Review Article

CBP/p300 bromodomain: new promising epigenetic target

¹ HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo 315000, China
² Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo 315000, China
³ International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Discovery of Chinese Ministry of Education (MOE), Guangzhou City Key Laboratory of Precision Chemical Drug Development, School of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China
⁴ Guangdong Provincial Key Laboratory of Biocomputing, Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, 510530, China
⁵ China-New Zealand Joint Laboratory on Biomedicine and Health, Guangzhou, 510530, China
⁶ State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China

^* Corresponding author: xu_yong@gibh.ac.cn

Received: 13 July 2022
Accepted: 17 August 2022

Abstract

CREB (cAMP responsive element binding protein) binding protein (CBP) and adenovirus E1A-associated 300 kDa protein (p300) are histone acetyltransferases, which are necessary for multiple cellular processes. Thus, CBP/p300 are promising potential antitumor targets. To date, despite various small molecule inhibitors of CBP/p300 bromodomain (BRD) having been reported, no specific inhibitor was approved by U.S. Food and Drug Administration (FDA). In this review, we described the discovery, optimization, binding mode evaluation, selectivity and potency evaluation, and therapeutic opportunities of our CBP/p300 bromodomain inhibitors, aiming to inspire new inhibitor design and advance drug discovery research in this field. One video presents the development of CBP/p300 bromodomain inhibitors.