Journal
CANCER CELL
Volume 27, Issue 4, Pages 589-602Publisher
CELL PRESS
DOI: 10.1016/j.ccell.2015.02.016
Keywords
-
Categories
Funding
- National Institutes of Health (NIH) [1R01CA160467, HD007505, GM007315]
- Leukemia and Lymphoma Society (LLS) TRP grant [6116-12]
- LLS [1215-14]
- LLS Therapy Acceleration Program
- American Cancer Society [RSG-11-082-01-DMC, RSG-13-130-01-CDD]
- Department of Pathology, University of Michigan
- USA Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-AC02-06CH11357]
- Michigan Economic Development Corporation
- Michigan Technology Tri-Corridor [085P1000817]
Ask authors/readers for more resources
Chromosomal translocations affecting mixed lineage leukemia gene (MLL) result in acute leukemias resistant to therapy. The leukemogenic activity of MLL fusion proteins is dependent on their interaction with menin, providing basis for therapeutic intervention. Here we report the development of highly potent and orally bioavailable small-molecule inhibitors of the menin-MLL interaction, MI-463 and MI-503, and show their profound effects in MLL leukemia cells and substantial survival benefit in mousemodels of MLL leukemia. Finally, we demonstrate the efficacy of these compounds in primary samples derived from MLL leukemia patients. Overall, we demonstrate that pharmacologic inhibition of the menin-MLL interaction represents an effective treatment for MLL leukemias in vivo and provide advanced molecular scaffold for clinical lead identification.
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