Kinase inhibitory potencies and in vitro antiproliferative activities of N-10 substituted pyrrolo[2,3-a]carbazole derivatives

Akué‐Gédu, Rufine; Letribot, Boris; Saugues, Emmanuelle; Débiton, Eric; Anizon, Fabrice; Moreau, Pascale

doi:10.1016/j.bmcl.2012.03.098

Cited by 30 publications

(15 citation statements)

References 13 publications

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“…Moreover, the triple knockout Pim kinase mice are viable and fertile, which suggests that inhibition of the Pim kinase family could be possible without severe side effects (Mikkers et al, 2004). By now, several independent groups have developed small-molecule inhibitors against Pim kinases (Akue-Gedu et al, 2012;Gavara et al, 2013). Stemonamide synthetic intermediates derivative can inhibit Pim-3 as well as Pim-1 and Pim-2 activities and can reduce tumor growth in vivo xenograft models using a human pancreatic cancer cell line without causing major adverse effects (Li et al, 2010;Wang et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Aberrant Expression of Pim-3 Promotes Proliferation and Migration of Ovarian Cancer Cells

Zhuang¹,

Zhao²,

Hei³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Pim kinase-3(Pim-3), a member of serine/threonine protein kinases, has been implicated in multiple human cancers and involved in Myc-induced tumorigenesis. However, little is known regarding its expression and biological function in human ovarian cancer. In this study we showed that the clinical significance and biological functions of Pim-3 in ovarian cancer and found that higher Pim-3 mRNA level are detected in ovarian cancer tissues than those in normal ovarian tissues. There are significant correlations between higher Pim-3 expression levels with the FIGO stage, histopathological subtypes, and distant metastasis in ovarian cancer patients. Lentivirus-mediated gene overexpression of Pim-3 significantly promotes the proliferation and migration of SKOV3 cell lines. Furthermore, MACC1 and Pim-3 expression were significantly correlated in human ovarian cancer cells, and overexpression of Pim-3 in ovary cancer cells increased MACC1 mRNA and protein expression. The data indicate that Pim-3 acts as a putative oncogene in ovary cancer and could be a viable diagnostic and therapeutic target for ovarian cancer.

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Section: Discussionmentioning

confidence: 99%

Aberrant Expression of Pim-3 Promotes Proliferation and Migration of Ovarian Cancer Cells

Zhuang¹,

Zhao²,

Hei³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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show abstract

“…Several independent groups developed small-molecule inhibitors against Pim kinases, including flavonol quercetargetin, imidazole [ (53,54). Among them, 1,6-dihydropyrazolo [4,3-c]carbazoles, 3,6-dihydropyrazolo [3,4-c]carbazoles, and pyrrolo[2,3-g]indazoles could be used as an interesting molecular tool to study Pim-3 biological functions (52).…”

Section: Discussionmentioning

confidence: 99%

A Novel Regulatory Mechanism of Pim-3 Kinase Stability and Its Involvement in Pancreatic Cancer Progression

Zhang

Liu

Wang

et al. 2013

Molecular Cancer Research

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Translationally controlled tumor protein (TCTP/TPT1) was identified from a yeast 2-hybrid screen and shown to interact with Pim-3, a member of the proto-oncogene Pim family with serine/threonine kinase activity. TCTP was aberrantly expressed in human pancreatic cancer cells and malignant ductal epithelial cells, but not in normal pancreatic duct epithelial cells adjacent to tumor foci of human pancreatic cancer tissue. Moreover, TCTP colocalized with Pim-3 both in human pancreatic cancer cells and in clinical tissues. Mapping studies revealed that the interaction between Pim-3 and TCTP occurred through the C-terminal region of Pim-3 and N-terminal region of TCTP. Although Pim-3 had no effect on TCTP expression or phosphorylation, overexpression of TCTP increased the amount of Pim-3 in a dose-dependent manner. Interestingly, RNAi-mediated ablation of TCTP expression reduced Pim-3 protein but not mRNA, through a mechanism involving the ubiquitin-proteasome degradation system. As a consequence of Pim-3 instability and subsequent degradation, tumor growth in vitro and in vivo was inhibited by arresting cell-cycle progression and enhancing apoptosis. Furthermore, TCTP and Pim-3 expression were significantly correlated in pancreatic adenocarcinoma specimens, and patients with highly expressed TCTP and Pim-3 presented with a more advanced tumor stage. These observations indicate that TCTP enhances Pim-3 stability to simultaneously promote and prevent cell-cycle progression and apoptosis, respectively. Hence, TCTP and Pim-3 serve a pivotal role in human pancreatic cancer with important ramifications for clinical diagnostic and therapeutic implications.

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“…51 This compound showed antiproliferative activity in the low micromolar range against various cell lines and inhibited the phosphorylation of 4E-BP1 in MV-4-11 cells. Compound 12, which was discovered independently by another research group, 52 shared some structural similarity with 11 by also bearing an indole ring. However, no cellular activity of the latter molecule was revealed.…”

Section: ■ Inhibitors Of the Pim Kinasesmentioning

confidence: 98%

Potential Use of Selective and Nonselective Pim Kinase Inhibitors for Cancer Therapy

Drygin¹,

Haddach²,

Pierre³

et al. 2012

J. Med. Chem.

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Kinase inhibitory potencies and in vitro antiproliferative activities of N-10 substituted pyrrolo[2,3-a]carbazole derivatives

Cited by 30 publications

References 13 publications

Aberrant Expression of Pim-3 Promotes Proliferation and Migration of Ovarian Cancer Cells

Aberrant Expression of Pim-3 Promotes Proliferation and Migration of Ovarian Cancer Cells

A Novel Regulatory Mechanism of Pim-3 Kinase Stability and Its Involvement in Pancreatic Cancer Progression

Potential Use of Selective and Nonselective Pim Kinase Inhibitors for Cancer Therapy

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