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This technology includes processes for the synthesis of VBP15 (17a,21-dihydroxy-16a-methyl-pregna-1,4,9(11)-triene-3,20-dione) of high purity and large quantities as a treatment for Duchenne muscular dystrophy. The synthesis of VBP15 has several deficiencies which has hindered larger-scale preparation for clinical evaluation and potential manufacturing. The deficiencies included formation of significant levels of undesired epoxide impurity, formation of undesired ketone impurity, and resultant need for costly chromatographic purification.

This technology includes a novel pyrazole-based compound NCGC00274266 (MLS000714501) that inhibits LDH-A with an IC50 of approximately 20 µM with low efficacy that can be used as an anti-cancer therapeutic. Structure-activity relationship studies on this compound led to hydroxypryazole-based compounds and discovery that the hydroxypyrazole compound and related analogs demonstrated a strong metal-dependent activity.

This technology includes a group of 20 drugs that can be further developed as a treatment for chordoma. Chordoma is a rare, slow-growing malignant tumor arising from remnants of the fetal notochord, with a high recurrence rate and no effective chemotherapy agents. These 20 drugs inhibited chordoma cell growth, with potencies ranging from 10 to 370 nM in the chordoma cell line UCH1 cells. These agents also had significant inhibitory effects on chordoma patient cells, C24, C25, and C32.

This technology includes the compositions and methods for inhibiting PIN1 for the treatment of disorders characterized by elevated PIN1 levels (e.g., immune disorders, proliferative disorders, and neurodegenerative disorders) with small molecules. Pin1 dysregulation has been associated with a number of pathological conditions. In particular, PIN1 has been shown to promote oncogenesis by modulating several oncogenic signaling pathways and its overexpression has been shown to correlate with poor clinical outcome.

Monoclonal antibodies (mAbs) have become a mainstay of therapy for many cancers. However, antibody therapy is not completely effective in some applications due to loss of the target surface antigen on cancer cells. Such mAb-induced “escape variants” are no longer sensitive to the therapeutic mAb therapy. It was observed that the escape variants carried covalently bound complement activation fragments, especially C3d. NIH inventors have generated several C3d-specific mouse and rabbit monoclonal antibodies to re-target cells that have escaped from mAb therapy.

This technology includes a system that allows for robust differentiation of human-induced pluripotent stem cells (iPSC) into motor neurons within a time frame of 7 to 10 days. To differentiate the iPSC, a stable transgene is inserted into the CLYBL safe harbor locus in the human genome using TALENs. The transgene allows for doxycycline-inducible expression of the transcription factors (NGN2, ISL1, and LHX3) that are needed for the cells to differentiate to motor neurons. The technology is described in detail in the protocol paper published by Fernandopulle et al, cited below.

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.