Dataset Information

A High-Content Screen for Mucin-1-Reducing Compounds Identifies Fostamatinib as a Candidate for Rapid Repurposing for Acute Lung Injury.

ABSTRACT: 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.

SUBMITTER: Kost-Alimova M

PROVIDER: S-EPMC7691435 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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A High-Content Screen for Mucin-1-Reducing Compounds Identifies Fostamatinib as a Candidate for Rapid Repurposing for Acute Lung Injury.

Kost-Alimova Maria M Sidhom Eriene-Heidi EH Satyam Abhigyan A Chamberlain Brian T BT Dvela-Levitt Moran M Melanson Michelle M Alper Seth L SL Santos Jean J Gutierrez Juan J Subramanian Ayshwarya A Byrne Patrick J PJ Grinkevich Elizabeth E Reyes-Bricio Estefanía E Kim Choah C Clark Abbe R AR Watts Andrew J B AJB Thompson Rebecca R Marshall Jamie J Pablo Juan Lorenzo JL Coraor Juliana J Roignot Julie J Vernon Katherine A KA Keller Keith K Campbell Alissa A Emani Maheswarareddy M Racette Matthew M Bazua-Valenti Silvana S Padovano Valeria V Weins Astrid A McAdoo Stephen P SP Tam Frederick W K FWK Ronco Luciene L Wagner Florence F Tsokos George C GC Shaw Jillian L JL Greka Anna A

Cell reports. Medicine 20201029 8

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 ...[more]

PMID: 33294858

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Dataset Information

A High-Content Screen for Mucin-1-Reducing Compounds Identifies Fostamatinib as a Candidate for Rapid Repurposing for Acute Lung Injury.

Publications

A High-Content Screen for Mucin-1-Reducing Compounds Identifies Fostamatinib as a Candidate for Rapid Repurposing for Acute Lung Injury.

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