My research interests are broadly based on the interface of synthetic
organic chemistry and medicinal chemistry, and in particular on the drug
discovery of bioactive molecules to probe biological systems or act as
potential therapeutic agents in neuroscience and oncology. With this
general idea in mind, and in active collaboration with other biologists
and pharmacologists, my group would like to establish as strong and
creative research program that applies state-of-the-art chemical
approaches to biological problems impacting diagnosis, prevention and
treatment of human diseases.
One of our current efforts is focused on design and synthesis of small
molecules for probing function and development of pharmacological tools
for understanding the workings of the brain and that of novel therapies
for central nervous system (CNS) disorders such as drug abuse and
addiction, depression, schizophrenia, pain, and neurodegenerative
diseases. The proposed projects in this area include the
identification, characterization and optimization of allosteric
modulators, bitopic ligands, and inverse agonists of 5-HT2C
receptor,neuromedin U receptor 2 (NMUR2) ligands, as well as AMPA
receptor positive allosteric modulators for preventing neuroapoptosis.
We are also working on the discovery of DeltaFosB inhibitors, neurexin
modulators, and FG14/Nav1.6 channel complex inhibitors as CNS probes and
potential therapeutics. Another line of research development centers
on the establishment of novel chemical libraries aiming at
mechanism-based or lead compound-based cancer drug discovery,
particularly by targeting Bcl-2 family proteins and apoptosis pathways
as well as novel transcription factors. The molecular targets of our
drug design include, but are not limited to, the activator protein 1
(AP-1), Krueppel-like factor 5 (KLF5), KRAS, signal transducers and
activators of transcription (STATs) with the aid of molecular docking.
Specifically, we are developing Bax activators, BH4 domain antagonists
of Bcl2, orally bioavailable STAT3 inhibitors, AP-1 inhibitors, KLF5
inhibitors, KRAS plasma membrane localization inhibitors,
cystathionine-β-synthase (CBS) inhibitors as a new class of
preventative/therapeutic agents for various human cancers including
brain tumors, breast cancer, lung cancer, head/neck cancer, colorectal
cancer, prostate cancer, and pancreatic cancer as well as inflammation.
Other research efforts include design and synthesis of small molecule
probes targeting EPAC, which are exchange factors. Last but not least,
we are also working on natural product-inspired diversity-oriented
synthesis that may lead to exciting potentials for novel small molecule
drug discovery.