Nature Communications (May 2021)
Discovery of first-in-class inhibitors of ASH1L histone methyltransferase with anti-leukemic activity
- David S. Rogawski,
- Jing Deng,
- Hao Li,
- Hongzhi Miao,
- Dmitry Borkin,
- Trupta Purohit,
- Jiho Song,
- Jennifer Chase,
- Shuangjiang Li,
- Juliano Ndoj,
- Szymon Klossowski,
- EunGi Kim,
- Fengbiao Mao,
- Bo Zhou,
- James Ropa,
- Marta Z. Krotoska,
- Zhuang Jin,
- Patricia Ernst,
- Xiaomin Feng,
- Gang Huang,
- Kenichi Nishioka,
- Samantha Kelly,
- Miao He,
- Bo Wen,
- Duxin Sun,
- Andrew Muntean,
- Yali Dou,
- Ivan Maillard,
- Tomasz Cierpicki,
- Jolanta Grembecka
Affiliations
- David S. Rogawski
- Department of Pathology, University of Michigan
- Jing Deng
- Department of Pathology, University of Michigan
- Hao Li
- Department of Pathology, University of Michigan
- Hongzhi Miao
- Department of Pathology, University of Michigan
- Dmitry Borkin
- Department of Pathology, University of Michigan
- Trupta Purohit
- Department of Pathology, University of Michigan
- Jiho Song
- Department of Pathology, University of Michigan
- Jennifer Chase
- Life Sciences Institute, University of Michigan
- Shuangjiang Li
- Department of Pathology, University of Michigan
- Juliano Ndoj
- Department of Pathology, University of Michigan
- Szymon Klossowski
- Department of Pathology, University of Michigan
- EunGi Kim
- Department of Pathology, University of Michigan
- Fengbiao Mao
- Department of Pathology, University of Michigan
- Bo Zhou
- Department of Pathology, University of Michigan
- James Ropa
- Department of Pathology, University of Michigan
- Marta Z. Krotoska
- Department of Pathology, University of Michigan
- Zhuang Jin
- Department of Pathology, University of Michigan
- Patricia Ernst
- Department of Pediatrics, University of Colorado Denver, Anschutz Medical Campus
- Xiaomin Feng
- Department of Pathology and Laboratory Medicine, Cincinnati Children’s Hospital
- Gang Huang
- Department of Pathology and Laboratory Medicine, Cincinnati Children’s Hospital
- Kenichi Nishioka
- Department of Internal Medicine Musashimurayama Hospital, Enoki 1-1-5, Musashimurayama
- Samantha Kelly
- Division of Hematology-Oncology, Perelman School of Medicine, University of Pennsylvania
- Miao He
- College of Pharmacy, University of Michigan
- Bo Wen
- College of Pharmacy, University of Michigan
- Duxin Sun
- College of Pharmacy, University of Michigan
- Andrew Muntean
- Department of Pathology, University of Michigan
- Yali Dou
- Department of Pathology, University of Michigan
- Ivan Maillard
- Life Sciences Institute, University of Michigan
- Tomasz Cierpicki
- Department of Pathology, University of Michigan
- Jolanta Grembecka
- Department of Pathology, University of Michigan
- DOI
- https://doi.org/10.1038/s41467-021-23152-6
- Journal volume & issue
-
Vol. 12,
no. 1
pp. 1 – 14
Abstract
The histone methyltransferase ASH1L plays a role in various diseases, including cancer, and has been validated as a therapeutic target; however, no inhibitors of ASH1L have been reported. Here the authors present small molecule inhibitors of ASH1L and demonstrate their on-target activity in leukemia cells and a mouse model of leukemia.
