Modifications of the GSK3β substrate sequence to produce substrate-mimetic inhibitors of Akt as potential anti-cancer therapeutics

Katherine J. Kayser; Matthew P. Glenn; Said M. Sebti; Jin Q. Cheng; Andrew D. Hamilton

doi:10.1016/j.bmcl.2007.01.004

Modifications of the GSK3β substrate sequence to produce substrate-mimetic inhibitors of Akt as potential anti-cancer therapeutics

Katherine J. Kayser, Matthew P. Glenn, Said M. Sebti, Jin Q. Cheng, Andrew D. Hamilton

Chemistry

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

Abstract

Amplification, overexpression, and elevated activation of Akt have been detected in many human malignancies making it an important target for cancer therapy. The Akt substrate-binding site offers a large number of potential interactions to an appropriately designed small molecule and can form the basis for the development of selective inhibitors. Here, we report the progression of GSK3β substrate-mimetic inhibitors towards the development of a potent, small molecule substrate-mimetic inhibitor of Akt.

Original language	English (US)
Pages (from-to)	2068-2073
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	17
Issue number	7
DOIs	https://doi.org/10.1016/j.bmcl.2007.01.004
State	Published - Apr 1 2007

Keywords

Akt
Cancer
Peptidomimetics
Protein kinase B
Substrate-mimetic

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2007.01.004

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title = "Modifications of the GSK3β substrate sequence to produce substrate-mimetic inhibitors of Akt as potential anti-cancer therapeutics",

abstract = "Amplification, overexpression, and elevated activation of Akt have been detected in many human malignancies making it an important target for cancer therapy. The Akt substrate-binding site offers a large number of potential interactions to an appropriately designed small molecule and can form the basis for the development of selective inhibitors. Here, we report the progression of GSK3β substrate-mimetic inhibitors towards the development of a potent, small molecule substrate-mimetic inhibitor of Akt.",

keywords = "Akt, Cancer, Peptidomimetics, Protein kinase B, Substrate-mimetic",

author = "Kayser, {Katherine J.} and Glenn, {Matthew P.} and Sebti, {Said M.} and Cheng, {Jin Q.} and Hamilton, {Andrew D.}",

note = "Funding Information: K.J.K. thanks Sanofi-Aventis for their funding of the American Chemical Society division of Medicinal Chemistry predoctoral fellowship. We also thank the National Institutes of Health (1R01 CA107078-01) for financial support of this work. ",

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doi = "10.1016/j.bmcl.2007.01.004",

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T1 - Modifications of the GSK3β substrate sequence to produce substrate-mimetic inhibitors of Akt as potential anti-cancer therapeutics

AU - Kayser, Katherine J.

AU - Glenn, Matthew P.

AU - Sebti, Said M.

AU - Cheng, Jin Q.

AU - Hamilton, Andrew D.

N1 - Funding Information: K.J.K. thanks Sanofi-Aventis for their funding of the American Chemical Society division of Medicinal Chemistry predoctoral fellowship. We also thank the National Institutes of Health (1R01 CA107078-01) for financial support of this work.

PY - 2007/4/1

Y1 - 2007/4/1

N2 - Amplification, overexpression, and elevated activation of Akt have been detected in many human malignancies making it an important target for cancer therapy. The Akt substrate-binding site offers a large number of potential interactions to an appropriately designed small molecule and can form the basis for the development of selective inhibitors. Here, we report the progression of GSK3β substrate-mimetic inhibitors towards the development of a potent, small molecule substrate-mimetic inhibitor of Akt.

AB - Amplification, overexpression, and elevated activation of Akt have been detected in many human malignancies making it an important target for cancer therapy. The Akt substrate-binding site offers a large number of potential interactions to an appropriately designed small molecule and can form the basis for the development of selective inhibitors. Here, we report the progression of GSK3β substrate-mimetic inhibitors towards the development of a potent, small molecule substrate-mimetic inhibitor of Akt.

KW - Akt

KW - Cancer

KW - Peptidomimetics

KW - Protein kinase B

KW - Substrate-mimetic

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Modifications of the GSK3β substrate sequence to produce substrate-mimetic inhibitors of Akt as potential anti-cancer therapeutics

Abstract

Keywords

ASJC Scopus subject areas

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