This technology includes the use of a beclin 1 inhibitor, 17-hydroxy Wortmannin, for the treatment of TRAIL-resistant colon cancer. TRAIL (TNF-related apoptosis-inducing ligand) binds to death receptors (DR4/DR5) and activates apoptosis in cancer cells. Multiple clinical trials have focused on promoting TRAIL-induced death but have had a lack of efficacy due to TRAIL resistance developing quickly in cancer cells. Recent work has found that this resistance may be mediated by a lack of activation of the apoptosis/autophagy regulator beclin 1.

This technology includes the use of pyridines for anticancer treatment. A common feature of cancer cells is a high level of reactive oxygen species with a concomitant increase of two antioxidative systems to combat the toxicity: the glutathione and thioredoxin systems. Inhibiting either, or both, of these systems is a promising avenue to target cancer cells. Thioredoxin Reductase 1 (Trxr1) is an important selenoprotein in the thioredoxin antioxidative system which has been implicated as a potential anti-cancer target.

This technology includes the use of proteasome inhibitors, such as Bortezomib, for the treatment of the most prevalent form of Charcot-Marie-Tooth disease type 1A (CMT1A). Duplication of the peripheral myelin protein 22 (PMP22) gene, normally involved in myelination of the peripheral nervous system, is the causative agent in most forms of CMT1A. A drug discovery program was initiated and found that proteasome inhibitors can be used to target PMP22.

This technology includes the discovery and use of novel selective 12-LO (lipoxygenase) inhibitors, 4-((2-hydroxy-3-methoxybenzyl)amino)benzenesulfonamide derivatives, for attenuating large clots and for the treatment of Type 1/2 diabetes. A 12-LO inhibitor could be a potent intracellular approach to block platelets from forming large clots in response to vessel injury or activation of the coagulation pathway, either due to diabetes and/or cardiovascular disease. Blocking clot formation can significantly decrease the occurrence of myocardial infarction and death.

NCATS has developed a highly diverse synthetic library that will allow for the rapid identification of novel nanobodies that bind to a wide arrange of target antigens. The humanized framework used to construct the library will facilitate the transition of lead candidates into patient studies. Several highly potent SARS-CoV-2 nanobodies (antibodies) have been identified and are available for further development.

NCATS is actively seeking licensing for the 1) a synthetic library and 2) the potent neutralizing antibodies with activity against SARS-CoV-2.

The invention provides two vascularized, multi-chip models for the alveoli and the small airway. Both models comprise a perfusable three-dimensional (3D) microvascular network consisting of human primary microvascular endothelial cells, fibroblasts, and pericytes with a differentiated lung epithelial layer exposed at the air-liquid interface (ALI) on top, built on a high-throughput, 64-chip microfluidic plate platform. The platform does not require the support of a permeable membrane and the epithelial cells are directly seeded on the perfused microvascular network.

Recent studies have identified the G-protein-coupled receptor (GPCR) for insulin-like 3 peptide (INSL3), relaxin family peptide receptor 2 (RXFP2), as an attractive target for the treatment of bone diseases such as osteoporosis and rare bone diseases such as osteogenesis imperfecta. Currently, the most effective available treatment for osteoporosis is an expensive hormone therapy that requires daily injections. A stable, orally deliverable drug is a much more desirable alternative. Our RXFP2 agonists perform as well as the natural ligand INSL3 in cellular assays.

3D spheroids have emerged as powerful drug discovery tools given their high-throughput screening (HTS) compatibility. The present invention presents a method for generating functional neural spheroids with differentiated human induced pluripotent stem cell (hiPSC)-derived neurons and astrocytes at cell type compositions mimicking specific regions of the human brain.

This technology includes five microRNA mimics which were identified to improve the functional expression of hard-to-express membrane protein. These miRNAs are: hsa-miR-22-5p; hsa-miR-18a-5p, hsa-miR-22-3p, hsa-miR-429 and hsa-miR-2110. Improving expression level of recombinant mammalian proteins is vital, as the adequate supply of correctly folded proteins is the prerequisite for all structure and function studies.

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. The novel molecules have potential to treat Th17-related autoimmune diseases.