Type

Journal Article

Authors

Breandán Kennedy
William M. Gallagher
Alison Reynolds
Emer Conroy
David Fennelly
Clare T. Butler
Diarmuid O'Donoghue
Aoife Maguire
Kieran Sheahan
Rory Casey
and 3 others

Subjects

Biochemistry

Topics
colorectal cancer cell survival il 6 colorectal cancer crc il 1 quininib cell migration drug resistance novel the small molecule inhibitors molecular weight

Preclinical validation of the small molecule drug quininib as a novel therapeutic for colorectal cancer (2016)

Abstract Colorectal cancer (CRC) is a leading cause of cancer deaths. Molecularly targeted therapies (e.g. bevacizumab) have improved survival rates but drug resistance ultimately develops and newer therapies are required. We identified quininib as a small molecule drug with anti-angiogenic activity using in vitro, ex vivo and in vivo screening models. Quininib (2-[(E)-2-(Quinolin-2-yl) vinyl] phenol), is a small molecule drug (molecular weight 283.75?g/mol), which significantly inhibited blood vessel development in zebrafish embryos (p?<?0.001). In vitro, quininib reduced endothelial tubule formation (p?<?0.001), cell migration was unaffected by quininib and cell survival was reduced by quininib (p?<?0.001). Using ex vivo human CRC explants, quininib significantly reduced the secretions of IL-6, IL-8, VEGF, ENA-78, GRO-?, TNF, IL-1? and MCP-1 ex vivo (all values p?<?0.01). Quininib is well tolerated in mice when administered at 50?mg/kg intraperitoneally every 3 days and significantly reduced tumour growth of HT-29-luc2 CRC tumour xenografts compared to vehicle control. In addition, quininib reduced the signal from a ?v?3 integrin fluorescence probe in tumours 10 days after treatment initiation, indicative of angiogenic inhibition. Furthermore, quininib reduced the expression of angiogenic genes in xenografted tumours. Collectively, these findings support further development of quininib as a novel therapeutic agent for CRC.
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Full list of authors on original publication

Breandán Kennedy, William M. Gallagher, Alison Reynolds, Emer Conroy, David Fennelly, Clare T. Butler, Diarmuid O'Donoghue, Aoife Maguire, Kieran Sheahan, Rory Casey and 3 others

Experts in our system

1
Breandán N Kennedy
University College Dublin
Total Publications: 55
 
2
William M Gallagher
University College Dublin
Total Publications: 148
 
3
Alison Reynolds
University College Dublin
Total Publications: 20
 
4
Emer Conroy
Royal College of Surgeons in Ireland
Total Publications: 8
 
5
David Fennelly
Trinity College Dublin
Total Publications: 11
 
6
Clare T Butler
University College Dublin
Total Publications: 6
 
7
Diarmuid O'Donoghue
University College Dublin
Total Publications: 42
 
8
Aoife Maguire
Trinity College Dublin
Total Publications: 5
 
9
Kieran Sheahan
University College Dublin
Total Publications: 40
 
10
Rory Casey
Trinity College Dublin
Total Publications: 4