Journal
CANCER CELL
Volume 36, Issue 5, Pages 483-+Publisher
CELL PRESS
DOI: 10.1016/j.ccell.2019.10.001
Keywords
-
Categories
Funding
- National Cancer Institute [R01CA123484, RO1CA196270, P50CA180995, P30CA060553]
- New-Cures Biomedical Accelerator of Northwestern University
- H-Foundation Multi-PI Basic Science Synergy Award
- Searle Funds at the Chicago Community Trust
- Chicago Biomedical Consortium
Ask authors/readers for more resources
Small molecules that directly target MYC and are also well tolerated in vivo will provide invaluable chemical probes and potential anti-cancer therapeutic agents. We developed a series of small-molecule MYC inhibitors that engage MYC inside cells, disrupt MYC/MAX dimers, and impair MYC-driven gene expression. The compounds enhance MYC phosphorylation on threonine-58, consequently increasing proteasome-mediated MYC degradation. The initial lead, MYC inhibitor 361 (MYCi361), suppressed in vivo tumor growth in mice, increased tumor immune cell infiltration, upregulated PD-L1 on tumors, and sensitized tumors to anti-PD1 immunotherapy. However, 361 demonstrated a narrow therapeutic index. An improved analog, MYCi975 showed better tolerability. These findings suggest the potential of small-moleculeMYC inhibitors as chemical probes and possible anti-cancer therapeutic agents.
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