This technology includes a novel APEl small molecule inhibitor, which exhibits potent in vitro activity and potentiates the cytotoxicity of DNA damaging agents. APEl is the primary mammalian enzyme responsible for the removal of abasic (AP sites) in DNA and functions as part of the base excision DNA repair pathway (BER). BER is instrumental in the repair of DNA damage caused by DNA alkylating agents (e.g., many cancer chemotherapeutics). Thus, inhibition of this pathway should potentiate the cytotoxicity of such compounds.

This technology includes LDHA inhibitors that have been synthesized and tested for the treatment of glycolytic cancers. These compounds may have improved activity over previous compounds.

This technology includes a new class of compounds, called remodelins, which can be used to prevent airway remodeling and prevent lung fibrosis. Currently no effective therapies are available for lung fibrosis. This compound could also be employed as a treatment for asthma.

This technology includes a series of small molecule organic compounds, called remodelins, that are synthetic derivative analogs of a parent compound discovered by screening of a Chembridge library. The novel synthetic derivative analogs were generated through multiple iterations of compounds directed by in vitro experiments. The invention also includes use of these or related molecules to treat cancer and/or glaucoma.

This technology includes novel systemic adeno-associated virus (AAV)-mediated CRISPR gene therapy technology. While some diseases (e.g., retinal diseases) can be treated through local gene transfer, many diseases such as Duchenne Muscular Dystrophy (DMD) require systemic therapy. The CRISPR technology has two components, the Cas9 endonuclease, and the gRNA. To explore systemic CRISPR therapy, we co-delivered the AAV.Cas9 and AAV.gRNA vector to mdx mice, a mouse DMD model. Direct delivery to muscle yielded efficient gene correction.

Scientists at NCATS have developed an analog of Methotrexate (MTX) that incorporates the proteasome-targeting properties of E3-ubiquitin ligase small molecule ligands (MTX-PROTACs) to directly bind to the MTX target dihydrofolate reductase (DHFR) and mark the protein for proteasomal degradation. This unique property may dramatically lower the therapeutic dose required in a treatment setting.

Aldehyde dehydrogenase enzymes (ALDHs) have a broad spectrum of biological activities through the oxidation of both endogenous and exogenous aldehydes. Unbalanced expression levels of ALDHs have been associated with a variety of disease states such as alcoholic liver disease, Parkinson’s disease, obesity, and multiple types of cancers. ALDH1A1 also plays a major role in preserving the tumor microenvironment via differentiation, self-protection, and proliferation of cancer stem cells.

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 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 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.