm, wrasidlo w, yee s, zhu h. discovery of 3,3'-(2,4-diaminopteridine-6,7-diyl)diphenol as an isozyme-selective inhibitor of pi3k for the treatment of ischemia reperfusion injury associated with myocardial infarction. j med chem. 2007 sep 6;50(18):4279-94. epub 2007 aug 9.
Check Digit Verification of cas no
The CAS Registry Mumber 925705-73-3 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 9,2,5,7,0 and 5 respectively; the second part has 2 digits, 7 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 925705-73:
(8*9)+(7*2)+(6*5)+(5*7)+(4*0)+(3*5)+(2*7)+(1*3)=183
183 % 10 = 3
So 925705-73-3 is a valid CAS Registry Number.
925705-73-3Relevant articles and documents
Discovery of 3,3′-(2,4-diaminopteridine-6,7-diyl)diphenol as an isozyme-selective inhibitor of PI3K for the treatment of ischemia reperfusion injury associated with myocardial infarction
Palanki, Moorthy S. S.,Dneprovskaia, Elena,Doukas, John,Fine, Richard M.,Hood, John,Kang, Xinshan,Lohse, Dan,Martin, Michael,Noronha, Glenn,Soll, Richard M.,Wrasidlo, Wolfgang,Yee, Shiyin,Zhu, Hong
, p. 4279 - 4294 (2008/02/13)
In studies aimed toward identifying effective and safe inhibitors of kinase signaling cascades that underlie ischemia/reperfusion (I/R) injury, we synthesized a series of pteridines and pyridopyrazines. The design strategy was inspired by the examination
Kinase inhibitors and methods of use thereof
-
Page/Page column 18, (2010/11/28)
Compositions and methods and are provided for treating disorders associated with compromised vasculostasis. Invention methods and compositions are useful for treating a variety of disorders including for example, stroke, myocardial infarction, cancer, isc
