Synthesis of urea analogues bearing N-alkyl-N'-(thiophen-2-yl) scaffold and evaluation of their innate immune response to toll-like receptors.
Eur J Med Chem
; 169: 42-52, 2019 May 01.
Article
en En
| MEDLINE
| ID: mdl-30852386
ABSTRACT
Previous high throughput virtual screening of 10 million-compound and following cell based validation led to the discovery of a novel, nonlipopeptide-like chemotype ZINC 6662436, as toll-like receptor 2 (TLR2) agonists. In this report, compounds belonging to four areas of structural modification of ZINC6662436 were evaluated for biological activity using human HEK-Blue TLR2 reporter cells, and human THP-1 monocytic cells, yield SMU-C13 as an optimized, direct and high potent (EC50â¯=â¯160â¯nM) agonist of human TLR2. Moreover, preliminary mechanism studies indicated that SMU-C13 through activates TLR1 and TLR2 then stimulates the NF-κB activation to trigger the downstream cytokines, such as TNF-α and secreted alkaline phosphatase (SEAP).
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tiofenos
/
Urea
/
Receptores Toll-Like
Límite:
Humans
Idioma:
En
Revista:
Eur J Med Chem
Año:
2019
Tipo del documento:
Article
País de afiliación:
China