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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 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.

This technology includes mutant isocitrate dehydrogenase (IDH1) inhibitors to be utilized as anticancer therapy. These potent inhibitors are aimed at lowering levels of the oncometabolite–2-hydroxyglutarate.

This technology includes selective inhibitors of the human enzyme galactokinase (EC 2.7.1.6), which may be useful for the treatment of Galactosemia and other diseases caused by aberrant galactose metabolism, including cancer. These compounds inhibit the first step in galactose metabolism, thereby eliminating the build-up of toxic metabolites during the aberrant metabolism of galactose, as well as inhibitor the entry of galactose into glycolysis and other downstream assays.

This technology includes the identification and use of heterocyclic alcohol compounds, including RITA and N-BIC, for the treatment of SULT1A1-expression cancers. A high-throughput screen (qHTS) was performed using >1,000 caner cell lines identified a compound called YC-1 (also called Lificiguat) that is effective across cancer cell types that express the phase 2 detoxifying enzyme SULT1A1.

This technology includes inhibitors of the Eya phosphatase which can be utilized as anticancer therapy. The Eya proteins are essential co-activators of the Six1 transcription factor, a gene that is abnormally re-expressed in a large percentage of breast cancers. This over-expression plays a causal role in the initiation and metastatic development of breast cancers. The Eya family of proteins was also found to contain a unique haloacid dehalogenase phosphatase domain with protein Tyr phosphatase activity which can potentially play a role in Six1- mediated breast tumorigenesis.

This technology includes a series of imidazo[1,2-a]pyridines that potently inhibit FLT3, which can be utilized as an anticancer agent. These molecules retain potent binding and activity against FLT3 tyrosine kinase domain and gatekeeper mutations. This chemotype exhibits superior anti-leukemic activity against clinically-relevant FLT3-mutant acute myeloid leukemia (AML) in vitro and in vivo. Tyrosine kinase domain mutations are a common cause of acquired resistance to FLT3 inhibitors used to treat FLT3-mutant AML.

This technology includes a series of imidazo[1,2-a]pyridines that potently inhibit FLT3, which can be utilized as an anticancer agent. These molecules retain potent binding and activity against FLT3 tyrosine kinase domain and gatekeeper mutations. This chemotype exhibits superior anti-leukemic activity against clinically-relevant FLT3-mutant acute myeloid leukemia (AML) in vitro and in vivo. Tyrosine kinase domain mutations are a common cause of acquired resistance to FLT3 inhibitors used to treat FLT3-mutant AML.

This technology includes a method of analyzing the potency of membrane transporter protein-based drugs acting on intracellular antioxidant and redox response pathways (and associated apoptosis pathways), wherein the drug delivery and activity is lipid associated. The present invention is a cell-based bioassay for measuring the bioactivity of drug substance and formulated drug product by determining the drug's dose-dependent inhibitory effects on 4 hydroxynonenal (4-HNE)-induced antioxidant response element (ARE) activity.