Shanghai Institute of Material Medical Chinese Academy of Sciences

Biography

Prof. Shen completed his undergraduate education at China Pharmaceutical University in 1995 and received a Ph.D. in Organic Chemistry at SIMM in 1998. He is now a Principal Investigator and Ph.D. student advisor at SIMM, CAS. He has also served as a scientific advisor to the pharmaceutical industry.

Among his drug discovery projects, four of the drug candidates are being under clinical trials. TPN729 and TPN171 are now in Phase II clinical trials in China for the indications of ED and PAH, respectively; TPN672, a 5-HT1A receptor agonist, is under Phase I for the indication of schizophrenia; TPN102 for epilepsy is also in Phase I study. The IND application for VV116, an orally administered anti-SARS-CoV-2 nucleoside drug candidate, was just submitted to NMPA in January 2021.

Dr. Shen has gained rich experience in industrial-oriented route design and organic process research & development. He strives for easier and safer operations, environmental friendly, cost effective, and IP free strategies, and eventually go with such robust technologies for translation and production in compliance with GMP.

Education

1995.09 - 1998.07 Ph.D. degree in Organic Chemistry, the Shanghai Institute of Materia Medica, Chinese Academy of Sciences

1992.09 - 1995.07 Master degree in Medicinal Chemistry, China Pharmaceutical University

Work Experience

2006-Present Professor and Principal Investigator, Department of Medicinal Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences

2001-2005 Associated Professor, Department of Medicinal Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences

1998-2000 Assistant Professor, Department of Medicinal Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences

Research Directions

1. New drug discovery and development for the treatments of diseases related to the central nervous system and infection.

2. Green and sustainable chemistry with a strategy of "control from root design": an industry-oriented innovation aimed to find a qualified route of synthesis from the very beginning of a project and then to establish a well optimized process to enable a safe, simple, cost effective and environmental friendly production of an active pharmaceutical ingredient.

Grants & Research Projects

Achievements

TPN729: has the characteristics of high activity and selectivity, good efficacy, low toxicity, and excellent pharmacokinetic properties. TP729 is expected to have fewer side effects in comparison with currently available PDE5 inhibitors. TPN729 and its tablets (25 mg and 50 mg) were approved by China Food and Drug Administration (CFDA, now NMPA) for clinical trials for ED in June, 2013, and is currently under phase II clinical trials.

TPN171: a selective PDE5 inhibitor with novel chemical structure. TPN171 exhibited excellent efficacy with very low dosage, high bioavailability, long terminal half-life, and good safety profile in preclinical research. The results of phase I clinical studies showed that TPN171 was well tolerated and had no significant effect on cardiovascular system and vision. The adverse reactions were mild and transient, mainly headache, dizziness, nasal congestion and flushing. TPN171 is currently under Phase II clinical trials for the treatment of PAH and ED.

TPN672: a multi-targeted drug candidate for schizophrenia acting as a dopamine 5-HT1A receptor agonist / D2 receptor partial antagonist / 5-HT2A receptor antagonist. TPN672 displayed robust antipsychotic efficacy, significantly higher than aripiprazole in rodent models (such as blocked phencyclidine-induced hyperactivity, and ameliorated negative symptoms and cognitive deficits in sociability test, dark avoidance response, Morris water maze test, and novel object recognition test). TPN672 also shows good pharmacokinetic properties, low side effects, high safety profile, and stable physicochemical properties. The phase Ia clinical trial has been completed, and a phase Ib clinical trial in patients with schizophrenia is in progress.

TPN102: a novel neurotherapeutic agent as a drug candidate for the treatment of epilepsy. In vivo pharmacodynamics study demonstrated that TPN102 significantly reduced the incidence of generalized tonic-clonic seizure, and showed superior efficacies in 6-Hz mouse model (therapy-resistant epilepsy model) and PTZ induced seizure mouse model than topiramate and zonisamide. TPN102 has high bioavailability, a good safety profile and stable physicochemical properties. The phase Ia clinical trial in healthy volunteers has been completed, and a phase Ib clinical trial in patients with epilepsy is in preparation.

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Social Titles

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Awards & Honors

Special government allowances of the State Council (Year 2019)

Jiangsu Innovative and entrepreneurial Talent (Year 2010)

Shanghai Talent Development Funds (Year 2008)

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Pubilcations

Full Publication List

Selected Publications

1.Melkamu AlemuAbame, Yang He, Song Wu, Zhifei Xie, Jian Zhang, Xudong Gong, Chunhui Wu*, Jingshan Shen*. Chronic administration of synthetic cannabidiol induces antidepressant effects involving modulation of serotonin and noradrenaline levels in the hippocampus. Neuroscience Letters, 2021, 744, 135594.

2.Zhen Wang1, Zhen Wang1, Xiangrui Jiang, Qingjie Zhao, Jingshan Shen*. Targeted Drugs for Treatment of Pulmonary Arterial Hypertension: Past, Present, and Future Perspectives. 2020, 63, 15153–15186.

3.Xudong Gong, Changliang Sun, Melkamu Alemu Abame, Wenqiang Shi, Yuanchao Xie, Wanbin Xu, Fuqiang Zhu, Yan Zhang, Jingshan Shen*, and Haji A. Aisa*.Synthesis of CBD and its derivatives bearing various C4’-side chains with a late-stage diversification method. J Org. Chem. 2020，85, 2704–2715.

4.Junchi Zhang, Yang He, Xiangrui Jiang, Hualiang Jiang*, Jingshan Shen*. Nature brings new avenues to the therapy of central nervous system diseases—An overview of possible treatments derived from natural products. Sci China Life Sci 2019, 62, 1332-1367.

5.Weiming Chen, Jin Suo, Yongjian Liu, Yuanchao Xie, Mingjun Wu, Fuqiang Zhu, Yefeng Nian, Haji A. Aisa* and Jingshan Shen*. Industy-Oriented Route Evaluation and Process Optimization for the Preparation of Brexpiprazole. Org. Process Res. Dev. 2019, 23, 852-857

6.Zhen Wang, Xiangrui Jiang, Xianglei Zhang,Guanghui Tian, Rulei Yang, Jianzhong Wu, Xiaoli Zhou, Zheng Liu, Xiaojun Yang, Chunhui Wu, Jing Shi, Jianfang Li, Jin Suo, Yu Wang, Rongxia Zhang, Zhijian Xu, Xudong Gong, Yang He, Weiliang Zhu, Haji Akber Aisa, Huangliang Jiang, Yechun Xu, and Jingshan Shen*. Pharmacokinetic-driven optimization of 4(3H)-pyrimidiones as phosphodiesterase Type 5 inhibitiors leading to TPN171, a clinical candidate for the treatment of pulmonary arterial hypertension. J. Med. Chem. 2019 62, 4979-4990

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