Pim 1 kinase inhibitor ETP-45299 suppresses cellular proliferation and synergizes with PI3K inhibition

被引：48

作者：

Blanco-Aparicio, Carmen ^{[1
]}

Garcia Collazo, Ana Maria ^{[1
]}

Oyarzabal, Julen ^{[1
]}

Leal, Juan F. ^{[1
]}

Isabel Albaran, Maria ^{[1
]}

Ramos Lima, Francisco ^{[1
]}

Pequeno, Belen ^{[1
]}

Ajenjo, Nuria ^{[1
]}

Becerra, Mercedes ^{[1
]}

Alfonso, Patricia ^{[1
]}

Isabel Reymundo, Maria ^{[1
]}

Palacios, Irene ^{[1
]}

Mateos, Genoveva ^{[1
]}

Quinones, Helena ^{[1
]}

Corrioneio, Ana ^{[1
]}

Carnero, Amancio ^{[1
]}

Pevarello, Paolo ^{[1
]}

Rodriguez Lopez, Ana ^{[1
]}

Fominaya, Jesus ^{[1
]}

Pastor, Joaquin ^{[1
]}

Bischoff, James R. ^{[1
]}

机构：

[1] Spanish Natl Canc Res Ctr CNIO, Expt Therapeut Programme, Madrid 28029, Spain

来源：

CANCER LETTERS | 2011年 / 300卷 / 02期

关键词：

Pim; 1; Kinase inhibitors; PI3K; AML; PUTATIVE ONCOGENE PIM-1; SERINE/THREONINE KINASES; STRUCTURAL BASIS; C-MYC; LEUKEMIA; PROTEIN; GROWTH; CANCER; PHOSPHORYLATION; ACTIVATION;

D O I：

10.1016/j.canlet.2010.09.016

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

The serine/threonine Pim 1 kinase is an oncogene whose expression is deregulated in several human cancers Overexpression of Pim 1 facilitates cell cycle progression and suppresses apoptosis Hence pharmacologic inhibitors of Pim 1 are of therapeutic interest for cancer ETP-45299 is a potent and selective inhibitor of Pun 1 that inhibits the phosphorylation of Bad and 4EBP1 in cells and suppresses the proliferation of several non-solid and solid human tumor cell lines The combination of the PI3K inhibitor GDC-0941 with ETP-45299 was strongly synergistic in MV-4-11 AML cells indicating that the combination of selective Pim kinase inhibitors and PI3K inhibitor could have clinical benefit (C) 2010 Elsevier Ireland Ltd All rights reserved

引用

页码：145 / 153

页数：9

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