A Set of Small Molecule Inhibitors of Human Galactokinase (GALK)
Kent Lai, Klaas Wierenga and Manshu Tang
Problem
Classic Galactosemia is a potentially lethal disorder caused by the deficiency of galactose 1-phosphate uridyltransferase. The only treatment for galactosemia is eliminating lactose and galactose from the diet. Even with an early diagnosis and a restricted diet, however, many individuals with galactosemia experience long-term complications such as mental and growth retardation, speech difficulties, premature ovarian failure, and neurological impairment. Thus, a more effective treatment is urgently needed.
Solution
It is generally accepted by the medical community that galactose 1-phosphate, the product of the human enzyme galactokinase (GALK), plays a major role in the pathogenesis of Classic Galactosemia. Thus, the inventors have generated a high-throughput screening assay to identify small molecule inhibitors of human galactokinase (GALK). Using this approach, they have found a set of 34 small molecules that specifically inhibit GALK with high potency.
Competitive Advantage
Primary Opportunity: Novel and
effective treatment for Classic Galactosemia will qualify as Orphan
Drug according to the US Federal Orphan Drug Act (Amended);
Expanded Opportunities: CDP-ME kinase, a member of the GHMP
kinase superfamily, is an essential enzyme present exclusively in
many pathogenic bacteria, chlamydia, and protozoa. Therefore, novel
inhibitors for this unique enzyme can target these pathogens with
minimal side-effects on the infected human patients and animals.
Applications
Potent and selective small molecules inhibitors of human GALK can be used as:
(1) Novel therapeutics to treat Classic Galactosemia; and
(2) Valuable research tools to probe the role played by galactose metabolism and protein/lipid glycosylation in normal and disease conditions.
Selective small molecules inhibitors of GHMP kinases can potentially be used as novel antimicrobials or therapeutics that modulate the cholesterol biosynthetic pathway.
Patent Status
International Patent Application No.
WO2009023773
claiming priority from U.S. Provisional Application 60/956,012 and U.S. Utility patent application 61/056,545, filed May 28, 2008
was published on February 19, 2009.
Licensing Opportunity
Seeking collaborative research and licensing options.
About the Inventors
Kent Lai, Ph.D., MBA, Associate Professor of Pediatrics, is the Principal Investigator of the ongoing study. Dr. Lai's research projects, currently funded by National Institutes of Health, American Heart Association and other private foundations, focus on drug discovery and inborn errors of metabolism.
Klaas Wierenga, MSc, MD, FACMG, is an Assistant Professor of Pediatrics and a Board-Certified Clinical Geneticist. Dr. Wierenga is known for his research work on sickle cell anaemia and other human genetic diseases.
Mr. Manshu Tang, MS, is currently a Ph.D. student in Dr. Lai's laboratory. Before Mr. Tang joined the Ph.D. program at UM, he worked in the biotechnology industry in China.
Together, the three inventors have published more than 50 peer-reviewed articles on various scientific and medical subjects.
Selected References
Wierenga KJ, Lai K, Buchwald P, & Tang M, 2008. "High throughput screening for human galactokinase inhibitors" J Biomol Screen 13: 415-423.
Lai K, Langley SD, Khwaja FW, Schmitt EW & Elsas LJ, 2003. "Galactose-1-phosphate uridyltransferase deficiency causes UDP-hexose deficit in human galactosemic cells" Glycobiology Journal 13: 285-294.
Elsas LJ, & Lai K, 1998. "Molecular biology of galactosemia" Genetics in Medicine 1: 40-48.
