2024.6-至今      中国科学院生物与化学交叉研究中心，研究员、课题组长

2020.1-2024.5  美国密歇根大学医学院，博士后

2019.7-2020.1  中国科学院上海有机化学研究所，助理研究员

2016.9-2019.6  中国科学院上海有机化学研究所，有机化学博士

2013.9-2016.6  南昌大学/中国科学院上海药物研究所，药物化学硕士

2012.7-2013.8  中国科学院上海药物研究所，本科毕业设计

2009.9-2013.7  南昌大学，药学本科

陈志翔研究员长期从事靶向蛋白降解的新药研发和药物合成方法学的研究。一方面，通过对分子的理性设计、精准调控和修饰，解决了PROTAC药物的口服吸收难题和分子胶药物的脱靶问题，成功开发了靶向CBP/p300、ERα、IKZF2等不同靶标的多款可口服且安全有效的临床候选药物，并揭示了CBP/p300降解剂的独特作用机制。另一方面，针对一些常见类型药物的合成问题，发展了一系列廉价铜/新型配体催化的高效C-O和C-N偶联方法，得到了广泛关注和应用。相关工作以第一作者发表于J Am Chem Soc（ESI高被引）、J Med Chem（3篇，1篇亮点文章）、Org Lett等著名期刊，还有多篇第一/共同第一作者文章已投稿，其中2篇投稿至J Med Chem期刊的文章小修后即可接收。此外，以第一或导师外第一（7项）、第二或导师外第二（4项）等发明人身份申请国际/美国专利16项，大部分专利已许可/转让给美国Proteovant公司（已更名为SK Life Science Labs）进行后续临床开发。

（1）靶向蛋白降解的抗神经退行性疾病的药物发现和成药性优化；

（2）基于分子胶技术的药物开发及其作用机制研究；

（3）针对潜在新靶标的小分子调节剂的开发和化学生物学研究；

（4）铜催化偶联反应的第三代高效配体的开发及其在药物合成中的应用。

1. Zhixiang Chen, Yongwen Jiang, Li Zhang, Yinlong Guo, Dawei Ma. Oxalic diamides and tert-butoxides: Two types of ligands enabling practical access to alkyl aryl ethers via Cu-catalyzed coupling reaction. Journal of the American Chemical Society, 2019, 141, 3541. (ESI高被引论文)

2. Zhixiang Chen,^# Mi Wang,^# Dimin Wu,^# Longchuan Bai, Tianfeng Xu, Hoda Metwally, Yu Wang, Donna McEachern, Lijie Zhao, Ruiting Li, John Takyi-Williams, Meilin Wang, Lu Wang, Qiuxia Li, Bo Wen, Duxin Sun, Shaomeng Wang. Discovery of CBPD-268 as an exceptionally potent and orally efficacious CBP/p300 PROTAC degrader capable of achieving tumor regression. Journal of Medicinal Chemistry, 2024, 67, 5275. (被评为“Featured Article”)

3. Zhixiang Chen,^# Mi Wang,^# Dimin Wu, Lijie Zhao, Hoda Metwally, Wei Jiang, Yu Wang, Longchuan Bai, Donna McEachern, Jie Luo, Meilin Wang, Qiuxia Li, Aleksas Matvekas, Bo Wen, Duxin Sun, Arul M Chinnaiyan, Shaomeng Wang. Discovery of CBPD-409 as a highly potent, selective, and orally efficacious CBP/p300 PROTAC degrader for the treatment of advanced prostate cancer. Journal of Medicinal Chemistry, 2024, 67, 5351.

4. Zhixiang Chen,^# Biao Hu,^# Rohan Kalyan Rej,^# Dimin Wu,^# Ranjan Kumar Acharyya,^# Mingliang Wang,^# Tianfeng Xu,^# Jianfeng Lu, Hoda Metwally, Yu Wang, Donna McEachern, Longchuan Bai, Christina L Gersch, Meilin Wang, Wenjing Zhang, Qiuxia Li, Bo Wen, Duxin Sun, James M Rae, Shaomeng Wang. Discovery of ERD-3111 as a potent and orally Efficacious estrogen receptor PROTAC degrader with strong antitumor activity. Journal of Medicinal Chemistry, 2023, 66, 12559.

