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Immunoglobulins play a key role in the immune system. CDC has developed and tested hybridoma cell lines (monoclonal antibody (mAb) clones) for human IgG and other immunoglobulins. The mAbs generated from those hybridomas could be used as a reagent (second Ab) of anti-human immunoglobins in a diagnostic assay for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the virus that causes COVID-19 (coronavirus disease 2019) and other assays that detect antigen specific antibodies from human sera.

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.

The current invention provides nucleic acid sequences comprising the genomes of infectious hepatitis C viruses (HCV) of genotype 1a and 1b. It covers the use of these sequences, and polypeptides encoded by all or part of the sequences, in the development of vaccines and diagnostic assays for HCV and the development of screening assays for the identification of antiviral agents for HCV.

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.

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 the combination therapy of tyrosine kinase inhibitors (TKIs) and tigecycline as a potential new treatment for acute myeloid leukemia (AML). The existing treatments available for AML are not adequate; for patients older than 60, the prognosis is poor, with a two-year survival probability of less than 10%. Tigecycline is a glycylcycline antibiotic that induces cell death via inhibition of mitochondrial protein synthesis.

The present invention is directed to a synthesis of a dual-target inhibitor of cannabinoid-1 (CB1R) receptor and inducible nitric oxide synthase, and more specifically, to an improved process for synthesis of (S,1E,NE)-N-(1-aminoethylidene)-3-(4-chlorophenyl)-4-phenyl-N'-((4-(trifluoromethyl)phenyl)sulfonyl)-4,5-dihydro-1H-pyrazole-1-carboximidamide.