Novel Small Molecule Agonists of the Relaxin Receptor as Potential Therapy for Heart Failure and Fibrosis

The present invention is directed to novel small molecule agonists of the mammalian relaxin family receptor 1 (RXFP1), including human RXFP1. Activation of RXFP1 induces: 1) vasodilation due to up-regulation of the endothelin system; 2) extracellular matrix remodeling; 3) moderation of inflammation by reducing levels of inflammatory cytokines; and 4) angiogenesis. Small molecule agonists of RXFP1 may be useful in treating acute heart failure (AHF), scleroderma, fibrosis, other conditions associated with the biology of relaxin, and in improving reproductive health and wound healing.

Discovery of potent and selective D3 antagonist with alleviated hERG liability and optimized pharmacokinetic properties

One of the most challenging hurdles in creating safe and effective new medicines for many diseases is finding drugs that are effective without causing off-target cardiac issues, such as cardiac arrythmias. In collaboration with NIDA, scientists at NCATS have developed a series of novel and highly specific dopamine D3 receptor agonists and antagonists that have potential to target and treat Parkinson’s disease, Schizophrenia, Depression, and substance-use disorders including opioid addiction.

Non-invasive diagnostic and prognostic assay for early stage lung cancer

In the United States alone, one of four cancer deaths occur from lung cancer and there are over 8 million individuals considered to be at high-risk due to cigarette smoking and other behaviors. It's well known that early detection of cancer significantly improves survival of this disease, however a lack of lung cancer screenings and analysis precludes fast results at a low cost.

Anti-Viral Compounds that Inhibit HIV Activity

Several novel tropolone derivatives have been identified that inhibit HIV-1 RNase H function and have potential for anti-viral activity due to reduced cellular toxicity.  Inhibiting RNase H function is a potential treatment for many viral infections, since RNase H function is essential for viral replication for many pathogenic retroviruses such as HIV-1 and HIV-2.  Although many hydroxytropolone compounds are potent RNase H inhibitors biding at the enzymatic active site, they are limited as therapeutic candidates by their toxicity in mammalian cells.  The toxicity thought to

Small Molecule Activators of Human Pyruvate Kinase for Treatment of Cancer and Enzyme-Deficient Hemolytic Anemia

NIH investigators have discovered a series of small compounds with the potential to treat a variety of cancers as well as hemolytic anemia. Contrary to most cancer medications, these molecules can be non-toxic to normal cells because they target a protein specific to the metabolic pathways in tumors, thus representing a significant clinical advantage over less-specific chemotherapeutics.

Caspase Inhibitors Useful for the Study of Autoimmune or Inflammatory Diseases

Novel and potent caspase 1 inhibitors are available for licensing. In particular, this technology discloses potent and selective caspase 1 inhibitors that target the active site of the enzyme. Caspase 1 is known to play a pro-inflammatory role in numerous autoimmune and inflammatory diseases and therefore represents an excellent target for treatment of a broad range of diseases, including but not limited to Huntington's, amyotrophic lateral sclerosis, ischemia, rheumatoid arthritis, osteoarthritis, inflammatory bowel disease, and sepsis.

Pyruvate Kinase M2 Activators for the Treatment of Cancer

NIH investigators have discovered a series of small compounds with the potential to treat a variety of cancers as well as hemolytic anemia. Contrary to most cancer medications, these molecules can be non-toxic to normal cells because they target a protein specific to the metabolic pathways in tumors, thus representing a significant clinical advantage over less-specific chemotherapeutics.

Novel Tocopherol and Tocopheryl Quinone Derivatives as Therapeutics for Lysosomal Storage Disorders

Novel tocopherol derivatives and tocopheryl quinone derivatives useful in the decrease of lysosomal substrate accumulation, the restoration of normal lysosomal size, and the treatment of lysosomal storage disorders (LSDs) are provided. The inventors have discovered that tocopherol and tocopheryl quinone derivatives with side chain modifications (such as terminal tri-halogenated methyl groups) exhibit improved pharmacokinetics, modulation of mitochondrial potential and restoration of some LSDs phenotypes.

Use of Antihistamine Compounds for the Treatment of Hepatitis C Virus

The vast majority of people infected with Hepatitis C Virus (HCV) will have chronic infection. Over decades, this can lead to liver disease and liver cancer. In fact, HCV infection is the leading cause of liver transplants in the U.S. Several new drugs have recently come into the market that will likely change the HCV treatment paradigm. However, the effectiveness of these new drugs can vary depending on the HCV genotype. Thus, there is still the need for additional new therapeutics against HCV.
Subscribe to NCATS