TLR1/2 Specific Small-Molecule Agonist Suppresses Leukemia Cancer Cell Growth by Stimulating Cytotoxic T Lymphocytes.

ABSTRACT: Toll-like receptor 2 (TLR2) expressed on antigen presenting cells evokes a series of critical cytokines, which favor the development of tumor-specific cytotoxic T lymphocytes (CTLs). Therefore, TLR2 represents an attractive cancer immunotherapeutic target. Here, a synthetic library of 14 000 compounds together with a series of newly developed compounds for NF-κB activation using HEK-Blue hTLR2 cells is initially screened. Following further screening in a variety of cells including HEK-Blue hTLRs reporter cells, murine, and human macrophage cell lines, a potent small molecule agonist 23 (SMU-Z1) is identified, which specifically activates TLR2 through its association with TLR1, with a EC₅₀ of 4.88 ± 0.79 × 10^-9 m. Toxicology studies, proinflammatory cytokines (e.g., TN

SUBMITTER: Cen X 

PROVIDER: S-EPMC6523386 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature