Imperial College London
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ProfessorFrederickTam

Faculty of Medicine, Department of Immunology and Inflammation

Ken and Mary Minton Chair of Renal Medicine
 
 
 
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Contact

 

+44 (0)20 3313 2354f.tam

 
 
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Location

 

9N, 15C, Commonwealth BuildingHammersmith HospitalHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Kost-Alimova:2020:10.1016/j.xcrm.2020.100137,
author = {Kost-Alimova, M and Sidhom, E-H and Satyam, A and Chamberlain, BT and Dvela-Levitt, M and Melanson, M and Alper, SL and Santos, J and Gutierrez, J and Subramanian, A and Byrne, PJ and Grinkevich, E and Bricio, ER and Kim, C and Clark, A and Watts, A and Thompson, R and Marshall, J and Pablo, JL and Coraor, J and Roignot, J and Vernon, KA and Keller, K and Campbell, A and Emani, M and Racette, M and Bazua-Valenti, S and Padovano, V and Weins, A and McAdoo, SP and Tam, FWK and Ronco, L and Wagner, F and Tsokos, GC and Shaw, JL and Greka, A},
doi = {10.1016/j.xcrm.2020.100137},
journal = {Cell Reports Medicine},
pages = {1--15},
title = {A high content screen for mucin-1-reducing compounds identifies fostamatinib as a candidate for rapid repurposing for acute lung injury},
url = {http://dx.doi.org/10.1016/j.xcrm.2020.100137},
volume = {1},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Drug repurposing has the advantage of identifying potential treatments on a shortened timescale. In response to the pandemic spread of SARS-CoV-2, we took advantage of a high-content screen of 3,713 compounds at different stages of clinical development to identify FDA-approved compounds that reduce mucin-1 (MUC1) protein abundance. Elevated MUC1 levels predict the development of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) and correlate with poor clinical outcomes. Our screen identifies fostamatinib (R788), an inhibitor of spleen tyrosine kinase (SYK) approved for the treatment of chronic immune thrombocytopenia, as a repurposing candidate for the treatment of ALI. In vivo, fostamatinib reduces MUC1 abundance in lung epithelial cells in a mouse model of ALI. In vitro, SYK inhibition by the active metabolite R406 promotes MUC1 removal from the cell surface. Our work suggests fostamatinib as a repurposing drug candidate for ALI.
AU  - Kost-Alimova,M
AU  - Sidhom,E-H
AU  - Satyam,A
AU  - Chamberlain,BT
AU  - Dvela-Levitt,M
AU  - Melanson,M
AU  - Alper,SL
AU  - Santos,J
AU  - Gutierrez,J
AU  - Subramanian,A
AU  - Byrne,PJ
AU  - Grinkevich,E
AU  - Bricio,ER
AU  - Kim,C
AU  - Clark,A
AU  - Watts,A
AU  - Thompson,R
AU  - Marshall,J
AU  - Pablo,JL
AU  - Coraor,J
AU  - Roignot,J
AU  - Vernon,KA
AU  - Keller,K
AU  - Campbell,A
AU  - Emani,M
AU  - Racette,M
AU  - Bazua-Valenti,S
AU  - Padovano,V
AU  - Weins,A
AU  - McAdoo,SP
AU  - Tam,FWK
AU  - Ronco,L
AU  - Wagner,F
AU  - Tsokos,GC
AU  - Shaw,JL
AU  - Greka,A
DO  - 10.1016/j.xcrm.2020.100137
EP  - 15
PY  - 2020///
SN  - 2666-3791
SP  - 1
TI  - A high content screen for mucin-1-reducing compounds identifies fostamatinib as a candidate for rapid repurposing for acute lung injury
T2  - Cell Reports Medicine
UR  - http://dx.doi.org/10.1016/j.xcrm.2020.100137
UR  - https://www.sciencedirect.com/science/article/pii/S2666379120301816?via%3Dihub
UR  - http://hdl.handle.net/10044/1/83980
VL  - 1
ER  -
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