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 -
