1. 负责人简介

姓名：向秋萍

电子邮件：xiang_qiuping@126.com

学习经历：

2009年09月-2013年06月  湖南师范大学 学士

2013年09月-2016年06月  中国科学院广州生物医药与健康研究院 硕士

2016年09月-2019年06月  中国科学院广州生物医药与健康研究院 博士

工作经历：

2019年07月-2021年06月  中国科学院广州生物医药与健康研究院 博士后

2019年10月-2020年08月  威斯康星大学麦迪逊分校 博士后

2021年07月-2022年03月  中国科学院广州生物医药与健康研究院 助理研究员、副研究员

2022年04月-至今          国科宁波生命与健康产业研究院 副研究员

2. 研究方向

抗肿瘤小分子药物研发

人工智能药物筛选

3. 发表论著

[1] Qiuping Xiang# Chao Wang,# Tianbang Wu,# Cheng Zhang, Qingqing Hu, Guolong Luo, Jiankang Hu, Xiaoxi Zhuang, Lingjiao Zou, Hui Shen, Xishan Wu, Yan Zhang, Xiangqian Kong, Jinsong Liu, and Yong Xu*. Design, Synthesis, and Biological Evaluation of 1-(Indolizin-3-yl)ethan-1-ones as CBP Bromodomain Inhibitors for the Treatment of Prostate Cancer. Journal of Medicinal Chemistry, 2022, 65, 785–810.

[2] Qiuping Xiang#,* Guolong Luo# Cheng Zhang, Qingqing Hu, Chao Wang, Tianbang Wu, Hongrui Xu, Jiankang Hu, Xiaoxi Zhuang, Maofeng Zhang, Shuang Wu, Jinxin Xu, Yan Zhang, Jinsong Liu, and Yong Xu*. Discovery, optimization and evaluation of 1-(indolin-1-yl)ethan-1-ones as novel selective TRIM24/BRPF1 bromodomain inhibitors. European Journal of Medicinal Chemistry, 2022, 236:114311.

[3] Qiuping Xiang, Yang Zhou, Yan Zhang, and Yong Xu*. CBP/p300 bromodomain: new promising epigenetic target. Visualized Cancer Medicine 2022, 3, 3.

[4] Hongrui Xu, Guolong Luo, Tianbang Wu, Jiankang Hu, Chao Wang, Xishan Wu, Yan Zhang*, Yong Xu,*, and Qiuping Xiang*. Structural insights revealed by the cocrystal structure of CCS1477 in complex with CBP bromodomain. Biochemical and Biophysical Research Communications, 2022, 623:17–22

[5] Qiuping Xiang#, Chao Wang#, Yan Zhang, Xiaoqian Xue, Ming Song, Cheng Zhang, Chenchang Li, Chun Wu, Kuai Li, Xiaoyan Hui, Yulai Zhou, Jeff B. Smaill, Adam V. Patterson, Donghai Wu, Ke Ding, Yong Xu*. Discovery and optimization of 1-(1H-indol-1-yl)ethanone derivatives as CBP/EP300 bromodomain inhibitors for the treatment of castration resistant prostate cancer. European Journal of Medicinal Chemistry, 2018, 147, 238−252.

[6] Qiuping Xiang#, Yan Zhang#, Jiaguo Li#, Xiaoqian Xue, Chao Wang, Ming Song, Cheng Zhang, Rui Wang, Chenchang Li, Chun Wu, Yulai Zhou, Xiaohong Yang, Guohui Li, Ke Ding, and Yong Xu*. Y08060: a selective BET inhibitor for treatment of prostate cancer. ACS Medicinal Chemistry Letters, 2018, 9, 262−267.

[7] Lingjiao Zou#, Qiuping Xiang#, Xiaoqian Xue#, Cheng Zhang, Chenchang Li, Chao Wang, Qiu Li, Rui Wang, Shuang Wu, Yulai Zhou, Yan Zhang, and Yong Xu*. Y08197, a novel and selective CBP and EP300 bromodomain inhibitor for treatment of prostate cancer. Acta Pharmacologica Sinica, 2019, 40, 1436−1447.

[8] Tianbang Wu#, Qiuping Xiang#, Chao Wang#, Chun Wu, Cheng Zhang, Maofeng Zhang, Zhaoxuan Liu, Yan Zhang*, Lin-jiu Xiao*, and Yong Xu*. Y06014 is a selective BET inhibitor for the treatment of prostate cancer. Acta Pharmacologica Sinica, 2021, 42, 2120−2131.

[9] Junjian Wang, June X Zou, Xiaoqian Xue, Demin Cai, Yan Zhang, Zhijian Duan, Qiuping Xiang, Joy C Yang, Maggie C Louie, Alexander D Borowsky, Allen C Gao, Christopher P Evans, Kit S Lam, Jianzhen Xu, Hsing-Jien Kung, Ronald M Evans, Yong Xu*, and Hongwu Chen*. ROR-γ drives androgen receptor expression and represents a therapeutic target in castration-resistant prostate cancer. Nature Medicine, 2016, 22, 488−496.

[10] Mao-feng Zhang, Xiao-yu Luo, Cheng Zhang, Chao Wang, Xi-shan Wu, Qiu-ping Xiang, Yong Xu* and Yan Zhang*. Design, synthesis and pharmacological characterization of N-(3-ethylbenzo[d]isoxazol-5-yl) sulfonamide derivatives as BRD4 inhibitors against acute myeloid leukemia. 2022, 43, 2735-2748.

