Journal of Medicinal Chemistry p. 10151 - 10171 (2017)
Update date:2022-08-16
Topics:
Bronner, Sarah M.
Murray, Jeremy
Romero, F. Anthony
Lai, Kwong Wah
Tsui, Vickie
Cyr, Patrick
Beresini, Maureen H.
De Leon Boenig, Gladys
Chen, Zhongguo
Choo, Edna F.
Clark, Kevin R.
Crawford, Terry D.
Jayaram, Hariharan
Kaufman, Susan
Li, Ruina
Li, Yingjie
Liao, Jiangpeng
Liang, Xiaorong
Liu, Wenfeng
Ly, Justin
Maher, Jonathan
Wai, John
Wang, Fei
Zheng, Aijun
Zhu, Xiaoyu
Magnuson, Steven
The epigenetic regulator CBP/P300 presents a novel therapeutic target for oncology. Previously, we disclosed the development of potent and selective CBP bromodomain inhibitors by first identifying pharmacophores that bind the KAc region and then building into the LPF shelf. Herein, we report the "hybridization" of a variety of KAc-binding fragments with a tetrahydroquinoline scaffold that makes optimal interactions with the LPF shelf, imparting enhanced potency and selectivity to the hybridized ligand. To demonstrate the utility of our hybridization approach, two analogues containing unique Asn binders and the optimized tetrahydroquinoline moiety were rapidly optimized to yield single-digit nanomolar inhibitors of CBP with exquisite selectivity over BRD4(1) and the broader bromodomain family.
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Doi:10.1080/00397911.2014.997368
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