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The technology includes Pink1 knockout HeLa cells that were generated using CRISPR technology. Pink1 is the key master gene to trigger degradation of mitochondria, mitophagy, and is implicated in familial Parkinson Disease. Knocking out Pink1 allows us to study the roles of Pink1 in many aspects of mitophagy and to display Pink1-dependent or independent activity. To create the HeLa cells, two CRISPR gRNAs targeting exon 1 and exon 7 of the Pink1 genome were used for transfection with Cas9 and GFP-C1 reporter. Cells were sorted 2 days after transfection and plated out in 96-well plates.

This invention includes HeLa cells that are engineered to inducibly express a mutant form of ornithine decarboxylase that is targeted to the mitochondrial matrix and forms insoluble protein aggregates. The presence of unfolded proteins in the matrix causes the accumulation of the mitochondrial kinase PINK1 and the E3 ubiquitin ligase PARK2/Parkin. These proteins play a critical role in degrading the mitochondria where they are expressed, a process call mitophagy. Mutations in these two genes are associated with familial Parkinson disease.

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 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 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]pyrazines 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 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 two new salt forms for (2R,6R)-hydroxynorketamine (2R,6R-HNK), which is the lead molecule being developed for treatment-resistant depression. Currently, 2R,6R-HNK is being developed as the HCl salt. The HCl salt is slightly hygroscopic at high RH. This is a potential liability, especially in an oral pill form. Recently the malonate and salicylate salt have been discovered and found to have excellent crystalline behavior while also not having the hygroscopic liability the HCl salt holds. This represents a clear advantage.

This technology includes a series of diphenylpropanamides as potent and selective RORgt inhibitors for the treatment of Th17-related autoimmune diseases. The retinoic acid-related orphan receptor RORgt plays an important role in the differentiation of thymocytes, lymphoid tissue inducer cells, and inflammatory T helper-expressing interleukin 17a (Th17) cells. Small molecule RORgt inhibitors may provide means to regulate Th17 mediated immune response.

This technology includes a series of diphenylpropanamides as potent and selective RORgt inhibitors for the treatment of Th17-related autoimmune diseases. The retinoic acid-related orphan receptor RORgt plays an important role in the differentiation of thymocytes, lymphoid tissue inducer cells, and inflammatory T helper-expressing interleukin 17a (Th17) cells. Small molecule RORgt inhibitors may provide means to regulate Th17 mediated immune response.