In:
Stem Cells Translational Medicine, Oxford University Press (OUP), Vol. 10, No. 3 ( 2021-03-01), p. 455-464
Abstract:
Nakajo-Nishimura syndrome (NNS) is an autoinflammatory disorder caused by a homozygous mutations in the PSMB8 gene. The administration of systemic corticosteroids is partially effective, but continuous treatment causes severe side effects. We previously established a pluripotent stem cell (PSC)-derived NNS disease model that reproduces several inflammatory phenotypes, including the overproduction of monocyte chemoattractant protein-1 (MCP-1) and interferon gamma-induced protein-10 (IP-10). Here we performed high-throughput compound screening (HTS) using this PSC-derived NNS model to find potential therapeutic candidates and identified CUDC-907 as an effective inhibitor of the release of MCP-1 and IP-10. Short-term treatment of CUDC-907 did not induce cell death within therapeutic concentrations and was also effective on primary patient cells. Further analysis indicated that the inhibitory effect was post-transcriptional. These findings suggest that HTS with PSC-derived disease models is useful for finding drug candidates for autoinflammatory diseases.
Type of Medium:
Online Resource
ISSN:
2157-6564
,
2157-6580
DOI:
10.1002/sctm.20-0198
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2021
detail.hit.zdb_id:
2642270-0