TY  - JOUR
AU  - Šribar, Dora
AU  - Grabowski, Maria
AU  - Murgueitio, Manuela S.
AU  - Bermudez, Marcel
AU  - Weindl, Günther
AU  - Wolber, Gerhard
TI  - Identification and characterization of a novel chemotype for human TLR8 inhibitors
JO  - European journal of medicinal chemistry
VL  - 179
SN  - 0223-5234
CY  - Amsterdam [u.a.]
PB  - Elsevier10887
M1  - PUBDB-2020-00008
SP  - 744-752
PY  - 2019
N1  - © Elsevier Masson SAS. ; Final published version in progress; Post referee fulltext in progress; Embargo 12 months from publication
AB  - The endosomal Toll-like receptor 8 (TLR8) recognizes single-stranded RNA and initiates early inflammatory responses. Despite the importance of endosomal TLRs for human host defense against microbial pathogens, extensive activation may contribute to autoimmune and inflammatory diseases. In contrast to the recent progress made in the development of modulators of plasma membrane-bound TLRs, little is known about endosomal TLR modulation and very few TLR8 inhibitors have been reported. In this study, we discovered and validated novel small-molecule TLR8 inhibitors. Fourteen potential TLR8 modulators were experimentally validated in HEK293T cells stably overexpressing human TLR8 and THP-1 macrophages. Five compounds inhibited TLR8-mediated signaling, representing a hit rate of 36
LB  - PUB:(DE-HGF)16
C6  - pmid:31284084
UR  - <Go to ISI:>//WOS:000486133100055
DO  - DOI:10.1016/j.ejmech.2019.06.084
UR  - https://bib-pubdb1.desy.de/record/430316
ER  -