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Inhibition of cRAF

PubChem AID
415640
Primary Citation
From a natural product lead to the identification of potent and selective benzofuran-3-yl-(indol-3-yl)maleimides as glycogen synthase kinase 3beta inhibitors that suppress proliferation and survival of pancreatic cancer cells [PMID: 19338355]
Source
External ID
BioAssay Type
Confirmatory
Tested Substances
Tested Compounds
Version
Status
Live
Dates
  • Deposit:
    2010-05-26
  • Modify:
    2018-09-10
Description
This bioassay record (AID 415640) reports results from the above primary citation. Additional data from the same publication are reported in a total of 37 BioAssay records in PubChem.

1 Description

Title: From a natural product lead to the identification of potent and selective benzofuran-3-yl-(indol-3-yl)maleimides as glycogen synthase kinase 3beta inhibitors that suppress proliferation and survival of pancreatic cancer cells.

Abstract: Recent studies have demonstrated that glycogen synthase kinase 3beta (GSK-3beta) is overexpressed in human colon and pancreatic carcinomas, contributing to cancer cell proliferation and survival. Here, we report the design, synthesis, and biological evaluation of benzofuran-3-yl-(indol-3-yl)maleimides, potent GSK-3beta inhibitors. Some of these compounds show picomolar inhibitory activity toward GSK-3beta and an enhanced selectivity against cyclin-dependent kinase 2 (CDK-2). Selected GSK-3beta inhibitors were tested in the pancreatic cancer cell lines MiaPaCa-2, BXPC-3, and HupT3. We determined that some of these compounds, namely compounds 5, 6, 11, 20, and 26, demonstrate antiproliferative activity against some or all of the pancreatic cancer cells at low micromolar to nanomolar concentrations. We found that the treatment of pancreatic cancer cells with GSK-3beta inhibitors 5 and 26 resulted in suppression of GSK-3beta activity and a distinct decrease of the X-linked inhibitor of apoptosis (XIAP) expression, leading to significant apoptosis. The present data suggest a possible role for GSK-3beta inhibitors in cancer therapy, in addition to their more prominent applications in CNS disorders.

2 Comment

Journal: J Med Chem

Year: 2009

Volume: 52

Issue: 7

First Page: 1853

Last Page: 1863

DOI: 10.1021/jm801317h

Target ChEMBL ID: CHEMBL1906

ChEMBL Target Name: Serine/threonine-protein kinase RAF

ChEMBL Target Type: SINGLE PROTEIN - Target is a single protein chain

Relationship Type: H - Homologous protein target assigned

Confidence: Homologous single protein target assigned

3 Result Definitions

4 Data Table

5 Target

8 Identity

8.1 BioAssay Name

Inhibition of cRAF

8.2 Source

8.3 External ID

8.4 Project Category

Literature, Extracted

8.5 BioAssay Type

Confirmatory

8.6 Deposit Date

2010-05-26

8.7 Modify Date

Version 1.1
Version 2.1
Version 2.2
Version 2.3
Version 2.4
Version 2.5
Version 3.1
Version 3.2
Version 4.1
Version 4.2
Version 4.3
Version 4.4
Version 4.5
Version 4.6
Version 4.7
Version 5.1
2018-09-10 (currently shown)

8.8 Status

Live

9 Same-Publication BioAssays

10 BioAssay Annotations

Assay Type
Binding

11 Information Sources

  1. PubChem
  2. ChEMBL
    LICENSE
    Access to the web interface of ChEMBL is made under the EBI's Terms of Use (http://www.ebi.ac.uk/Information/termsofuse.html). The ChEMBL data is made available on a Creative Commons Attribution-Share Alike 3.0 Unported License (http://creativecommons.org/licenses/by-sa/3.0/).
    http://www.ebi.ac.uk/Information/termsofuse.html
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