TARGETED AREAS OF DRUG DISCOVERY
Neurological/Neuropsychiatric Disorders
Anxiety & Depression
The World Health Organization predicts that by 2020, depression will be the second-largest cause of the global health burden. It represents the central nervous system disorder with the highest prevalence. Development of new classes of drugs for neuropsychiatric disorders is an area of intense research for Triton. The fact that there are nearly 500 molecules published from coral reef invertebrates that are closely related to the endogenous ligands for serotonin, dopamine and histamine receptors underscores the significant utility and strength of marine-based drug discovery and development in this area. Triton has successfully identified a number of early leads from three distinct structural classes, of which seven critical leads have been targeted for late preclinical and early clinical investigation. These drug leads are unmodified natural products with good metabolic stability and pharmacokinetics and show significant antidepressant activity without indications of acute toxicity.
Sleep Disorders
According to the NIH, about 40 million Americans each year suffer from long-term chronic sleep disorders and an additional 20 million Americans experience occasional sleep problems. Sleep disorders are responsible for $16 billion per year in medical costs alone. This figure does not include the costs of decreased concentration, disturbances in work efficiency and the negative social aspects caused by sleep deprivation. Most of the available insomnia medications may cause drowsiness the next day and very often they do not provide a restful, healthy sleep. As well, addiction can occur with several classes of sleep inducing drugs. With an objective to discover new, more effective and safe sleep medications, Triton has identified a potent sedative and sleep inducing marine natural product drug lead. The potency of this lead compound is accompanied with good metabolic stability and absence of acute toxicity.
Infectious Diseases
Methicillin-resistant Staphylococcus aureus (MRSA)
Staphylococcus aureus, commonly known as “staph” is a common bacteria that can live on the skin. Staph infections in the body are usually minor and are treated with antibiotics. Over the decades, some strains have become resistant, thus causing more serious infections resulting in pneumonia or even death. MRSA, which was first discovered in 1961, is a variation of staph that is resistant to antibiotic treatment with methicillin, amoxicillin, penicillin, oxacillin and cephalosporins. Rapid development of multi drug-resistant microbial pathogens is a serious problem and MRSA is constantly adapting. Triton is aware of the great need for novel antimicrobial agents from available natural products, and researchers have identified naturally occurring compounds found to be highly selective against MRSA.
Malaria
Malaria is a tropical infection caused by parasites of the species Plasmodium that are transmitted to humans by the Anopheles mosquito. Inside the body, these parasites multiply in the liver and then infect red blood cells. The Center for Disease Control estimates that 350-500 million cases of malaria occur worldwide each year and over one million people die, most of them young children in Africa. In past decades, chloroquine and other aminoquinolines have been utilized as frontline antimalarial agents. However, increasing drug resistance has made it essential to develop new chemotherapeutic agents in addition to combination therapies with different modes of action. Triton is dedicated to the development of novel and effective antimalarial drugs. Research efforts in this area have lead to the discovery of highly potent antimalarial alkaloids produced by a marine bacterium.
Fungus
Mycoses are ubiquitous like bacterial infections; however, transmission from person to person is less likely. Infections occur most frequently in the immune-compromised, but can become life threatening in healthy individuals if left untreated. Drug resistance is not currently wide-spread but the development of resistance to azole-type antibiotics poses a serious threat for the millions of AIDS patients worldwide. The recent emergence of cyclic peptidic antifungal drugs has opened the door for research with this class of molecules. With a limited number of antifungal drugs available in the market today, Triton researchers are intensely focused on the discovery and synthetic optimization of similar compounds with significant antifungal activity.
Cancer
According to the U.S. National Cancer Institute (NCI), although the overall death rates due to cancer continue to decline, the incidence rates of cancer of the liver, pancreas, kidney, esophagus, and thyroid are rising. With over 1.4 million new cases and deaths from cancer in the United States in 2007, cancer treatment spending continues to rise. The search for superior drugs for the treatment of cancer has focused for decades on naturally-occurring sources for anticancer therapy. Triton has a highly active ongoing drug discovery program for the control of cancer with drug leads in various stages of preclinical development. These leads are modified marine peptides, derived from second generation compounds and novel metabolites of marine origin, showing significant anti-tumor activity. In particular, early results indicate that the compounds are selective for Non-Small Cell Lung Cancer (NSCL), colon, ovarian, breast cancers, and prostate cancer cells.
Immune Suppression
Immunosuppressant drugs are used during organ transplantation to reduce the possibility of transplant rejection and serious complications, including death. As well, there are several diseases for which immunosuppressive drugs are the preferred therapy. With an estimated 10,000 new bone marrow transplant patients annually worldwide, the global market potential today is more than $50 million. Additionally, the market potential is significant in the other autoimmune or inflammatory diseases that may be amenable to treatment including rheumatoid arthritis and osteoarthritis. Triton’s immune suppression leads are based on a group of marine alkaloids that selectively inhibit key kinases involved in inflammation, fever and other immune responses. These leads have a mode of action that is distinctly different than clinically utilized drugs, as candidates for combination therapies, and are more potent than currently available drugs.