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Overview
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Background
TG100-115 is an inhibitor of PI3Kγ and PI3Kδ with IC50 values of 83 nM and 235 nM, respectively. TG100-115 shows no obvious activity against PI3Kα and PI3Kβ [1].TG100-115 remarkably reduced eosinophil accumulation, BALF levels of classic Th2 cytokine IL-13, perivascular and peribronchial leukocyte accumulations, and bronchiolar mucin accumulation in a murine model. Besides, TG100-115 showed to reduce airway hyper-responsiveness (AHR) by approximately 50% in asthmatic mice. Moreover, TG100-115 has been reported to reduce both smoke-and LPS-induced neutrophil and LPS-induced classic Th1 cytokine TNFα accumulations in mice [2].
[1] Doukas J1, Wrasidlo W, Noronha G, Dneprovskaia E, Fine R, Weis S, Hood J, Demaria A, Soll R, Cheresh D. hosphoinositide 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] Doukas J1, Eide L, Stebbins K, Racanelli-Layton A, Dellamary L, Martin M, Dneprovskaia E, Noronha G, Soll R, Wrasidlo W, Acevedo LM, Cheresh DA. Aerosolized phosphoinositide 3-kinase gamma/delta inhibitor TG100-115 [3-[2,4-diamino-6-(3-hydroxyphenyl)pteridin-7-yl]phenol] as a therapeutic candidate for asthma and chronic obstructive pulmonary disease. J Pharmacol Exp Ther. 2009 Mar;328(3):758-65.
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