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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 a novel Cellular Thermal Shift Assay (CETSA), named “Real-time CETSA” in which temperature-induced aggregation of proteins can be monitored in cells in real time across a range of compound concentrations and simultaneously across a temperature gradient in a high-throughput manner. Real-time CETSA streamlines the thermal shift assay and allows investigators to capture full aggregation profiles for every sample.

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.

The invention includes compounds and compositions for inhibiting phosphoglycerate mutase (PGM) activity. In some examples, the compounds selectively inhibit cofactor-independent PGM (iPGM). In particular embodiments, the compounds include one or more cyclic peptides.

Malaria continues to be a life-threatening disease, causing roughly 241 million cases and an estimated 627,000 deaths in 2020, mostly among African children, although in 2020 nearly half of the world’s population was at risk of malaria. There is a big financial burden for antimalarial treatment; direct costs (for example, illness, treatment, premature death) have been estimated to be at least US $12 billion per year and the cost in lost economic growth is many times more than that.

In the last decade, prescription opioid abuse and misuse has been a major contributor to mortality in the United States, resulting in a serious national public health crisis. Nearly 12 million Americans used prescription opioids nonmedically in 2018, with >67,000 people dying from an opioid overdose.

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.