Journal
FRONTIERS IN PHARMACOLOGY
Volume 11, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2020.00237
Keywords
HTS; small molecule; sulfonyl compound; T cells; cancer; apoptosis
Categories
Funding
- Merck Frosst Start-up funds [RH000569]
- Universite de Montreal
- Merck Sharp Dohme Corp [SFMERE58]
- Fonds de la Recherche en Sante du Quebec Junior II Award
Ask authors/readers for more resources
Phenotypic screening is an ideal strategy for the discovery of novel bioactive molecules. Using a customized high-throughput screening (HTS) assay employing primary T lymphocytes, we screened a small library of 4,398 compounds with unknown biological function/target to identify compounds eliciting immunomodulatory properties and discovered a sulfonyl-containing hit, we named InhiTinib. This compound inhibited interferon (IFN)-gamma production and proliferation of primary CD3(+) T cells without inducing cell death. In contrast, InhiTinib triggered apoptosis in several murine and human cancer cell lines. Besides, the compound was well tolerated by immunocompetent mice, triggered tumor regression in animals with pre-established EL4 T-cell lymphomas, and prolonged the overall survival of mice harboring advanced tumors. Altogether, our data demonstrate the anti-cancer properties of InhiTinib, which can henceforth bridge to wider-scale biochemical and clinical tests following further in-depth pharmacodynamic studies.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available