Medicinal Chemistry and Drug Discovery
Principal investigator
Name:
Jianjun ChengAssociate Professor , PhD, Associate Professor
Position:
Affiliation:
Honor:
Education Background:
- 2001/09-2005/06, Shandong University, BS
- 2005/09-2010/07, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Ph.D.
Working Experience:
- 2010/07-2013/10, Shanghai Huilun Life Sciences & Technology, Senior Scientist
- 2013/11-2016/03, University of Illinois at Chicago, Postdoctoral Research Associate
- 2016/03-2022/06, ShanghaiTech University, iHuman Institute, Principal Investigator
- 2022/07-present, ShanghaiTech University, School of Life Science and Technology/iHuman Institute, Assistant Professor (TENURE-TRACK)
Group Introduction
Research Area:
GPCR-targeted drug discovery
Research Interests:
The research of our group is focused on GPCR-targeted medicinal chemistry and drug discovery. We leverage the knowledge on the structures and functions of G protein-coupled receptors (GPCRs) for the design of novel drug-like compounds with therapeutic potential. A major focus is targeting aminergic and orphan GPCRs for the design of next-generation therapeutics for the treatment of neuropsychiatric disorders, in particular, depression and schizophrenia. From a medicinal chemistry perspective, our research goal is the design of novel drug-like compounds by addressing the following three scientific challenges in GPCR drug discovery: (1) Structure-based design of subtype-selective GPCR modulators; (2) Rational design of “biased” GPCR ligands that are functionally selective for a specific signaling pathway; (3) Rational design of GPCR ligands with desired polypharmacological profiles. Our research is dedicated to developing innovative therapeutics that address critical unmet needs in neuropsychiatric disorder treatment.
Research Achievement
1. Structure-based discovery of non-hallucinogenic psychedelic analog IHCH-7086 as a novel antidepressant drug candidate (Science 2022). 2. Structure-based discovery of highly selective dopamine D2 receptor partial agonist IHCH-7041 as a novel preclinical anti-schizophrenia drug candidate (Nature Neuroscience 2022, cover story). 3. PCPMA-based highly selective serotonin 2C agonists with anti-schizophrenia effects (J Med Chem 2015; 2016a; 2016b); highly selective dopamine D3 ligands (J Med Chem 2020); and dopamine D2 partial agonists with anti-schizophrenia effects (J Med Chem 2021). 4. Discovery of dual-acting tumor immunotherapeutics targeting the adenosine A2a receptor and histone deacetylases (J Med Chem 2021; Eur J Med Chem 2022).
Representative Publications (*First Author, # Corresponding Author)
- 1. Duan, Wenwen*; Cao, Dongmei; Wang, Wang, Sheng#; Cheng, Jianjun#.Serotonin 2A Receptor (5-HT2AR) Agonists: Psychedelics and Non-Hallucinogenic Analogues as Emerging Antidepressants.CHEMICAL REVIEWS. 2024. 124(1): 124-163.
- 2. Chen, Zhangcheng*; Yu, Jing; Wang, Huan; Xu, Peiyu; Fan, Luyu; Sun, Fengxiu; Huang, Sijie; Zhang, Pei; Huang, He; Gu, Shuo; Zhang, Bowen; Zhou, Yue; Wan, Xiaobo; Pei, Gang; Xu, H. Eric#; Cheng, Jianjun#; Wang, Sheng#.Flexible scaffold-based cheminformatics approach for polypharmacological drug design.CELL. 25 Apr 2024. 187(9):2194-2208.e22.
- 3. Cao, Dongmei*; Yu, Jing; Wang, Huan; Luo, Zhipu; Liu, Xinyu; He, Licong; Qi, Jianzhong; Fan, Luyu; Tang, Lingjie; Chen, Zhangcheng; Li, Jinsong; Cheng, Jianjun#; Wang, Sheng#.Structure-based discovery of nonhallucinogenic psychedelic analogs.SCIENCE. 28 Jan 2022. 375(6579):403-411.
