Uses
TGX-221 is a potent, selective, and cell permeable inhibitor of Phosphatidylinositol 3-kinase (PI3K) p110β.
Definition
ChEBI:9-(1-anilinoethyl)-7-methyl-2-(4-morpholinyl)-4-pyrido[1,2-a]pyrimidinone is a pyridopyrimidine.
General Description
A cell-permeable morpholino-pyrimidinone compound that acts as a reversible, ATP-competitive, selective, and highly potent inhibitor of PI 3-Kβ (IC50 = 0.005, 0.1, 5, and ≥3.5 μM for -β, -δ, -α and -γ isoforms, respectively) with little activity against a panel of 15 commonly studied protein kinases even at concentrations as high as 10.0 μM. An excellent tool for studying p110β-dependent responses both in cells in vitro and in animals in vivo.
Biological Activity
tgx-221 is a potent inhibitor of (phosphatidylinositol 3-kinases) pi3k which specifically inhibits pi3k -p110β isoform with ic50 value of 8.5 nm [1].in j774.2 macrophage cells, tgx-221 has been demonstrated to reduce insulin-induced phosphorylation of ser473 of protein kinase b (pkb). while in in cho-ir and 3t3-l1 cells, tgx-221 has no effect on pkb phosphprylation [1].
Biochem/physiol Actions
Cell permeable: yes
in vivo
tgx-221 significantly improved blood flow in fecl3-induced arterial thrombosis as well as increased tail and renal bleeding times in mice. in addition, tgx-221 has revealed to disrupt cfrs in a folts model of arterial thrombosis in male sprague-dawley rats [2].
References
[1] chaussade c1, rewcastle gw, kendall jd, denny wa, cho k, gr nning lm, chong ml, anagnostou sh,jackson sp, daniele n, shepherd pr. evidence for functional redundancy of class ia pi3k isoforms in insulin signalling. biochem j. 2007 jun 15;404(3):449-58.
[2] bird je1, smith pl, bostwick js, shipkova p, schumacher wa. bleeding response induced by anti-thrombotic doses of a phosphoinositide 3-kinase (pi3k)-β inhibitor in mice. thromb res. 2011 jun;127(6):560-4.
