New thiazole carboxamides as potent inhibitors of Akt kinases

Shaohua Chang; Zhang Zhang; Xiaoxi Zhuang; Jinfeng Luo; Xianwen Cao; Honglin Li; Zhengchao Tu; Xiaoyun Lu; Xiaomei Ren; Ke Ding

doi:10.1016/j.bmcl.2011.11.080

New thiazole carboxamides as potent inhibitors of Akt kinases

Shaohua Chang
, Zhang Zhang
, Xiaoxi Zhuang
, Jinfeng Luo
, Xianwen Cao
, Honglin Li
, Zhengchao Tu
, Xiaoyun Lu
, Xiaomei Ren
, Ke Ding^*

^*Corresponding author for this work

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

38 Scopus citations

Abstract

A new series of 2-substituted thiazole carboxamides were identified as potent pan inhibitors against all three isoforms of Akt (Akt1, Akt2 and Akt3) by systematic optimization of weak screening hit N-(1-amino-3-phenylpropan-2-yl)- 2-phenylthiazole-5-carboxamide (1). One of the most potent compounds, 5m, inhibited the kinase activities of Akt1, Akt2 and Akt3 with IC ₅₀ values of 25, 196 and 24 nM, respectively. The compound also potently inhibited the phosphorylation of downstream MDM2 and GSK3β proteins, and displayed strongly antiproliferative activity in prostate cancer cells. The inhibitors might serve as lead compounds for further development of novel effective anticancer agents.

Original language	English
Pages (from-to)	1208-1212
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	22
Issue number	2
DOIs	https://doi.org/10.1016/j.bmcl.2011.11.080
State	Published - 15 Jan 2012
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Akt kinase
Inhibitors
Thiazole carboxamides

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10.1016/j.bmcl.2011.11.080

Cite this

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title = "New thiazole carboxamides as potent inhibitors of Akt kinases",

abstract = "A new series of 2-substituted thiazole carboxamides were identified as potent pan inhibitors against all three isoforms of Akt (Akt1, Akt2 and Akt3) by systematic optimization of weak screening hit N-(1-amino-3-phenylpropan-2-yl)- 2-phenylthiazole-5-carboxamide (1). One of the most potent compounds, 5m, inhibited the kinase activities of Akt1, Akt2 and Akt3 with IC 50 values of 25, 196 and 24 nM, respectively. The compound also potently inhibited the phosphorylation of downstream MDM2 and GSK3β proteins, and displayed strongly antiproliferative activity in prostate cancer cells. The inhibitors might serve as lead compounds for further development of novel effective anticancer agents.",

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author = "Shaohua Chang and Zhang Zhang and Xiaoxi Zhuang and Jinfeng Luo and Xianwen Cao and Honglin Li and Zhengchao Tu and Xiaoyun Lu and Xiaomei Ren and Ke Ding",

year = "2012",

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day = "15",

doi = "10.1016/j.bmcl.2011.11.080",

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}

TY - JOUR

T1 - New thiazole carboxamides as potent inhibitors of Akt kinases

AU - Chang, Shaohua

AU - Zhang, Zhang

AU - Zhuang, Xiaoxi

AU - Luo, Jinfeng

AU - Cao, Xianwen

AU - Li, Honglin

AU - Tu, Zhengchao

AU - Lu, Xiaoyun

AU - Ren, Xiaomei

AU - Ding, Ke

PY - 2012/1/15

Y1 - 2012/1/15

N2 - A new series of 2-substituted thiazole carboxamides were identified as potent pan inhibitors against all three isoforms of Akt (Akt1, Akt2 and Akt3) by systematic optimization of weak screening hit N-(1-amino-3-phenylpropan-2-yl)- 2-phenylthiazole-5-carboxamide (1). One of the most potent compounds, 5m, inhibited the kinase activities of Akt1, Akt2 and Akt3 with IC 50 values of 25, 196 and 24 nM, respectively. The compound also potently inhibited the phosphorylation of downstream MDM2 and GSK3β proteins, and displayed strongly antiproliferative activity in prostate cancer cells. The inhibitors might serve as lead compounds for further development of novel effective anticancer agents.

AB - A new series of 2-substituted thiazole carboxamides were identified as potent pan inhibitors against all three isoforms of Akt (Akt1, Akt2 and Akt3) by systematic optimization of weak screening hit N-(1-amino-3-phenylpropan-2-yl)- 2-phenylthiazole-5-carboxamide (1). One of the most potent compounds, 5m, inhibited the kinase activities of Akt1, Akt2 and Akt3 with IC 50 values of 25, 196 and 24 nM, respectively. The compound also potently inhibited the phosphorylation of downstream MDM2 and GSK3β proteins, and displayed strongly antiproliferative activity in prostate cancer cells. The inhibitors might serve as lead compounds for further development of novel effective anticancer agents.

KW - Akt kinase

KW - Inhibitors

KW - Thiazole carboxamides

UR - https://www.scopus.com/pages/publications/84855699631

U2 - 10.1016/j.bmcl.2011.11.080

DO - 10.1016/j.bmcl.2011.11.080

M3 - 文章

C2 - 22172705

AN - SCOPUS:84855699631

SN - 0960-894X

VL - 22

SP - 1208

EP - 1212

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 2

ER -

New thiazole carboxamides as potent inhibitors of Akt kinases

Abstract

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Keywords

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