Research Areas and interesting

Medicinal Chemistry and Molecular Design

Pharmaceutical Informatics

Education & Positions

Peking University Health Sciences Center (PKU-SC), B.S., 2000

Peking University, Ph.D., 2005

Peking University Health Sciences Center (PKU-SC), Assistant Professor 2002-2011

Project officer, China National Center for Biotechnology Development (CNCBD), Ministry of Science and Technology of the People's Republic of China 2007-2009

FFCSA, Postdoctoral Fellow, 2009-2011

Peking University Health Sciences Center (PKU-SC), Associate Professor 2011-

Project officer, Develpmengt Center for Medical Science and Technology (DCMST), National Health and Family Planning Commission of the People's Republic of China 2015-2017

Project officer, National Science and Technology Major Projects for "Major New Drugs Innovation and Development" Special office, National Health and Family Planning Commission of the People's Republic of China 2015-2017

Faculty Accolades

1. Prominent teacher of Peking University (2014)

2. Prominent teacher of Peking University (2009)

3. Prominent teacher of Peking University (2007)

4. The CPA-Servier Young Investigator Awards in Medicinal Chemistry by Chinese Pharmaceutical Association (2006)

Research Interests

Our research is focused on developing new drug/ molecular design methods that are relevant to the lead discovery and applying them in the medicinal potential developing of newly synthesized natural products and analogs thereof.

Grants and fundings

1. Beijing Municipal Natural Science Foundation (7202088): Design, synthesis and anti-tumor activity evaluation of specific inhibitors of Signal Transducer and Activator of Transcription 3 (STAT3). 2020.1-2022.12

2. The National Key Research and Development Program of China (2019YFC1708902): Exploring the direct targets of Traditional Chinese Medicine: Discovery, validation and investigation of related pathway regulation, 2019.12-2021.12

3. Technical Service entrusted by Beijing Tide Pharmaceutical Co.,Ltd. (20190644): Design and development of novel targeted agents, 2019.10-2020.10.

4. The National Natural Science Foundation of China (NSFC, 21772005): Design, synthesis and biological evaluation of novel potent specific inhibitors of Ataxia-Telangiectasia Mutant (ATM) Kinase. 2018.1-2021.12

5. The National Natural Science Foundation of China (NSFC, 2157020178): Structure-based design, synthesis and discovery of potent specific endothelial lipase (EL) inhibitors. 2016.1-2019.12

6. The National Natural Science Foundation of China (NSFC, 21272017): Design, synthesis and biological evaluation of non-covalent CD38 inhibitors. 2013.1-2016.12

7. The National High Technology Research and Development Program of China (863 program, 2012AA020308): Techniques for drug target discovery and drug molecular design. 2012.1-2015.12

8. The National Natural Science Foundation of China (NSFC, 20802006): Design, synthesis and biological evaluation of CD38 inhibitors. 2009.1-2011.12

9. The National High Technology Research and Development Program of China (863 program, 2006AA020403): Disease target prediction and analysis system, 2007.1-2010.12

Publications

1. Chuanyu Lyu, Tong Chen, Bo Qiang, Ningfeng Liu, Heyu Wang, Liangren Zhang, Zhenming Liu*, CMNPD: a comprehensive marine natural products database towards facilitating drug discovery from the ocean, Nucleic Acids Research, 2020 Sept 28; gkaa763. doi: 10.1093/nar/gkaa763.

2. Zhang H, He X, Wang X, Yu B, Zhao S, Jiao P, Jin H, Liu Z*, Wang K, Zhang L, Zhang L. Design, synthesis and biological activities of piperidine-spirooxadiazole derivatives as α7 nicotinic receptor antagonists. Eur J Med Chem. 2020 Aug 22; 207:112774. doi: 10.1016/j.ejmech.2020.112774. 

3. Jiao P, Wang Y, Mao B, Wang B, Zhong Y, Jin H, Zhang L, Zhang L, Liu Z*. Discovery of 2-(2-aminobenzo[d]thiazol-6-yl) benzo[d]oxazol-5-amine derivatives that regulated HPV relevant cellular pathway and prevented cervical cancer from abnormal proliferation. Eur J Med Chem. 2020 Oct 15; 204:112556. doi: 10.1016/j.ejmech.2020.112556. 

4. Lai J, Hu J, Wang Y, Zhou X, Li Y, Zhang L, Liu Z*. Privileged Scaffold Analysis of Natural Products with Deep Learning-based Indication Prediction Model. Mol Inform. 2020 May 14. doi: 10.1002/minf.202000057. 

5. Wang Y, Hu J, Lai J, Li Y, Jin H, Zhang L, Zhang LR, Liu ZM*. TF3P: Three-Dimensional Force Fields Fingerprint Learned by Deep Capsular Network. J Chem Inf Model. 2020 Jun 22; 60(6): 2754-2765. doi: 10.1021/acs.jcim.0c00005.

