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Our laboratory is engaged in medicinal chemistry and chemical biology. We dedicated to the discovery and development of agents of medicinal value. We are working in two main areas:

(1) Total Synthesis and Biological Evaluation of Natural Products and Their Analogues.

Natural products have provided considerable value to the pharmaceutical industry over the past half-century. In particular, the therapeutic area of oncology has benefited from numerous drug classes derived from natural product sources. In fact, over 60% of the anticancer agents approved recently have been of natural origin. Chemical synthesis of natural products and their analogues has been a key tool in drug discovery and development. The synthesis allows verification of primary structure proposed on the basis of studies of natural product, and presents opportunities to modify the structure, with the ultimate aim of improving activity or physicochemical/biological properties of the lead molecule. Synthesis is also crucial in the establishment of structure-activity relationships since the ability to make analogues of the lead compound chemically is a prerequisite of drug discovery. We have been particularly devoting to the exploration of natural-products-based novel antitumor agents. The larger part of our research program is dedicated to the training and research in synthesis and biological evaluation of natural products with known anticancer activities.

(2) Design and Syntheses of Novel Small Molecule Bioprobes and Drugs.

In the second area, my research centers on rationally designed molecular probes and their application to biological problems, especially in cancer biology and neurodegenerative disorders. Protein–protein interactions play a key role in most biological processes, and offer attractive opportunities for therapeutic intervention. The targeted manipulation of protein-protein interactions with the use of small molecules is rapidly gaining importance in the development of biological tools for dissecting living processes on a molecular level and for the discovery of conceptually novel drugs. We have been focusing on the discovery of small molecules/peptidomimetics to prevent the degradation of p27, p53 and to regulate histone methylation process and epigenetic control.

The rigid coil RNLFGP motif of p27 binds a shallow cyclin-A groove Surrogate binds with the cyclin-A groove (salmon)

The structure of PIP-box peptide binding with PCNA The interactions between PIP-m41 & PCNA

O-Bridged Helix mimetic binding with PCNA The interactions between the substrate-like peptide inhibitors and LSD1 The interactions between de novo designed small molecule inhibitors and LSD1

(3) Structural- and/or functional- diversity oriented methodology development.

Despite rapid advances in synthetic organic chemistry, many intriguing small molecules remain inefficient to access via traditional methods. By combining the power of modern transition metal catalysis, enzymatic tools and advances in photocatalysis, our laboratory develops practical solutions for conventionally challenging organic transformations, aiming to deliver diverse novel structures and functions to chemical society. The identification and realization of powerfully simplifying transformations, which allow for rapid and efficient inroads into the target structure, is one of the major motivations for our research program.