DICHLORO(2Z)-2-[(4-OXO-4H-1-BENZOPYRAN-3-YL)METHYLENE]HYDRAZINECARBOTHIOAMIDE COPPER COMPLEX

Description

The kinase Akt (also known as protein kinase B or PKB) modulates cell proliferation, metabolism, and survival, as well as angiogenesis. Akt inhibitor XI is a cell-permeable, copper-containing 3-formylchromone derivative that inhibits Akt in an array of cancer cells (IC₅₀s = 10-34 μM). It also causes NF-κB inactivation in an orthotopic pancreatic tumor model using COLO 357 cells. Molecular modeling indicates that this inhibitor interacts with the pleckstrin homology and kinase domains of Akt. Akt inhibitor XI is commonly used in the range of 1-20 μM to assess the role of Akt in cellular responses.

Uses

Akt inhibitor XI inhibits Akt in various cancer cells. Protein kinase B (PKB or Akt) is aserene/threonine kinase, which is involved in a wide variety of cellular processes including metabolism, apoptosis and cell proliferation. Furthermore,Akt inhibitor XIwas employed in a biological study that aimed to develop a novel coiled-coil three-hybrid system that can identify potential allosteric inhibitors.

Biological Activity

Akt/PKB inhibitor (IC 50 = 100 nM) that interacts with the PH and kinase domains. Inhibits cell proliferation in various cancer cell lines in vitro and decreases NF- κ B activity and tumor load in vivo .

in vivo

storage

Store at +4°C

References

[1] BRENDAN D MANNING L C C. AKT/PKB signaling: navigating downstream.[J]. Cell, 2007, 129 7: 1261-1274. DOI: 10.1016/j.cell.2007.06.009
[2] T L YUAN  L C C. PI3K pathway alterations in cancer: variations on a theme[J]. Oncogene, 2008, 27 41: 5497-5510. DOI: 10.1038/onc.2008.245
[3] VIVEK BARVE. Synthesis, Molecular Characterization, and Biological Activity of Novel Synthetic Derivatives of Chromen-4-one in Human Cancer Cells[J]. Journal of Medicinal Chemistry, 2006, 49 13: 3800-3808. DOI: 10.1021/jm051068y
[4] GABRIEL FRAMPTON. Interleukin-6-driven progranulin expression increases cholangiocarcinoma growth by an Akt-dependent mechanism.[J]. Gut, 2012, 61 2: 268-277. DOI: 10.1136/gutjnl-2011-300643
[5] MARK S RYBCHYN. An Akt-dependent increase in canonical Wnt signaling and a decrease in sclerostin protein levels are involved in strontium ranelate-induced osteogenic effects in human osteoblasts.[J]. The Journal of Biological Chemistry, 2011: 23771-23779. DOI: 10.1074/jbc.m111.251116
[6] N ZAREEN  L A G  S C Biswas. A feed-forward loop involving Trib3, Akt and FoxO mediates death of NGF-deprived neurons[J]. Cell Death and Differentiation, 2013, 20 12: 1719-1730. DOI: 10.1038/cdd.2013.128