Chemical Properties
Pale Yellow Solid
Uses
Allosteric Akt (PKB) inhibitors used in synergistic combination therapy for the treatment of cancer
Definition
ChEBI: 3-[1-[[4-(7-phenyl-3H-imidazo[4,5-g]quinoxalin-6-yl)phenyl]methyl]-4-piperidinyl]-1H-benzimidazol-2-one is a member of piperidines.
Biological Activity
akt inhibitor viii is a cell-permeable, reversible and potent, selective inhibitor of akt1, akt2 and akt3 with ic50 values of 58 nm, 210 nm and 2.12 μm, respectively.akt inhibitor viii has shown to remarkably increase anti-proliferation induced by furanodiene in human breast cancer cell mcf-7. akt inhibitor viii could enhance the furanodiene- stimulated akt and p-akt expression decreases as well as increase furanodiene-induced parp cleavage in mcf-7 cells [1].akt inhibitor viii has been revealed to inhibit igf-1-induced akt phosphorylation in a concentration-dependent manner. akt inhibitor viii has also been demonstrated to reduce pras40 phosphorylation in pc12 cells [2].
Enzyme inhibitor
This dual Akt1/Akt2 inhibitor (FW = 551.64 g/mol; CAS 612847-09-3; Soluble to 20 mM in DMSO with gentle warming), also named 1,3- dihydro-1-[1-[[4-(6-phenyl-1H-imidazo[4,5-g]quinoxalin-7-yl)phenyl]- methyl]-4-piperidinyl]-2H-benzimidazol-2-one, targets Protein kinase B (PKB) isoforms Akt1 (IC50 = 50 nM) and Akt2 (IC50 = 210 nM), serine/threonine-specific protein kinases that play a key role in multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription and cell migration. Akti-1/2 is selective for Akt1 and 2 over a panel of other tyrosine and serine/threonine kinases. It also sensitizes LnCaP cells to TRAIL (TNF-related apoptosis-inducing ligand) induced apoptosis. Complete inhibition is achieved in liver cells treated with 1-10 μM. Akti-1/2 also blocks insulin regulation of PEP carboxykinase and glucose 6-phosphatase expression.
References
[1] zhong z1, dang y, yuan x, guo w, li y, tan w, cui j, lu j, zhang q, chen x, wang y. furanodiene, a natural product, inhibits breast cancer growth both in vitro and in vivo. cell physiol biochem. 2012;30(3):778-90.
[2] wang h1, zhang q, zhang l, little pj, xie x, meng q, ren y, zhou l, gao g, quirion r, zheng w. insulin-like growth factor-1 induces the phosphorylation of pras40 via the pi3k/akt signaling pathway in pc12 cells. neurosci lett. 2012 may 10;516(1):105-9.
