Dr. Edmond Ma Dik-Lung, Associate Professor of our Department, received a total of HK$1,200,000 from the Government’s Health and Medical Research Fund 2016-17 for his research project entitled “Design and development of BRD4 inhibitors for the treatment of BRD4-related cancers”. The project led by Dr. Ma was conducted in collaboration with Prof. Wong Man-Shing, Professor, Hong Kong Baptist University and Dr. Leung Chung-Hang, Associate Professor, Institute of Chinese Medical Sciences of the University of Macau and his team.
BRD4 has been shown to play an important role in sustaining the proliferation of metastatic melanoma. The dysregulation of BRD4 has been implicated in a wide array of human disorders including cancer, obesity, kidney disease, lung fibrosis and other inflammatory diseases, which render it a legitimate and novel target for epigenetic therapy. To date, over five BRD4 inhibitors have been subjected to clinical trials, but none of these have yet been approved for human use due to their adverse side effects. Although BRD4 inhibition has shown promise as an anti-cancer strategy, there remains significant room for the discovery of novel scaffolds as BRD4 inhibitors to develop more potent anti-cancer drug leads that have superior potency and reduced side effects.
In such a case, the research team plans to employ high-throughput molecular docking to identify potential BRD4 inhibitors from natural product/natural product-like databases. The utilization of virtual screening allows rapid identification of ligands with high efficacy and selectivity, thereby greatly reducing the number of compounds that need to be evaluated in vitro. The team will also evaluate the ability of the lead candidates to inhibit the interaction between chromatin and BRD4, c-myc transcription and cellular migration and invasion in cello. The most potent compounds identified after preliminary biological evaluation will be subjected to computer-aided structural-based modification and lead optimization in order to develop potent drug candidates for the treatment of metastatic melanoma cancer in an in vivo mouse xenograft model. The team envisages that the development of BRD4 inhibitors from natural product scaffolds or their in-house database could potentially generate useful anti-proliferative agents to complement existing therapies for the treatment of cancer, particularly metastatic melanoma cancer.
The funding will be spent on the purchase of molecular docking software, natural product compound libraries, chemical and biochemical reagents, and for the recruitment of talented staffs. Dr. Ma said, “We are pleased to receive the funding support from the Health and Medical Research Fund this year. We anticipate that in depth studies of this research projects would be developed expansively, in which the results would be of high interest to the scientific community.”