Professor
Research Areas
Medicinal Chemistry
Education & Positions
Beijing Medical University, Postdoctoral Fellow, 1991-1993 Beijing Medical University, Associate Professor, 1994-2012
School of Pharmaceutical Sciences, Peking University, Professor, 2012- Visiting Scientist, School of Pharmacy, University of California at San Francisco; College of Pharmacy, University of Michigan, 1998-2000
Visiting Professor, School of Pharmacy, Kyushu University, 2007.1-2007.2
Visiting Professor, School of Pharmacy, Howard University, 2014.2-2014.3
Director, Department of Medicinal Chemistry, Peking University, 2002-
Vice Dean, School of Pharmaceutical Sciences, Peking University, 2004-2009
Faculty Accolades
The Second Class Prize of State Natural Science Prize, 2004
The Second Class of Excellent Achievement Award for Scientific Research in Colleges and Universities, 2009
Research Interests
Our research covers a broad range of medicinal chemistry, chemical biology, computer-aided drug design. Cyclic ADP-ribose (cADPR) regulated calcium signaling pathway has been associated with a variety of cellular processes. To investigate whether cADPR elicits Ca2+ release by direct binding to RyR or via an associated protein, we designed a photo-affinity probe based on the SAR studies, and set up an approach to fish and validate the binding protein of cADPR. The result clearly indicated that GAPDH is the long-sought-after cADPR binding protein and is required for cADPR-mediated Ca2+ mobilization from ER via RyRs. Computer-aided drug design (CADD) is widely used for the discovery of bioactive molecules. We have set up a comprehensive CADD platform and developed methodologies to design molecules, such as maximal unbiased benchmarking data set for virtual screening, deep learning based de novo drug design, data mining in drug-target-disease network, and so on. In addition, the above developed approaches are applied to discover and optimize drug candidates targeted to several important diseases related biomolecules, such as mTOR, dopamine receptor, TRPM2,a7-nAChR, CD38, etc.
Grants and Fundings
1. National Natural Science Foundation of China (NSFC), STUDIES ON THE DESIGN, SYNTHESIS AND BIOLOGICAL FUNCTION OF THE INHIBITORS OF GAPDH
Principle Investigator
2. National Natural Science Foundation of China (NSFC), DISCOVERY OF NOVEL AGONISTS OF a-7 NICOTINIC ACETYLCHOLINE RECEPTORS AND INVESTIGATION ON THEIR BIOLOGICAL FUNCTIONS
Principle Investigator
3. National Natural Science Foundation of China (NSFC), INVESTIGATION OF THE NUCLEIC ACID RELATED SIGNALING PATHWAY REGALATED BY LIGANDS
Principle Investigator
4. National Natural Science Foundation of China (NSFC), STUDIES ON THE DESIGN, SYNTHESIS AND BIOLOGICAL FUNCTION OF CALCIUM SIGNALING RELATED MULTI-FUNCTIONAL ENZYME (CD38)
Principle Investigator
5. National Major Scientific and Technological Special Project for “Significant New Drugs Development”, PRECLINICAL STUDIES ON THE NOVL ANTI-SCHIZOPHRENIA DRUG
Principle Investigator
Publications(2014-2018):
1. Wang, X.; Zhang, X.; Zhang, K.; Hu, J.; Liu, Z.; Jin, H.*; Zhang, L.*; Zhang, L.-H. Calcium mobilizing behaviors of neutral cyclic ADP-ribose mimics which integrate the modifications of nucleobase, northern ribose and pyrophosphate. ChemBioChem 2018, DOI: 10.1002/cbic.201800133.
2. Zhang, H.; Liu, H.; Luo, X.; Wang, Y.; Liu, Y.; Jin, H.; Liu, Z.; Yang, W.; Yu*, P.; Zhang, L.*; Zhang, L.-H. Design, synthesis and biological activities of 2,3-dihydroquinazolin-4(1H)-one derivatives as TRPM2 inhibitors. Eur J Med Chem 2018, 152, 235-252.
3. Xia, J.; Reid, T.-E.; Wu, S.; Zhang, L.*; Wang, X.* Maximal Unbiased Benchmarking Data Sets for Human Chemokine Receptors and Its Comparative Analysis. J Chem Inf Modeling, 2018, 58, 1104-1120.
4. Zhang, K.; Sun, W.; Huang, L.; Zhu, K.; Zhu, L.; Wang, Q.; Lu, Y.; Zhang, H.; Jin, H.; Zhang, L.-H.*; Zhang, L.*; Yue, J.* Identifying GAPDH as a Novel Cyclic Adenosine Diphosphoribose (cADPR) Binding Protein by Photoaffinity Protein-Ligand Labeling Approach. J Am Chem Soc 2017, 139, 156-170.
5. Mao, B.; Gao, S.; Weng, Y.; Zhang, L.*; Zhang, L.-H. Design, synthesis, and biological evaluation of imidazo[1,2-b]pyridazine derivatives as mTOR inhibitors. Eur J Med Chem 2017, 129, 135-150.
6. Xue, Y.; Tang, J.; Ma, X.; Li, Q.; Xie, B.; Hao, Y.; Jin, H.; Wang, K.*; Zhang, G.; Zhang, L.*; Zhang, L.-H. Synthesis and Biological Activities of Indolizine derivatives as Alpha-7 nAChR Agonists. Eur J Med Chem 2016, 115, 94-108.
7. Xia, J.; Tilahun, E.; Kebede, E.; Reid, T.-E.; Zhang, L.*; Wang, X.* Comparative Modeling and Benchmarking Data Sets for Human Histone Deacetylases and Sirtuin Families. J Chem Inf Modeling, 2015, 55(2), 374-388.
8. Xia, J.; Jin, H.; Liu, Z.; Zhang, L.*; Wang X. S.* An Unbiased Method to Build Benchmarking Sets for Ligand-Based Virtual Screening and its Application to GPCRs. J Chem Inf Modeling, 2014, 54, 1433-1450.
