ACCEPTING DOCTORAL STUDENTS
Dr. K.H. Lee combines the fields of the most advanced natural products chemistry and synthetic medicinal chemistry as well as cutting-edge life science technologies to design and discover herbal medicine-based bioactive natural products and their analogs as clinical trials drug candidates. Since 1971, his efforts have led to the discovery of several thousand such compounds, providing leads for new generation drug design to develop future pharmaceutical agents in the same manner that numerous previously discovered bioactive natural products (including taxol, ephedrine, and artemisinin) were developed as current pharmaceutical agents to treat cancers and other diseases. The lead compounds newly discovered by Dr. Lee’s research group will provide a solid foundation of potential chemotherapeutic drug candidates in the 21st century.
A summary of Dr. Lee’s accomplishments:
- 922 research articles in refereed journals
- 121 patents
- 456 invited lectures and presentations
- Serving as an editorial advisory board member for 29 journals
- Medicinal Chemistry
- Bioactive Natural Products
- New Anticancer and Anti-AIDS Drug Discovery and Development
- Chinese Medicine
- PG-2 was discovered and developed by Pharmagenesis and PhytoHealth Corporation of Taiwan based on the initial advice of Dr. Lee. It is composed of polysaccharide immunostimulatory principles from Astragalus membranaceus (Huang Qi). PG-2 was approved for clinical use in treating cancer-related fatigue by the Taiwan Department of Health in 4/2011, especially for cancer patients who developed severe fatigue after receiving chemotherapy. Application for the use of PG-2 from the US FDA is ongoing.
- Bevirimat (DSB, PA-457, MPC-4326), derived from natural triterpenes found in Syzigium claviflorum (Pang Hua Chih Nan), was licensed previously to Panacos Pharmaceuticals, Inc. and then to Myriad Pharmaceutical Company. It succeeded in Phase IIa anti-AIDS clinical trials and notably targets a different stage of the HIV virus compared with the current anti-AIDS drugs. Bevirimat is the first member of a completely new class of HIV drug candidates called “maturation inhibitors”. Research is very actively ongoing in the NPRL aimed at producing an improved candidate compound, without a partial drug-resistant problem encountered by bevirimat during its Phase IIb clinical trials.
- The 2-phenyl-4-quinolone analog CVM-1118 (formerly TRX-818 or CHM-2133-P), which is related to antileukemic natural flavonoids from Wikstroemia indica (Liao Ge Wang), showed excellent in vivo antitumor activity against ovarian cancer as a result of collaborative studies with Dr. Sheng-Chu Kuo of China Medical University, Taiwan. TaiRx, Inc., (formerly Effpha Corp.), Taiwan, has licensed this technology and is currently in Phase II anticancer clinical trial in the USA.
- JC-9 (or ASC-9), based on the natural product curcumin from Curcuma longa rhizome (Jiang Huang) was discovered and developed in the NPRL and licensed to AndroScience Corporation. JC-9 succeeded in a Phase II clinical trial against acne and is a clinical trial candidate for prostate and other cancers.
- GL-331, a synthetic analog of podophyllotoxin found in Podophyllum emodi (Gui Jiu), was discovered and developed in the NPRL with co-inventorship with Dr. Yung-Chi Cheng of Yale University. The product was licensed to Genelab Technologies Inc. of CA and reached Phase II clinical trial as an anticancer drug.
- 6. Neo-tanshinlactone, a natural product found in Salvia miltiorrhiza (Tanshen or Danshen), was newly discovered and synthesized by Dr. Lee’s group. Neo-tanshinlactone is more active and selective than tamoxifen, a currently used anti-breast cancer drug. Further syntheses and development of new analogs of neo-tanshinlactone as clinical trials candidates for treating breast cancer are ongoing.
- PBTs, novel phenanthrene-based tylophorine analogs discovered and synthesized by Dr. Lee’s group based on the natural alkaloid tylophorine isolated from Tylophora species, were found for the first time to inhibit lung cancer progression through the Slug signaling pathway resulting from a collaboration with Dr. Pan-Chyr Yang of National Taiwan University. This finding may offer a novel path of drug development to treat lung cancer.
- Preclinical studies on many other novel promising antiviral natural product-based leads are in progress. These include khellactone structural analogs (DCK) of the natural coumarin suksdorfin, which appears to inhibit HIV reverse transcriptase by a different mechanism from that of currently available non-nucleoside RT inhibitors. Experiments are ongoing to identify the specific molecular target. Certain structurally related pyranochromone analogs (DCP) have also shown excellent activity against both non-drug-resistant and drug-resistant HIV strains. In addition, development of novel anti-HIV diterpenes, including stelleralide A and gnidimacrin-related daphnane diterpenes to eliminate the latent HIV-1 are currently actively ongoing.
Awards and Honors
- First Lifu Academic Award for Chinese Medicine (1994)
- Academician of Academia Sinica (1996)
- Outstanding Achievement Award, University of Minnesota (1999)
- Taiwanese-American Foundation Achievement Award in Science and Engineering (2003)
- Kitasato Microbial of Chemistry Medal, Japan (2005)
- American Society of Pharmacology Norman R. Farnsworth Research Achievement Award (2009)
- Order of Rising Sun, Gold Rays with Neck Ribbon from the government of Japan (2011)
- China 100 Distinguished Alumni Award from University of Minnesota out of 10,000 Chinese Alumni (2014)
- Ernest H. Volwiler Research Achievement Award, American Association of College of Pharmacy (2015)
- Member, The Tang Prize in Biopharmaceutical Science Selection Committee, Academia Sinica (2014-2016)
- Third Cheung On Tak International Award for Outstanding Contribution to Chinese Medicine, Hong Kong Baptist University (2016)
Dr. Lee was also an elected fellow of the following associations:
- Fellow, American Association of Pharmaceutical Scientists (1986)
- Fellow, American Association for the Advancement of Science (1994)
- Fellow, American Society of Pharmacognosy (2010)
- Kaohsiung Medical University (Taiwan), BS, Pharmacy, 1961
- Kyoto University (Japan) MS, Pharmaceutical Chemistry, 1965
- University of Minnesota (Minneapolis), PhD, Medicinal Chemistry, 1968
- University of California (Los Angeles), Postdoctoral Scholar, Organic Chemistry, 1968-70