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Title 

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

Authors 

B H KimSei Ryang OhC H YinSangku LeeEun Ah KimM S KimC SandovalS JayaboseE A BachHyeong Kyu LeeG H Baeg

Publisher 

Wiley-Blackwell

Issue Date 

2010

Citation 

British Journal of Haematology, vol. 148, no. 1, pp. 132-143

Keywords 

CancerCell-based high throughput screeningJanus kinase/signal transducer and activator of transcriptionPlant extractsSmall molecule inhibitor

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.

ISSN 

0007-1048

Link 

http://dx.doi.org/10.1111/j.1365-2141.2009.07925.x

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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