- 4. Yan, Wenzhong*#; Feng, Mingshun*; Yang, Kexin; Yu, Chengcheng; Zhang, Wenxin; Liu, Junjun; Xie, Chengying#; Cheng, Jianjun#.Pharmacokinetics-Driven Optimization of Immunotherapeutic Agents Targeting the Adenosine A2A Receptor (A2AR) and Histone Deacetylases (HDACs).JOURNAL OF MEDICINAL CHEMISTRY. 12 Mar 2026. 69(5):6038-6062.
- 5. Li, Rongyan*; Yan, Haohan; Chen, Yujin; Liu, Yangyang; Tang, Lingjie; Yu, Jing; Liu, Junjun; Wang, Huan; Wang, Sheng#; Cheng, Jianjun#.Structure-Guided Design of Novel 5-HT2A Partial Agonists as Psychedelic Analogues with Antidepressant Effects.JOURNAL OF MEDICINAL CHEMISTRY. 23 Oct 2025. 68(20):21683-21700.
- 6. Yao, Mingyue*; Yan, Wenzhong*; Wang, Yafang; Zhao, Yu; Xu, Xiaowei; Chen, Yujun; Yu, Chengcheng; Li, Yingnian; Jiang, Hualiang; Shen, Jie#; Cheng, Jianjun#; Xie, Chengying#.IHCH9033, a novel class I HDAC inhibitor, synergizes with FLT3 inhibitor and rescues quizartinib resistance in FLT3-ITD AML via enhancing DNA damage response.EXPERIMENTAL HEMATOLOGY & ONCOLOGY. 15 Feb 2025. 14(1).
- 7. Jianhang Mao*; Yilong Cui; Huan Wang; Wenwen Duan; Zhi-Jie Liu; Tian Hua*; Ning Zhou#; Jianjun Cheng#.Design and Synthesis of Novel GPR139 Agonists with Therapeutic Effects in Mouse Models of Social Interaction and Cognitive Impairment.JOURNAL OF MEDICINAL CHEMISTRY. 13 Oct 2023. 66(20):14011–14028.
- 8. Liu, Ruiquan*; Qi, Jianzhong; Wang, Huan; Fan, Luyu; Zhang, Pei; Yu, Jing; Tan, Liang; Wang, Sheng#; Cheng, Jianjun#.Transformation of a Dopamine D2 Receptor Agonist to Partial Agonists as Novel Antipsychotic Agents.JOURNAL OF MEDICINAL CHEMISTRY. 11 May 2023. 66(9):6274-6287.
- 9. Sun, Nan*; Yang, Kexin*; Yan, Wenzhong*; Yao, Mingyue; Xie, Chengying#; Cheng, Jianjun#; Yu, Chengcheng; Duan, Wenwen; Gu, Xiaoke; Guo, Dong; Jiang, Hualiang.Design and Synthesis of Triazole-Containing HDAC Inhibitors That Induce Antitumor Effects and Immune Response.JOURNAL OF MEDICINAL CHEMISTRY. 13 Apr 2023. 66(7):4802-4826.
- 10. Zhang, Jinfeng*; Feng, Dandan; Cheng, Jianjun#; Wüthrich, Kurt#.Adenosine A2AReceptor (A2AAR) Ligand Screening Using the 19F-NMR Probe FPPA.JOURNAL OF THE AMERICAN CHEMICAL SOCIETY. 05 Jun 2023. 145(28):15061-15064.
- 11. Gu, Xiaoke*; Yuan, Haoxing; Zhao, Wenchao; Sun, Nan; Yan, Wenzhong; Jiang, Chunyu; He, Yan; Liu, Hongli; Cheng, Jianjun#; Guo, Dong#.Optical-Controlled Kinetic Switch: Fine-Tuning of the Residence Time of an Antagonist Binding to the Vasopressin V2 Receptor in In Vitro, Ex Vivo, and In Vivo Models of ADPKD.JOURNAL OF MEDICINAL CHEMISTRY. 26 Jan 2023. 66(2):1454-1466.
- 12. Wang, Jingjing*; Wu, Meng*; Chen, Zhangcheng*; Wu, Lijie; Wang, Tian; Cao, Dongmei; Wang, Huan; Liu, Shenhui; Xu, Yueming; Li, Fei; Liu, Junlin; Chen, Na; Zhao, Suwen; Cheng, Jianjun#; Wang, Sheng#; Hua, Tian#.The unconventional activation of the muscarinic acetylcholine receptor M4R by diverse ligands.NATURE COMMUNICATIONS. 23 May 2022. 13(1).
