In:
ChemMedChem, Wiley, Vol. 10, No. 12 ( 2015-12), p. 1980-1987
Abstract:
Slingshot proteins form a small group of dual‐specific phosphatases that modulate cytoskeleton dynamics through dephosphorylation of cofilin and Lim kinases (LIMK). Small chemical compounds with Slingshot‐inhibiting activities have therapeutic potential against cancers or infectious diseases. However, only a few Slingshot inhibitors have been investigated and reported, and their cellular activities have not been examined. In this study, we identified two rhodanine‐scaffold‐based para ‐substituted benzoic acid derivatives as competitive Slingshot inhibitors. The top compound, ( Z )‐4‐((4‐((4‐oxo‐2‐thioxo‐3‐( o ‐tolyl)thiazolidin‐5‐ylidene)methyl)phenoxy)methyl)benzoic acid ( D3 ) had an inhibition constant ( K i ) of around 4 μ m and displayed selectivity over a panel of other phosphatases. Moreover, compound D3 inhibited cell migration and cofilin dephosphorylation after nerve growth factor (NGF) or angiotensin II stimulation. Therefore, our newly identified Slingshot inhibitors provide a starting point for developing Slingshot‐targeted therapies.
Type of Medium:
Online Resource
ISSN:
1860-7179
,
1860-7187
DOI:
10.1002/cmdc.201500454
Language:
English
Publisher:
Wiley
Publication Date:
2015
detail.hit.zdb_id:
2209649-8
SSG:
15,3
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