Establishment and Development:

Our laboratory initially focused on medicinal chemistry research, with a specific emphasis on drug design, synthesis, and biological evaluation targeting epigenetic drug targets such as HDAC and the anti-apoptotic protein Bcl-2. Over the past decades, we have integrated computer-aided drug design techniques into our research, such as virtual screening, which assists us in rapidly identifying bioactive lead compounds. In recent years, we have expanded our research to new targets, such as protein tyrosine phosphatase. Additionally, we have conducted chemical biology studies to gain a deeper understanding of the biological functions of target proteins.

Team Members:

Our research team consists of senior medicinal chemists, as well as young researchers specializing in computer-aided drug design, peptide chemistry, biomaterials, and other related research areas.

Research Areas:

1. Structure-based drug design, synthesis, and chemical biology research.

2. Computer-aided drug design and virtual screening.

3. Development of novel methods for peptide synthesis.

4. Design and application of biocompatible materials.

    

Research Achievements:

We have made significant contributions in the field of HDAC inhibitors. Through the structure optimization of lead compounds, we have successfully identified selective HDAC inhibitors. Moreover, we have also designed dual-target inhibitors of proteasome/HDAC that have demonstrated excellent anti-tumor activity against bortezomib-resistant multiple myeloma. Additionally, our designed HDAC-Bax dual-functional compounds have shown improved anti-tumor potency against solid tumors by more effectively activating apoptosis. Most recently, we have developed DNA-targeted HDAC inhibitors and SHP2/HDAC dual-target inhibitors, which exert anti-tumor effects through a dual mechanism involving cytotoxicity and tumor immune activation.

Main Publications:

1. Chen C, Li X, Zhao H, Liu M, Du J, Zhang J, Yang X, Hou X*, Fang H*. Discovery of DNA-Targeting HDAC Inhibitors with Potent Antitumor Efficacy In Vivo That Trigger Antitumor Immunity. J. Med. Chem.2022, 65(4):3667-3683.

2. Liu M, Gao S, Liang T, Qiu X, Yang X, Fang H*, Hou X*. Discovery of Novel Src Homology-2 Domain-Containing Phosphatase 2 and Histone Deacetylase Dual Inhibitors with Potent Antitumor Efficacy and Enhanced Antitumor Immunity. J. Med. Chem. 2022, 65(18):12200-12218.

3. Liu M, Gao S, Elhassan RM, Hou X*,Fang H*. Strategies to overcome drug resistance using SHP2 inhibitors. Acta Pharm. Sin. B.2021, 11(12):3908-3924.

4. Elhassan RM, Hou X*,Fang H*. Recent advances in the development of allosteric protein tyrosine phosphatase inhibitors for drug discovery. Med. Res. Rev.2022, 42(3):1064-1110.

5. Liang T, Zhou Y, Elhassan RM, Hou X, Yang X, Fang H*. HDAC-Bax Multiple Ligands Enhance Bax-Dependent Apoptosis in HeLa Cells. J. Med. Chem., 2020, 63(20):12083-12099.

6. Zhou Y, Liu X, Xue J, Liu L, Liang T, Li W, Yang X, Hou X, Fang H*. Discovery of Peptide Boronate Derivatives as Histone Deacetylase and Proteasome Dual Inhibitors for Overcoming Bortezomib Resistance of Multiple Myeloma. J. Med. Chem.,2020, 63, 4701-4715.

7. Liang T, Xue J, Yao Z, Ye Y, Yang X, Hou X, Fang H. Design, synthesis and biological evaluation of 3, 4-disubstituted-imidazolidine-2, 5-dione derivatives as HDAC6 selective inhibitors.Eur. J. Med. Chem., 2021, 221, 113526.

8. Hou X, Sun J-P, Ge L, Liang X, Li K, Zhang Y, Fang H*. Inhibition of Striatal-enriched Protein Tyrosine Phosphatase by Targeting Computationally Revealed Cryptic Pockets. Eur. J. Med. Chem.,2020, 190, 112131.

9. Liu L, Liu R, Yang X, Hou X*, Fang H*. Design, synthesis and biological evaluation of tyrosine derivatives as Mcl-1 inhibitors. Eur. J. Med. Chem.2020, 191, 112142.

10. Liang T, Hou X, Zhou Y, Yang X, Fang H*. Design, Synthesis, and Biological Evaluation of 2,4-Imidazolinedione Derivatives as HDAC6 Isoform-Selective Inhibitors. ACS Med. Chem. Lett.2019, 10, 1122-1127.

Facilities & Resources:

Our state-of-the-art facilities and cutting-edge technology enable us to conduct research that is both rigorous and innovative. In addition to the equipment available at the Shandong University Public Instrument Platform, our research group also has 2 rapid preparative liquid chromatography systems, a polarimeter, a freeze dryer, a high-speed centrifuge, an enzyme marker, and other equipment.

Collaborations & Partnerships:

Our collaborators include Professor Yingkai Zhang from New York University and Professor Weiping Tang from the University of Wisconsin-Madison.

Recreational Activities:

Jinan City is a famous historical and cultural city in China. Our research group utilizes spare time to organize team activities such as hiking and mountain climbing.

Other Features:

The distinctive feature of our research group is the deep integration of medicinal chemistry and computer-aided drug design, enabling accurate and rapid discovery of lead compounds and rational structure optimization, significantly enhancing research efficiency.

Contact:

For more information or inquiries, please contact us at haofangcn@sdu.edu.cn