Why wine saves some people from heart disease.
Resverlogix describes MoA of RVX-208
2012-04-23 08:06 ET - News Release
Mr. Donald McCaffrey reports
RESVERLOGIX' RVX-208 IS THE FIRST BET BROMODOMAIN INHIBITOR IN CLINICAL TRIALS
Resverlogix Corp. is providing further information about the mechanism of action (MoA) by which RVX-208 increases apolipoprotein A-I (ApoA-I) production. The company's data show RVX-208 to be an inhibitor of the bromodomain and extraterminal domain (BET) proteins. RVX-208 acts on BET proteins, including BRD4, a member of the BET protein family, leading to increased transcription of the ApoA-I gene followed by production of more ApoA-I protein.
ApoA-I is the major protein component of high-density lipoprotein (HDL), a class of lipoproteins believed to reduce atherosclerosis through reverse cholesterol transport (RCT). The ability of RVX-208 to increase ApoA-I makes it the lead candidate in Resverlogix's pipeline for treating atherosclerotic cardiovascular disease. RVX-208 is an orally active small molecule, the first in a new class of compounds to enter into human clinical trials more than four years ago. Clinical benefits of RVX-208 are currently being explored in two concurrent phase 2b clinical trials (SUSTAIN and ASSURE), led by Cleveland Clinic.
"The finding that RVX-208 inhibits BET proteins is an important discovery for a wide scientific and medical audience," stated Dr. Norman Wong, chief scientific officer of Resverlogix. "This discovery is important because BET proteins are key players in epigenetics, a critical mechanism for regulating the expression of genes. Epigenetic processes are mediated by proteins, including the BET proteins, that act in concert with the DNA to make it transcriptionally active or dormant. This epigenetic control of gene expression plays a key role in the development and progression of many human diseases. The knowledge gained from studies of RVX-208 will guide Resverlogix in its search for additional compounds to treat some of these diseases," added Dr. Wong.
"The MoA of RVX-208 has allowed the company to expand the scope of its technology and the potential of its pipeline significantly," stated Donald McCaffrey, president and chief executive officer of Resverlogix. "We have been generating and filing new intellectual property since our discovery, and see the opportunity to initiate licensing and partnering discussions in the areas of atherosclerosis, oncology, autoimmune and Alzheimer's diseases where the MoA plays a pivotal role." Mr. McCaffrey added that "the value of this discovery was further validated when Dr. James Watson, in his first solo scientific publication since 1972, highlighted the promise of BRD4 as a therapeutic target and, in particular, against untreatable cancers."
As previously announced, Resverlogix will be hosting a conference call and webcast on April 23, 2012, commencing at 11 a.m. ET to present in further detail the MoA of RVX-208.
Conference call dial-in numbers:
Canada and United States toll-free dial-in number: 1-800-319-4610
Outside of Canada and the United States: 1-604-638-5340
Epigenetics
Epigenetics is the study of processes that enable information encoded in DNA to be expressed. Although DNA encodes the genes, by itself DNA cannot use these data. To use the data within DNA, it must work in concert with proteins. An essential aspect in this collaborative process is that both DNA and proteins are packaged together into chromosomes that reside within the cell's nucleus. There are thousands of different genes encoded within DNA, and to enable expression of these genes when called upon by the cell requires epigenetic processes. One of the key epigenetic processes involves the modification of chromosomal proteins by acetylation, methylation or phosphorylation, each of which is regulated by specific enzymes. These modified entities serve as bait for other proteins, including BET proteins, to bind to or "read" these modifications (the epigenetic code). As the BET proteins bind, they recruit additional proteins to regulate gene activity. When the gene becomes active, it leads to synthesis of messenger ribonucleic acid (mRNA), followed by translation of mRNA into a specific protein. In the past decade, tremendous progress has been made in understanding the role of epigenetics in human disease. This in-depth understanding has led to the development of medicines directed toward cancer, such as DNA methylation inhibitors and HDAC inhibitors. The discovery that RVX-208 is a BET bromodomain inhibitor adds new momentum to the promise of epigenetic mechanisms as a rich source of new medicines.
RVX-208
RVX-208 is a novel small molecule that stimulates endogenous ApoA-I production to trigger the synthesis of HDL. The use of this approach will enhance the functionality of HDL. ApoA-I is the major protein component of HDL. The main role of these particles is to act as the body's natural defence system against atherosclerosis by mediating a normal physiologic process called RCT. This pathway enables cholesterol, including that within atherosclerotic plaques of vessel walls, to be transported to the liver for further processing and elimination from the body. Enhanced RCT clearance of cholesterol from vessel walls is expected to reduce or prevent atherosclerosis. The ability of RVX-208 to increase ApoA-I production and thereby augment RCT differentiates it from other HDL therapies. RVX-208 is positioned to be one of the most promising drugs in development for the treatment of atherosclerosis. |
