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This technology includes the use of auranofin for the treatment of Chronic Lymphocytic Leukemia (CLL). Auranofin is currently approved for the treatment of rheumatoid arthritis and has been shown to display anti-cancer activity. CLL is a blood and bone marrow disease that usually progresses over a lengthy period of time and normally occurs in middle-age adults. The current therapeutic options for CLL patients are limited, and there are few therapies under development.

This technology includes the use of a chemical series (compounds NCGC00117362, NCGC117328, NCGC00117505, NCGC00117477, NCGC00117166 and their analogs) as potential treatment for ovarian cancer. These compounds were identified through a high throughput screen (HTS) of 44,806 compounds implemented at NCATS using a layered 3D organotypic assay model of human ovarian cancer metastatic microenvironment containing primary human mesothelial cells, primary human fibroblasts, and extracellular matrix.

This technology includes a strategy to generate antibodies of rabbit origin, both polyclonal and monoclonal, which have strong affinity to the TAT sequence and which enable specific immunocapture or immunodetection of TAT containing frataxin and analogs for quantitative or qualitative assays. In addition, antibodies that react with the FXN region have also been generated with this strategy. The HIV virus encoded a translational activator protein containing a 12 amino acid domain which permits transmembrane delivery of any therapeutic protein containing the sequence.

This technology includes the utility of the novel small molecule inhibitors of ALDH1A1 (RALDH1) in combination with immunotherapy for the treatment of hepatocellular carcinoma (HCC). Recently it was shown that the ALDH1A1 catalyzed production of retinoic acid (RA) in tumor cells promotes their differentiation into immunosuppressive antigen-presenting cells. Therefore, blocking RA production by tumor cells and/or blocking RA signaling in monocytes using our ALDH1A1 inhibitors can alleviate immunosuppression and engender anti-tumor immune responses.

This technology includes a series of novel benzene-1,4-disulfonamides that activate TRPML1 receptor. The TRPML1 receptor is a lysosomal Ca2+ channel that has been shown to be involved in controlling lysosome functions, among then the maintenance of the integrity of the plasma membrane and the modulation of autophagosome-lysosome fusion. The improved ability of the receptor to deliver Ca2+ ions to the cytosol had been correlated with its capacity to modulate autophagy and lysosome exocytosis.

This technology includes an assay capable of monitoring glycosome formation for use in high throughput screening (HTS). The reversible assembly and disassembly of a multi-enzyme complex, known as the glycosome, visualized by GFP-labeled human phosphofructokinase-1 (PFK1), is employed as an intracellular marker in human cells to screen small molecule libraries under high-content imaging in a high-throughput fashion. The glycolytic enzymes have been proposed to form a multi-enzyme complex in the cell.

This technology includes a newly discovered molecule 2,6-Dimethoxy-4-(5-Phenyl-4-Thiophen-2-yl-1H-Imidazol-2-yl)-Phenol (DPTIP) as potent inhibitor of neutral sphingomyelinase 2 (nSMase2), to be used for the treatment of neurodegenerative and oncologic diseases. This discovery was identified through unbiased screening of the National Center for Advancing Chemical Sciences (NCATS) chemical library using our human neutral sphingomyelinase assay.

This technology includes a new chemical series of substituted bicyclic heteroaryl small molecules as potent bromodomain-containing protein BRD4 inhibitors used for the treatment of cancer and inflammatory diseases. The optimization led to compounds with good potency in enzymatic assay ( 100 nM) and in MV4-11 cell-based assay ( 1000 nM) as well as excellent early ADME properties. We also identified N-methyl 2 pyridone and N-methyl pyrrolopyridone are great replacements of di-methylisoxazole. This chemical series also exhibited good ADME profiles, including PK.

This technology includes the identification of small molecule inhibitors of nuclear factor erythroid-2 related factor-2 (Nrf2) as therapeutic anticancer agents. Multiple mechanisms lead to frequent dysregulation of Nrf2 activity in cancer cells, which promotes both tumorigenesis and therapeutic resistance. Dysregulated Nrf2-Keap1 pathway is a novel determinant of chemoresistance/radioresistance and inhibition of Nrf2 signaling will enhance the efficacy of chemotherapeutic and radiotherapy.

This technology includes a novel chemotype against mutant (R 132H) isocitrate dehydrogenase 1 (IDH1) enzyme to be utilized as an anticancer therapy. We have progressed the structure activity relationship (SAR) and optimized the compound to be low nanomolar inhibitor of the enzyme with low nanomolar inhibition of the target in cells. These compounds lower 2-hydroxyglutarate, which has been termed an 'oncometabolite' and is common in a subset of cancers including glioma, cholangiocarcinoma, chondrosarcoma and acute myeloid leukemia.