5. Jie Luo,^# Zhixiang Chen,^# Yuanyuan Qiao,^# Jean Ching-Yi Tien, Eleanor Young, Rahul Mannan, Somnath Mahapatra, Tongchen He, Sanjana Eyunni, Yuping Zhang, Yang Zheng, Fengyun Su, Xuhong Cao, Rui Wang, Yunhui Cheng, Rithvik Seri, James George, Miriam Shahine, Stephanie J. Miner, Ulka Vaishampayan, Mi Wang, Shaomeng Wang, Abhijit Parolia, Arul M. Chinnaiyan. p300/CBP degradation is required to disable the active AR enhanceosome in prostate cancer. (bioRxiv, doi: https://doi.org/10.1101/2024.03.29.587346)

6. Zhixiang Chen and Dawei Ma. Cu/N,N^’-dibenzyloxalamide catalyzed N-arylation of heteroanilines. Organic Letters, 2019, 21, 6874.

7. Zhixiang Chen,^# Harshil Dhruv,^# Xuqing Zhang,^# Longchuan Bai,^# Rohan Kalyan Rej, Donna McEachern, Paul Kirchhoff, Rakesh Nagilla, Larry J. Jolivette, Cory T. Rice, Peter Orth, Corey O. Strickland, E. Scott Priestley, Helai P. Mohammad, Meilin Wang, Wenjing Zhang, Alejandra Duran, Bo Wen, Duxin Sun, Zhihua Sui, Shaomeng Wang. PVTX-405: a Potent, Highly Selective, and Orally Efficacious Molecular Glue Degrader of IKZF2 for the Treatment of Human Cancers. (Submitted to Nature Communications)

8. Rohan Kalyan Rej,^# Biao Hu,^# Zhixiang Chen,^# Ranjan Kumar Acharyya,^# Dimin Wu,^# Hoda Metwally, Yu Wang, Wei Jiang, Longchuan Bai, Lorraine-Gersch Clark, Guozhang Xu, Weihong Zhang, Winston Wu, Scott Priestley, Zhihua Sui, Meilin Wang, Bo Wen, Duxin Sun, James M. Rae, Shaomeng Wang. Discovery of ERD-12310A as a Highly Potent and Orally Efficacious PROTAC Degrader of Estrogen Receptor α (ERα) for the Treatment of ER+ Human Breast Cancer. Journal of Medicinal Chemistry, 2024. (To be accepted after minor revision)

9. Ranjan Kumar Acharyya,^# Rohan Kalyan Rej,^# Biao Hu,^# Zhixiang Chen,^# Dimin Wu,^# Jianfeng Lu, Hoda Metwally, Donna McEachern, Yu Wang, Wei Jiang, Longchuan Bai, Jelena Tosovic, Lorraine-Gersch Clark, Guozhang Xu, Weihong Zhang, WenXue Wu, E. Scott Priestley, Zhihua Sui, Farzad Sarkari, Bo Wen, Duxin Sun, James M. Rae, Shaomeng Wang. Discovery of ERD-1233 as a Potent and Orally Efficacious Estrogen Receptor PROTAC Degrader for the Treatment of ER+ Human Breast Cancer. Journal of Medicinal Chemistry, 2024. (To be accepted after minor revision)

10. Zhixiang Chen, Mengmeng Ning, Qingan Zou, Hua Cao, Yangliang Ye, Ying Leng, Jianhua Shen. Discovery and structure–activity relationship study of 4-phenoxythiazol-5-carboxamides as highly potent TGR5 agonists. Chemical and Pharmaceutical Bulletin, 2016, 64, 326.

11. Hua Cao, Zhi-Xiang Chen, Kai Wang, Meng-Meng Ning, Qing-An Zou, Ying Feng, Yang-Liang Ye, Ying Leng, Jian-Hua Shen. Intestinally-targeted TGR5 agonists equipped with quaternary ammonium have an improved hypoglycemic effect and reduced gallbladder filling effect. Scientific Reports, 2016, 6, 28676.