6. Zou Y, Hu J, Jie J, Lai J, Li M, Liu Z*, Zou X. Comprehensive analysis of human IgG Fc N-glycopeptides and construction of a screening model for colorectal cancer. J Proteomics. 2020 Feb 20; 213:103616. doi: 10.1016/j.jprot.2019.103616.

7. Li Y, Hu J, Wang Y, Zhou J, Zhang L, Liu Z*. DeepScaffold: A Comprehensive Tool for Scaffold-Based De Novo Drug Discovery Using Deep Learning. J Chem Inf Model. 2020 Jan 27; 60(1): 77-91. doi: 10.1021/acs.jcim.9b00727. 

8. Xu HY; Zhang YQ; Liu ZM#; Chen T; Lv CY; Tang SH; Zhang XB; Zhang W; Li ZY; Zhou RR;Yang HJ; Wang XJ; Huang LQ. ETCM: an encyclopaedia of traditional Chinese medicine. Nucleic Acids Research. 2019. 47(D1): D976-D982. doi: 10.1093/nar/gky987.

9. Yu P, Liu Z#, Yu X, Ye P, Liu H, Xue X, Yang L, Li Z, Wu Y, Fang C, Zhao YJ, Yang F, Luo JH, Jiang LH, Zhang L, Zhang L, Yang W. Direct Gating of the TRPM2 Channel by cADPR via Specific Interactions with the ADPR Binding Pocket. Cell Rep. 2019 Jun 18; 27(12): 3684-3695.e4. doi: 10.1016/j.celrep.2019.05.067. 

10. Yang L, Liu Y, Fan M, Zhu G, Jin H, Liang J, Liu Z*, Huang Z, Zhang L. Identification and characterization of benzo[d]oxazol-2(3H)-one derivatives as the first potent and selective small-molecule inhibitors of chromodomain protein CDYL. Eur J Med Chem. 2019 Nov 15; 182: 111656. doi: 10.1016/j.ejmech.2019.111656. 

11. Xue Y, He X, Yang T, Wang Y, Liu Z*, Zhang G, Wang Y, Wang K, Zhang L, Zhang L. Discovery of fused heterocyclic carboxamide derivatives as novel α7-nAChR agonists: Synthesis, preliminary SAR and biological evaluation. Eur J Med Chem. 2019 Nov 15;182:111618. doi: 10.1016/j.ejmech.2019.111618. 

12. Dou X, Huang H, Li Y, Jiang L, Wang Y, Jin H, Jiao N, Zhang L, Zhang L, Liu Z*. Multistage Screening Reveals 3-Substituted Indolin-2-one Derivatives as Novel and Isoform-Selective c-Jun N-terminal Kinase 3 (JNK3) Inhibitors: Implications to Drug Discovery for Potential Treatment of Neurodegenerative Diseases. J Med Chem. 2019 Jul 25; 62(14): 6645-6664. doi: 10.1021/acs.jmedchem.9b00537.

13. Yang L, Li T, Li S, Wu Y, Shi X, Jin H, Liu Z*, Zhao Y, Zhang L, Lee HC, Zhang L. Rational Design and Identification of Small-Molecule Allosteric Inhibitors of CD38. Chembiochem. 2019 Oct 1; 20(19): 2485-2493. doi: 10.1002/cbic.201900169.

14. Wang Y, Dou X, Jiang L, Jin H, Zhang L, Zhang L, Liu Z*. Discovery of novel glycogen synthase kinase-3α inhibitors: Structure-based virtual screening, preliminary SAR and biological evaluation for treatment of acute myeloid leukemia. Eur J Med Chem. 2019 Jun 1; 171: 221-234. doi: 10.1016/j.ejmech.2019.03.039.

15. Li Y, Zhang L, Liu Z*. Multi-objective de novo drug design with conditional graph generative model. J Cheminform. 2018 Jul 24; 10(1):33. doi: 10.1186/s13321-018-0287-6.

16. Zhang H, Liu H, Luo X, Wang Y, Liu Y, Jin H, Liu Z*, Yang W, Yu P, Zhang L, Zhang L. Design, synthesis and biological activities of 2,3-dihydroquinazolin-4(1H)-one derivatives as TRPM2 inhibitors. Eur J Med Chem. 2018 May 25; 152:235-252. doi: 10.1016/j.ejmech.2018.04.045. 

17. Chen Y, Tang Y, Mao B, Li W, Jin H, Zhang L, Liu Z*. Discovery of N-(Naphtho[1,2-b]Furan-5-Yl) Benzenesulfonamides as Novel Selective Inhibitors of Triple-Negative Breast Cancer (TNBC). Molecules. 2018 Mar 16; 23(3). pii: E678. doi: 10.3390/molecules23030678

18. Dou X,Jiang L,Wang Y,Jin H,Liu Z*,Zhang L*. Discovery of new GSK-3β inhibitors through structure-based virtual screening. Bioorg Med Chem Lett.2018 Jan 15; 28(2):160-166.