- 13. Chen, Zhangcheng*; Fan, Luyu; Wang, Huan; Yu, Jing; Lu, Dengyu; Qi, Jianzhong; Nie, Fen; Luo, Zhipu; Liu, Zhen; Cheng, Jianjun#; Wang, Sheng#.Structure-based design of a novel third-generation antipsychotic drug lead with potential antidepressant properties.NATURE NEUROSCIENCE. Jan 2022. 25(1):39-49.
- 14. Zhang, Haoran*; Yan, Wenzhong; Sun, Yongzhan; Yuan, Haoxing; Su, Limin; Cao, Xudong; Wang, Peng; Xu, Zhou; Hu, Youhui; Wang, Zhongjian; Wang, Yinan; Fu, Kequan; Sun, Ying; Chen, Yupeng#; Cheng, Jianjun#; Guo, Dong#.Long Residence Time at the Vasopressin V-2 Receptor Translates into Superior Inhibitory Effects in Ex Vivo and In Vivo Models of Autosomal Dominant Polycystic Kidney Disease.JOURNAL OF MEDICINAL CHEMISTRY. 09 Jun 2022. 65(11):7717-7728.
- 15. Yan, Wenzhong*; Ling, Lijun*; Wu, Yiran; Yang, Kexin; Liu, Ruiquan; Zhang, Jinfeng; Zhao, Simeng; Zhong, Guisheng; Zhao, Suwen; Jiang, Hualiang#; Xie, Chengying#; Cheng, Jianjun#.Structure-Based Design of Dual-Acting Compounds Targeting Adenosine A(2A) Receptor and Histone Deacetylase as Novel Tumor Immunotherapeutic Agents.JOURNAL OF MEDICINAL CHEMISTRY. 25 Nov 2021. 64(22):16573-16597.
- 16. Yan, Wenzhong*; Fan, Luyu; Yu, Jing; Liu, Ruiquan; Wang, Huan; Tan, Liang; Wang, Sheng#; Cheng, Jianjun#.2-Phenylcyclopropylmethylamine Derivatives as Dopamine D-2 Receptor Partial Agonists: Design, Synthesis, and Biological Evaluation.JOURNAL OF MEDICINAL CHEMISTRY. 09 Dec 2021. 64(23):17239-17258.
- 17. Duan, Wenwen*; Sun, Ying; Wu, Meng; Zhang, Zhiyuan; Zhang, Taotao; Wang, Huan; Li, Fei; Yang, Lingyun; Xu, Yueming; Liu, Zhi-Jie; Hua, Tian#; Nie, Hong#; Cheng, Jianjun#.Carbon-silicon switch led to the discovery of novel synthetic cannabinoids with therapeutic effects in a mouse model of multiple sclerosis.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. 15 Dec 2021. 226.
- 18. Fan, Luyu*; Tan, Liang; Chen, Zhangcheng; Qi, Jianzhong; Nie, Fen; Luo, Zhipu; Cheng, Jianjun#; Wang, Sheng#.Haloperidol bound D-2 dopamine receptor structure inspired the discovery of subtype selective ligands.NATURE COMMUNICATIONS. 26 Feb 2020. 11(1).
- 19. Tan, Liang*; Zhou, Qingtong; Yan, Wenzhong; Sun, Jian; Kozikowski, Alan P.; Zhao, Suwen; Huang, Xi-Ping#; Cheng, Jianjun#.Design and Synthesis of Bitopic 2-Phenylcyclopropylmethylamine (PCPMA) Derivatives as Selective Dopamine D3 Receptor Ligands.JOURNAL OF MEDICINAL CHEMISTRY. 14 May 2020. 63(9):4579-4602.
- 20. Tan, Liang*; Yan, Wenzhong; McCorvy, John D.#; Cheng, Jianjun#.Biased Ligands of G Protein-Coupled Receptors (GPCRs): Structure-Functional Selectivity Relationships (SFSRs) and Therapeutic Potential.JOURNAL OF MEDICINAL CHEMISTRY. 22 Nov 2018. 61(22):9841-9878.
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