MS-1020 is a novel small molecule that selectively inhibits JAK3 activity

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Title
MS-1020 is a novel small molecule that selectively inhibits JAK3 activity
Author(s)
B H Kim; Sei Ryang Oh; C H Yin; Sangku Lee; Eun Ah Kim; M S Kim; C Sandoval; S Jayabose; E A Bach; Hyeong Kyu Lee; G H Baeg
Bibliographic Citation
British Journal of Haematology, vol. 148, no. 1, pp. 132-143
Publication Year
2010
Abstract
In order to identify Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling inhibitors, a cell-based high throughput screening was performed using a plant extract library that identified Nb-(α-hydroxynaphthoyl)serotonin called MS-1020 as a novel JAK3 inhibitor. MS-1020 potently inhibited persistently-active STAT3 in a cell type-specific manner. Further examination showed that MS-1020 selectively blocked constitutively-active JAK3 and consistently suppressed interleukin-2-induced JAK3/STAT5 signalling but not prolactin-induced JAK2/STAT5 signalling. Furthermore, MS-1020 affected cell viability only in cancer cells harbouring persistently-active JAK3/STATs, and in vitro kinase assays showed MS-1020 binds directly with JAK3, blocking its catalytic activity. Therefore, the present study suggested that this reagent selectively inhibits JAK3 and subsequently leads to a block in STAT signalling. Finally, MS-1020 decreased cell survival by inducing apoptosis via down-regulation of anti-apoptotic gene expression. These results suggest that MS-1020 may have therapeutic potential in the treatment of cancers harbouring aberrant JAK3 signalling.
Keyword
CancerCell-based high throughput screeningJanus kinase/signal transducer and activator of transcriptionPlant extractsSmall molecule inhibitor
ISSN
0007-1048
Publisher
Wiley
DOI
http://dx.doi.org/10.1111/j.1365-2141.2009.07925.x
Type
Article
Appears in Collections:
Ochang Branch Institute > 1. Journal Articles
Ochang Branch Institute > Chemical Biology Research Center > 1. Journal Articles
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