19. Wang X, Zhang X, Zhang K, Hu J, Liu Z, Jin H, Zhang L, Zhang L. Calcium-Mobilizing Behaviors of Neutral Cyclic ADP-Ribose Mimics that Integrate Modifications to the Nucleobase, Northern Ribose and Pyrophosphate. Chembiochem. 2018 Jul 4; 19(13):1444-1451. doi: 10.1002/cbic.201800133.

20. Fan N, Zhang S, Sheng T, Zhao L, Liu Z*, Liu J, Wang X*. Docking Field-based QSAR and pharmacophore studies on the substituted pyrimidine derivatives targeting HIV-1 reverse transcriptase. Chem Biol Drug Des. 2017 Aug 17. doi: 10.1111/cbdd.13086. 

21. Luo Q, Zhao L, Hu J, Jin H, Liu Z*, Zhang L. The scoring bias in reverse docking and the score normalization strategy to improve success rate of target fishing. PLoS One. 2017 Feb 14; 12(2):e0171433. doi: 10.1371. 

22. Yang R, Zhang Y, Huang D, Luo X, Zhang L, Zhu X, Zhang X, Liu Z*, Han JY, Xiong JW*.Miconazole protects blood vessels from MMP9-dependent rupture and hemorrhage. Dis Model Mech. 2017 Mar 1;10(3):337-348. 

23. Yu P, Xue X, Zhang J, Hu X, Wu Y, Jiang LH, Jin H, Luo J, Zhang L, Liu Z*, Yang W*. Identification of the ADPR binding pocket in the NUDT9 homology domain of TRPM2. J Gen Physiol. 2017 Feb;149(2):219-235 

24. Wang Z, Niimi M, Ding Q, Liu Z, Wang L, Zhang J, Xu J, Fan J. Comparative studies of three cholesteryl ester transfer proteins and their interactions with known inhibitors. PLoS One. 2017 Aug 2; 12(8):e0180772. doi: 10.1371/journal.pone.0180772. 

25. Wang Y, Wu X, Du M, Chen X, Ning X, Chen H, Wang S, Liu J, Liu Z, Li R, Fu G, Wang C, McNutt MA, Zhou D, Yin Y. Eg5 inhibitor YL001 induces mitotic arrest and inhibits tumor proliferation. Oncotarget. 2017 Jun 27; 8(26):42510-42524. doi: 10.18632/oncotarget.17207

26. Han X, Zhong Y, Zhou G, Qi H, Li S, Ding Q, Liu Z, Song Y, Qiao X. Synthesis and biological evaluation of N-(carbobenzyloxy)-l-phenylalanine and N-(carbobenzyloxy)-l-aspartic acid-β-benzyl ester derivatives as potent topoisomerase IIα inhibitors. Bioorg Med Chem. 2017 Jun 15; 25(12):3116-3126. doi: 10.1016/j.bmc.2017.03.065. 

27. Li Y, Kong Y, Zhang M, Yan A, Liu Z. Using Support Vector Machine (SVM) for Classification of Selectivity of H1N1 Neuraminidase Inhibitors. Mol Inform. 2016 Apr; 35(3-4):116-24. doi: 10.1002/minf.201500107

28. Guo J, Ma X, Cai Y, Ma Y, Zhan Z, Zhou YJ, Liu W, Guan M, Yang J, Cui G, Kang L, Yang L, Shen Y, Tang J, Lin H, Ma X, Jin B, Liu Z, Peters RJ, Zhao ZK, Huang L. Cytochrome P450 promiscuity leads to a bifurcating biosynthetic pathway for tanshinones. New Phytol. 2016 Apr; 210(2):525-34. doi: 10.1111/nph.13790.

29. Wu S, Yin Q, Zhao L, Fan N, Tang X, Zhao J, Sheng T, Guo Y, Tian C, Zhang Z, Xu W, Liu Z, Jiang S, Ma L, Liu J, Wang X. A stereo configuration-activity study of 3-iodo-4-(2-methylcyclohexyloxy)-6-phenethylpyridin-2(2H)-ones as potency inhibitors of HIV-1 variants. Org Biomol Chem. 2016 Jan 28; 14(4):1413-20. doi: 10.1039/c5ob02154e. 

30. Zhang Y, Liu B, Wu X, Li R, Ning X, Liu Y, Liu Z, Ge Z, Li R, Yin Y. New pyridin-3-ylmethyl carbamodithioic esters activate pyruvate kinase M2 and potential anticancer lead compounds. Bioorg Med Chem. 2015 Aug 1; 23(15):4815-23. doi: 10.1016/j.bmc.2015.05.041.

