dc.contributor.author |
Singh, Kurnvir |
|
dc.contributor.author |
Tanui, Rose |
|
dc.contributor.author |
Gameiro, Armanda |
|
dc.contributor.author |
Eisenberg, Gilad |
|
dc.contributor.author |
Colas, Claire |
|
dc.contributor.author |
Schlessinger, Avner |
|
dc.contributor.author |
Grewer, Christof |
|
dc.date.accessioned |
2019-02-12T09:18:11Z |
|
dc.date.available |
2019-02-12T09:18:11Z |
|
dc.date.issued |
2016-12-24 |
|
dc.identifier.citation |
http://dx.doi.org/10.1016/j.bmcl.2016.12.063 |
en_US |
dc.identifier.uri |
http://41.89.227.156:8080/xmlui/handle/123456789/828 |
|
dc.description.abstract |
The glutamine transporter ASCT2 has been identified as a promising target to inhibit rapid growth of cancer
cells. However, ASCT2 pharmacology is not well established. In this report, we performed a systematic
structure activity analysis of a series of substituted benzylproline derivatives. Substitutions on the phenyl
ring resulted in compounds with characteristics of ASCT2 inhibitors. Apparent binding affinity increased
with increasing hydrophobicity of the side chain. In contrast, interaction of the ASCT2 binding site with
specific positions on the phenyl ring was not observed. The most potent compound inhibits the ASCT2
anion conductance with a Ki of 3 lM, which is in the same range as that of more bulky and higher molecular
weight inhibitors recently reported by others. The experimental results are consistent with computational
analysis based on docking of the inhibitors against an ASCT2 homology model. The benzylproline
scaffold provides a valuable tool for further improving binding potency of future ASCT2 inhibitors. |
en_US |
dc.language.iso |
en |
en_US |
dc.publisher |
Bioorganic & Medicinal Chemistry Letters |
en_US |
dc.subject |
Neutral amino acid transporter ASCT2 Inhibitors Glutamine transport Kinetics Patch clamp Pharmacology |
en_US |
dc.title |
Structure activity relationships of benzylproline-derived inhibitors of the glutamine transporter ASCT2 |
en_US |
dc.type |
Article |
en_US |