2017-03-07

HKBU research project receives HK$1.2 million boost from Health and Medical Research Fund in support of the development of BRD4 inhibitors for the treatment of BRD4-related cancers
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.”