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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 have changed the HCV treatment paradigm. However, the effectiveness of these new drugs can vary depending on the HCV genotype. Furthermore, all oral, interferon free therapeutic regimens for HCV infection will need combinations of drugs that target different aspects of the HCV life cycle.

The coronavirus disease 2019 (COVID-19) is caused by a novel RNA enveloped coronavirus, SARS-CoV-2 when the virus enters human airway cells via an ACE2-mediated entry process. This entry pathway is facilitated by the cell surface heparan sulfate proteoglycan (HSPG), which enhances viral attachment to the cell surface. Researchers at NIDDK and NCATS have discovered a collection of FDA-approved drugs that can interfere with the entry of SARS-CoV-2. These drugs can be grouped into three classes based on the distinct steps in the viral entry pathway that they target.

This technology includes the development and use of small molecule activators of pyruvate kinase (PK) for the treatment of inherited nonspherocytic hemolytic anemia, including PK deficiency. PK deficiency is caused by an inherited deficiency in an enzyme that reduces the lifespan of red blood cells. More than 150 unique mutations have been identified in the PK gene that lead to decreased activity in this essential enzyme in the glycolytic pathway. The prematurely lysed red blood cells can lead to jaundice, splenomegaly, and a hemolytic anemia.

This technology includes the synthesis and use of novel PI3K and HDAC dual inhibitors for the treatment of several cancers. Phosphatidylinositol 3-kinase (PI3K) is activated in many human cancers, and inhibition of these kinases is an established cancer treatment. Histone deacetylases (HDACs) are key regulators of the cell cycle that function through regulating expression of tumor suppressors (p21 and p27), c-Myc and cyclin D1. HDAC inhibition is an emerging therapeutic approach for the treatment of several cancers.

This technology includes the use of the small molecule metarrestin (ML246) for the treatment of several types of pancreatic cancer. A subcellular structure called the perinucleolar compartment (PNC) is frequently found in metastatic tumors and cancer stem cells. Reduction of PNC prevalence followed by medicinal chemistry was used to identify metarrestin as a compound that reduces PNC prevalence without significantly impacting cell viability. In vitro and in vivo animal work have demonstrated desirable pharmacokinetic properties as well as a reduction in metastatic burden and extended survival.

This technology includes a method for creating functional, brain region-specific neural spheroids that can be used for disease modeling and therapeutic testing of compounds for neurological diseases. The developed protocol uses somatic cells, including iPSC-derived neurons, as well as astrocytes using means such as 96- or 384-well ultra-low attachment round-bottom plates. Spheroids have been generated using this method that model brain regions such as the ventral tegmental area and prefrontal cortex, which are implicated in Parkinson’s and Alzheimer’s disease.

This technology includes the use of autophagy upregulators such as ML246/metarrestin to counteract the tolerance that can build up through the therapeutic use of cannabinoids. Long-term administration of cannabinoids rapidly introduces tolerance and physical dependence, limiting its medical use and may lead to addiction and withdrawal symptoms. Cannabinoids mediate their effect by binding to and activating the cannabinoid receptor 1 (CNR1/CB1). Chronic exposure leads to CNR1 being targeted for degradation through a process of autophagy.

There is an acute deficit in chemical synthesis with respect to benchtop tools that are specifically designed to address the capability and efficiency of certain key aspects of chemical synthesis, namely reaction preparation, product isolation, and solvent removal. Chemical research currently relies upon a variety of devices that function in a manner that is disconnected, as well as difficult to integrate and automate; collectively, these device challenges hinder the efficient isolation and purification of desired chemical synthesis products.

This technology includes the identification and use of small molecules to rescue cells undergoing ferroptosis, a type of programmed cell death. These small molecules can be used as treatments in situations where epithelial cells are being damaged, including respiratory disorders, brain injury (including traumatic brain injury), renal injury, radiation-induced injury, and neurodegenerative disorders. Ferroptosis is a type of programmed cell death that is triggered by an increased presence of oxidants.

This technology includes a device to allow chemists to process crude reaction mixtures with the objective of isolating the desired product from reaction by-products and other solvents and impurities to provide material of adequate quality and purity to be submitted for further chromatographic purification or used directly in subsequent reactions. The instrument serves in facilitating the integration of a close-to-universal set of isolation techniques collectively referred to as “solid-phase extraction” (SPE) methods.