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Discovery and biological activity of computer-assisted drug designed Akt pathway inhibitors.

Abstract：

:The P13K/Akt pathway is a growth-regulating cellular signaling pathway that is over-activated in numerous human cancers. A novel series of Akt pathway inhibitors were identified using iterative pharmacophore modeling, energy-based calculations, and property predictions of known Akt inhibitors. Inhibitory effects on activation of Akt and growth of human neoplastic cells are reported. Results show variable inhibitory effects of three selected compounds on Akt phosphorylation at a key activation site, and on proliferation of tumorigenic cells. We identify one lead compound with potent inhibitory activity on both human carcinoma cell proliferation and Akt activation.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Uko NE,Güner OF,Barnett LMA,Matesic DF,Bowen JP

doi

10.1016/j.bmcl.2018.08.006

subject

Has Abstract

pub_date

2018-10-15 00:00:00

pages

3247-3250

issue

19

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(18)30669-3

journal_volume

28

pub_type

杂志文章

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