Virtual docking approaches to protein kinase B inhibition

Martino Forino; Dawoon Jung; John B. Easton; Peter J. Houghton; Maurizio Pellecchia

doi:10.1021/jm048962u

Virtual docking approaches to protein kinase B inhibition

Martino Forino, Dawoon Jung, John B. Easton, Peter J. Houghton, Maurizio Pellecchia

Research output: Contribution to journal › Article › peer-review

52 Scopus citations

Abstract

We examined some in silico approaches to identify Akt (protein kinase B) inhibitors. Experimental validation of selected compounds was achieved using a fluorescence-based enzymatic assay and a substrate phosphorylation assay involving the protein GSK-3. We report on success and failure obtained by using several strategies including FlexX, GOLD, and CSCORE, where the 100-200 top-scoring compounds from a 50000-compound library were experimentally tested. This study led to the identification of low micromolar Akt1 inhibitors.

Original language	English (US)
Pages (from-to)	2278-2281
Number of pages	4
Journal	Journal of Medicinal Chemistry
Volume	48
Issue number	7
DOIs	https://doi.org/10.1021/jm048962u
State	Published - Apr 7 2005
Externally published	Yes

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

Access to Document

10.1021/jm048962u

Fingerprint Dive into the research topics of 'Virtual docking approaches to protein kinase B inhibition'. Together they form a unique fingerprint.

Cite this

@article{a13ad2b16415449988c7bae2713050a8,

title = "Virtual docking approaches to protein kinase B inhibition",

abstract = "We examined some in silico approaches to identify Akt (protein kinase B) inhibitors. Experimental validation of selected compounds was achieved using a fluorescence-based enzymatic assay and a substrate phosphorylation assay involving the protein GSK-3. We report on success and failure obtained by using several strategies including FlexX, GOLD, and CSCORE, where the 100-200 top-scoring compounds from a 50000-compound library were experimentally tested. This study led to the identification of low micromolar Akt1 inhibitors.",

author = "Martino Forino and Dawoon Jung and Easton, {John B.} and Houghton, {Peter J.} and Maurizio Pellecchia",

year = "2005",

month = apr,

day = "7",

doi = "10.1021/jm048962u",

language = "English (US)",

volume = "48",

pages = "2278--2281",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

publisher = "American Chemical Society",

number = "7",

}

TY - JOUR

T1 - Virtual docking approaches to protein kinase B inhibition

AU - Forino, Martino

AU - Jung, Dawoon

AU - Easton, John B.

AU - Houghton, Peter J.

AU - Pellecchia, Maurizio

PY - 2005/4/7

Y1 - 2005/4/7

N2 - We examined some in silico approaches to identify Akt (protein kinase B) inhibitors. Experimental validation of selected compounds was achieved using a fluorescence-based enzymatic assay and a substrate phosphorylation assay involving the protein GSK-3. We report on success and failure obtained by using several strategies including FlexX, GOLD, and CSCORE, where the 100-200 top-scoring compounds from a 50000-compound library were experimentally tested. This study led to the identification of low micromolar Akt1 inhibitors.

AB - We examined some in silico approaches to identify Akt (protein kinase B) inhibitors. Experimental validation of selected compounds was achieved using a fluorescence-based enzymatic assay and a substrate phosphorylation assay involving the protein GSK-3. We report on success and failure obtained by using several strategies including FlexX, GOLD, and CSCORE, where the 100-200 top-scoring compounds from a 50000-compound library were experimentally tested. This study led to the identification of low micromolar Akt1 inhibitors.

UR - http://www.scopus.com/inward/record.url?scp=17144416825&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=17144416825&partnerID=8YFLogxK

U2 - 10.1021/jm048962u

DO - 10.1021/jm048962u

M3 - Article

C2 - 15801821

AN - SCOPUS:17144416825

VL - 48

SP - 2278

EP - 2281

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 7

ER -