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.

This technology includes a series of imidazo[1,2-b]pyridazines that display potent inhibition of FLT3, as well as potent binding and activity against FLT3 tyrosine kinase domain and gatekeeper mutations. This chemotype exhibits superior anti-leukemic activity against the common 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 relates to the discovery and development of a practical, scalable, and commercially viable method for the synthesis of the novel antifungal VT-1129. Cryptococcal meningitis (CM) is a fungal infection that is particularly prevalent in immune-compromised patients and can be treated by VT-1129. CM has a current estimated patient population of 1-1.25 million, predominately in sub-Saharan Africa and the developing world.

This technology relates to the creation and use of newly identified ligands to the D1 dopamine receptor (D1R). The D1 dopamine receptor is linked to a variety of neuropsychiatric disorders and represents an attractive drug target for the enhancement of cognition in schizophrenia, Alzheimer disease, and other disorders. These ligands are positive allosteric modulators (PAMs) that bind to the dopamine receptor at a site other than where dopamine binds and causes the receptor to have an increased response.

This technology relates to the description and therapeutic use of a small molecule that selectively binds to and activates the D3 dopamine receptor. Dopamine receptors (DARs) are members of the G protein-coupled receptor (GPCR) superfamily that play a critical role in cell signaling processes, especially modulating the transfer of information within the nervous system. Members of the DAR subfamilies share high sequence homology, especially the D2 and D3 DARs. Most currently available dopaminergic drugs cross-react with both subtypes to varying degrees.

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 development and use of small molecules that inhibit O-linked beta-N-acetylglucosamine (O-GlcNAc) transferase (OGT) for a variety of pathologies, including Alzheimer's disease, cancer, cancer, diabetes, and neurodegenerative disorders the treatment of cancer and as a potential antiviral. OGT is a ubiquitous enzyme that catalyzes the transfer of N-acetylglucosamine (GlcNAc) to the serine or threonine residues of nuclear and cytoplasmic proteins.

This technology includes three new compound classes displaying either differential or comprehensive antimalarial activity across geographically diverse lines. These compounds were identified from a quantitative high throughput screen of a novel chemical library with unique chemical complexity and are potential candidates for treating malaria.

This technology includes a series of imidazo[1,2-a]pyridines with potent inhibition of FLT3, which retains potent binding and activity against FLT3 tyrosine kinase domain and gatekeeper mutations. This chemotype exhibits superior anti-leukemic activity against the common 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 invention builds upon an earlier IP position with new analogs.

This technology includes a series of imidazo[1,2-a]pyridines with potent inhibition of FLT3, which retains potent binding and activity against FLT3 tyrosine kinase domain and gatekeeper mutations. This chemotype exhibits superior anti-leukemic activity against the common 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 invention builds upon an earlier IP position with new analogs.