[11] Qiu Li, # Benqiang Yao, # Shiting Zhao, Zhou Lu, Yan Zhang, Qiuping Xiang, Xishan Wu, Haonan Yu, Cheng Zhang, Junhua Li, Xiaoxi Zhuang, Donghai Wu, Yong Li*, Yong Xu*. Discovery of a Highly Selective and H435R-Sensitive Thyroid Hormone Receptor β Agonist

[12] Xishan Wu,# Hui Shen,# Yan Zhang,# Chao Wang, Qiu Li, Cheng Zhang, Xiaoxi Zhuang, Chenchang Li, Yudan Shi, Yanli Xing, Qiuping Xiang, Jinxin Xu, Donghai Wu, Jinsong Liu, and Yong Xu*. Discovery and Characterization of Benzimidazole Derivative XY123 as a Potent, Selective, and Orally Available RORγ Inverse Agonist. Journal of Medicinal Chemistry, 2021, 64, 8775-8797.

[13] Qingqing Hu, Chao Wang, Qiuping Xiang, Rui Wang, Cheng Zhang, Maofeng Zhang , Xiaoqian Xue, Guolong Luo , Xiaomin Liu , Xishan Wu , Yan Zhang, Donghai Wu, and Yong Xu*. Discovery and optimization of novel N-benzyl-3,6-dimethylbenzo[d] isoxazol-5-amine derivatives as potent and selective TRIM24 bromodomain inhibitors with potential anti-cancer activities. Bioorganic Chemistry, 2020, 94, 10342. 

[14] Dongsheng Zhu#, Huocong Huang#, Daniel M. Pinkas#, Jinfeng Luo, Debolina Ganguly, Alice E. Fox, Emily Arner, Qiuping Xiang, Zhengchao Tu, Alex N. Bullock*, Rolf A. Brekken*, Ke Ding*, and Xiaoyun Lu*. 2-Amino-2,3-dihydro‑1H‑indene-5-carboxamide-based discoidin domain receptor 1 (DDR1) inhibitors: design, synthesis, and in vivo antipancreatic cancer efficacy. Journal of Medicinal Chemistry, 2019, 62, 7431−7444.

[15] Maofeng Zhang#, Yan Zhang#, Ming Song#, Xiaoqian Xue, Junjian Wang, Chao Wang, Cheng Zhang, Chenchang Li, Qiuping Xiang, Lingjiao Zou, Xishan Wu, Chun Wu, Baijun Dong, Wei Xue, Yulai Zhou, Hongwu Chen, Donghai Wu, Ke Ding, and Yong Xu*. Structure-based discovery and optimization of benzo[d]isoxazole derivatives as potent and selective BET inhibitors for potential treatment of castration-resistant prostate cancer (CRPC). Journal of Medicinal Chemistry, 2018, 61, 3037−3058.

[16] Zhen Wang#, Yali Zhang#, Daniel M. Pinkas#, Alice E. Fox, Jinfeng Luo, Huocong Huang, Shengyang Cui, Qiuping Xiang, Tingting Xu, Qiuju Xun, Dongsheng Zhu, Zhengchao Tu, Xiaomei Ren, Rolf A. Brekken, Alex N. Bullock, Guang Liang*,  Ke Ding*, and Xiaoyun Lu*. Design, synthesis, and biological evaluation of 3-(imidazo[1,2-a]pyrazin-3-ylethynyl)-4-isopropyl-N-(3-((4-methylpiperazin-1-yl)methyl)-5-(trifluoromethyl)phenyl)benzamide as a dual inhibitor of discoidin domain receptors 1 and 2. Journal of Medicinal Chemistry, 2018, 61, 7977−7990.

[17] Xiaoqian Xue, Yan Zhang, Chao Wang, Maofeng Zhang, Qiuping Xiang, Junjian Wang, Anhui Wang, Chenchang Li, Cheng Zhang, Lingjiao Zou, Rui Wang, Shuang Wu, Yongzhi Lu, Hongwu Chen, Ke Ding, Guohui Li, Yong Xu*. Benzoxazinone-containing 3,5-dimethylisoxazole derivatives as BET bromodomain inhibitors for treatment of castration-resistant prostate cancer. European Journal of Medicinal Chemistry, 2018, 152, 542−559.

[18] Xiaoqian Xue#, Yan Zhang#, Zhaoxuan Liu#, Ming Song, Yanli Xing, Qiuping Xiang, Zhen Wang, Zhengchao Tu, Yulai Zhou, Ke Ding, and Yong Xu*. Discovery of benzo[cd]indol-2(1H)-ones as potent and specific BET bromodomain inhibitors: structure-based virtual screening, optimization, and biological evaluation. Journal of Medicinal Chemistry, 2016, 59, 1565−1579.

4. 承担科研项目

国家自然科学青年基金，主持，项目批准号：22007088。

中国博士后科学基金面上项目，主持，项目批准号：2019M663145。

广东省基础与应用基础研究基金面上项目，主持，项目批准号：2021A1515010085。

广东省基础与应用基础研究基金青年项目，主持，项目批准号：2019A1515110592。

宁波市自然科学基金，主持，项目批准号：2022J272。

5. 项目组简介

组蛋白的乙酰化修饰是表观遗传学中重要的翻译后修饰之一。组蛋白尾部的赖氨酸发生乙酰化修饰，可以招募溴结构域（Bromodomain，BRD）进行转录复合物的组装。因此，溴结构域充当了乙酰化赖氨酸的识别器，进而调控基因表达。溴结构域蛋白已经被证明与多种癌症、炎症或病毒感染等疾病相关。

本课题组利用计算机辅助药物设计、化学生物学、药理学等技术开展BRD抑制剂的发现工作。