Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 63, Issue 15, Pages 8584-8607Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.0c00988
Keywords
-
Categories
Ask authors/readers for more resources
The C-C chemokine receptor 4 (CCR4) is broadly expressed on regulatory T cells (T-reg) as well as other circulating and tissue-resident T cells. T-reg can be recruited to the tumor microenvironment (TME) through the C-C chemokines CCL17 and CCL22. T-reg accumulation in the TME has been shown to dampen the antitumor immune response and is thought to be an important driver in tumor immune evasion. Preclinical and clinical data suggest that reducing the T-reg population in the TME can potentiate the antitumor immune response of checkpoint inhibitors. We have developed small-molecule antagonists of CCR4, featuring a novel piperidinyl-azetidine motif; that inhibit the recruitment of T-reg into the TME and elicit antitumor responses as a single agent or in combination with an immune checkpoint blockade. The discovery of these potent, selective, and orally bioavailable CCR4 antagonists, and their activity in in vitro and in vivo models, is described herein.
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