31. Zhang S, Xue X, Zhang L, Zhang L, Liu Z*. Comparative Analysis of Pharmacophore Features and Quantitative Structure–Activity Relationships for CD38 Covalent and Non-covalent Inhibitors. Chem Biol Drug Des. 2015 Dec; 86(6):1411-24. doi: 10.1111/cbdd.12606.

32. Zeng L, Guan M, Jin H, Liu Z*, Zhang L. Integrating Pharmacophore into Membrane Molecular Dynamics Simulations to Improve Homology Modeling of G Protein-coupled Receptors with Ligand Selectivity: A2A Adenosine Receptor as an Example. Chem Biol Drug Des. 2015 Dec; 86(6):1438-50. doi: 10.1111/cbdd.12607. 

33. Pei F, Jin H, Zhou X, Xia J, Sun L, Liu Z, Zhang L. Enrichment Assessment of Multiple Virtual Screening Strategies for Toll-Like Receptor 8 Agonists Based on a Maximal Unbiased Benchmarking Data Set. Chem Biol Drug Des. 2015 Nov; 86(5):1226-41. doi: 10.1111/cbdd.12590.

34. Yang R, Yan S, Zhu X, Li CY, Liu Z*, Xiong JW*. Antimalarial drug artemisinin depletes erythrocytes by activating apoptotic pathways in zebrafish. Exp Hematol. 2015 Apr; 43(4):331-41.e8. doi: 10.1016/j.exphem.2014.11.012.

35. Xia J, Jin H, Liu Z, Zhang L, Wang XS. An Unbiased Method To Build Benchmarking Sets for Ligand-Based Virtual Screening and its Application To GPCRs. J Chem Inf Model. 2014 May 27; 54(5):1433-50. doi: 10.1021/ci500062f. 

36. Sun L, Jin H, Zhao X, Liu Z, Guan Y, Yang Z, Zhang L, Zhang L. Unfolding and Conformational Variations of ThrombinBinding DNA Aptamers: Synthesis, Circular Dichroism and Molecular Dynamics Simulations. ChemMedChem. 2014 May; 9(5):993-1001. doi: 10.1002/cmdc.201300564.

37. Wang Z, Li S, Sun L, Fan J, Liu Z*. Comparative Analyses of Lipoprotein Lipase, Hepatic Lipase, and Endothelial Lipase, and Their Binding Properties with Known Inhibitors. PLoS One. 2013 Aug 21; 8(8):e72146. doi: 10.1371/journal.pone.0072146.

38. Sun L, Tian F, Feng B, Liu Z, Zhang L, Pei J. Computational Identification of a New Binding Site in Influenza Virus Hemagglutinin for Membrane Fusion Inhibitors. Chem Biol Drug Des. 2013 Sep; 82(3):267-74. doi: 10.1111/cbdd.12156. 

39. Liu, Z., Graeff, R. M., Jin, H., Zhang, L., Zhang, L. Studies on CD38 Inhibitors and Their Application to cADPR-Mediated Ca2+ Signaling. MESSENGER 2013, Vol. 2, 1-14.

40. Huang W, Zuo T, Luo X, Jin H, Liu Z, Yang Z, Yu X, Zhang L, Zhang L. Indolizine Derivatives as HIV-1 VIFElonginC Interaction Inhibitors. Chem Biol Drug Des. 2013 Jun; 81(6):730-41. doi: 10.1111/cbdd.12119.

41. Huang W, Zuo T, Jin H, Liu Z, Yang Z, Yu X, Zhang L, Zhang L. Design, synthesis and biological evaluation of indolizine derivatives as HIV-1 VIF-ElonginC interaction inhibitors. Mol Divers. 2013 May; 17(2):221-43. doi: 10.1007/s11030-013-9424-3. 

42. Liu Z, Li B, Li X, Zhang L, Lai L. Identification of small-molecule inhibitors against human leukocyte antigen-death receptor 4 (HLA-DR4) through a comprehensive strategy. J Chem Inf Model. 2011 Feb 28; 51(2):326-34. doi: 10.1021/ci100444c. 

43. Li B, Liu Z*, Zhang L, Zhang L. Multiple-docking and affinity fingerprint methods for protein classification and inhibitors selection. J Chem Inf Model. 2009 Jul; 49(7):1725-33. doi: 10.1021/ci900044j.

44. Liu Z, Huang C, Fan K, Wei P, Chen H, Liu S, Pei J, Shi L, Li B, Yang K, Liu Y, Lai L. Virtual screening of novel noncovalent inhibitors for SARS-CoV 3C-like proteinase. J Chem Inf Model. 2005 Jan-Feb; 45(1):10-17.