This technology includes a method for creating functional, brain region-specific neural spheroids that can be used for disease modeling and therapeutic testing of compounds for neurological diseases. The developed protocol uses somatic cells, including iPSC-derived neurons, as well as astrocytes using means such as 96- or 384-well ultra-low attachment round-bottom plates. Spheroids have been generated using this method that model brain regions such as the ventral tegmental area and prefrontal cortex, which are implicated in Parkinson’s and Alzheimer’s disease.

This technology includes the identification and use of small molecules to rescue cells undergoing ferroptosis, a type of programmed cell death. These small molecules can be used as treatments in situations where epithelial cells are being damaged, including respiratory disorders, brain injury (including traumatic brain injury), renal injury, radiation-induced injury, and neurodegenerative disorders. Ferroptosis is a type of programmed cell death that is triggered by an increased presence of oxidants.

This technology includes the combination therapy of tyrosine kinase inhibitors (TKIs) and tigecycline as a potential new treatment for acute myeloid leukemia (AML). The existing treatments available for AML are not adequate; for patients older than 60, the prognosis is poor, with a two-year survival probability of less than 10%. Tigecycline is a glycylcycline antibiotic that induces cell death via inhibition of mitochondrial protein synthesis.

This technology includes the use of a new class of molecules (nanomolar ALK2 inhibitor) to impede bone morphogenetic proteins (BMP) signaling for the treatment of Fibrodysplasia ossificans progressiva (FOP). FOP is a rare disease, characterized by malformation of the great (big) toes during embryonic development. Individuals with FOP have an identical heterozygous activating mutation (R206H) in the gene encoding ACRV1 (also known as ALK2), a BMP type 1 receptor.

This technology includes the use of a new class of molecules (nanomolar ALK2 inhibitor) to impede bone morphogenetic proteins (BMP) signaling for the treatment of Fibrodysplasia ossificans progressiva (FOP). FOP is a rare disease, characterized by malformation of the great (big) toes during embryonic development. Individuals with FOP have identical heterozygous activating mutation (R206H) in the gene encoding ACRV1 (also known as ALK2), a BMP type 1 receptor.

The present invention is directed to a synthesis of a dual-target inhibitor of cannabinoid-1 (CB1R) receptor and inducible nitric oxide synthase, and more specifically, to an improved process for synthesis of (S,1E,NE)-N-(1-aminoethylidene)-3-(4-chlorophenyl)-4-phenyl-N'-((4-(trifluoromethyl)phenyl)sulfonyl)-4,5-dihydro-1H-pyrazole-1-carboximidamide.

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 methods for screening compounds and compositions useful for inhibiting or reducing platelet deposition, adhesion, and/or aggregation. The present invention further relates to methods of treatment or prophylaxis of thrombotic disorders, including stroke, myocardial infarction, unstable angina, abrupt closure following angioplasty or stent placement, thrombosis induced by peripheral vascular surgery, peripheral vascular disease or thrombotic disorders resulting from atrial fibrillation or inflammation.

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 the use of the Anneal-Pool-Ligate-Sequence method (APLS) to quantify the cellular expression of dozens of genes for high throughput chemical library screening. This method is performed by culturing eucaryotic cells in 384-well format microplates, treating the cells with a library of chemicals, and producing cell lysates. Oligodeoxynucleotide (oligo) pairs representing (21) selected genes, and carrying index sequences for each well (384) and microplate (26), are annealed to mRNAs in cell lysates.