Abstract: Ferroptosis (cell death mediated by iron-dependent lipid peroxide accumulation) results from lipid peroxidation of phospholipids containing polyunsaturated fatty acyl moieties. Glutathione, the key cellular antioxidant capable of inhibiting lipid peroxidation via the activity of the enzyme glutathione peroxidase 4 (GPX-4), is generated directly from the sulfur-containing aminoacid cysteine, and indirectly from methionine via the transsulfuration pathway. Cysteine and methionine deprivation (CMD) in the diet can synergistically increase RSL3-mediated cell death and lipid peroxidation in both murine and human glioma cell lines and in ex-vivo organotypic slice cultures. A cysteine-depleted, methionine-restricted diet can improve survival in an syngeneic orthotopic murine glioma model. This CMD diet leads to profound in-vivo metabolomic, proteomic and lipidomic alterations, leading to improvements in the efficacy of ferroptotic therapies in glioma treatment with a non-invasive dietary modification.

Abstract: Various embodiments relate to compounds, having structures according to Structure A or Structure B, as specified herein. The compounds according to various embodiments may inhibit NT5C2 nucleotidase. The compounds according to various embodiments may synergistically decrease cell viability of NT5C2 R367Q mutant lymphoblasts when used in combination with 6-mercaptopurine (6-MP) to treat a cancer. The cancer may be, but is not limited to, acute lymphoblastic leukemia. Various embodiments relate to a compositions that may include one or more compounds according to any embodiment described herein or a pharmaceutically acceptable salt or derivative thereof and a pharmaceutically acceptable carrier. Various embodiments relate to methods of treating cancer. The method may comprise administering a therapeutically effective amount of one or more compounds according to any embodiment described herein or a pharmaceutically acceptable salt or derivative thereof.

Abstract: The present invention relates to erastin analogs, particularly compounds of formulae VI, VIa, VII, and VIIa, as well as compounds 19, 20, and 20. The invention also relates to pharmaceutical compositions containing such analogs and to methods of treating a condition in a mammal with such analogs and compositions.

Abstract: The present invention relates to compounds effective in preventing neuronal cell death, which may be used in the treatment of neurodegenerative diseases. It is based, at least in part, on the discovery that particular compounds were effective in preventing neuronal death in model systems of Huntington's Disease.

Abstract: The invention features a method for treating a patient having a cancer or other neoplasm by administering to the patient two compounds simultaneously or within 14 days of each other in amounts sufficient to treat the patient.

Abstract: The invention features a method for treating a patient having a cancer or other neoplasm by administering to the patient two compounds simultaneously or within 14 days of each other in amounts sufficient to treat the patient.

Abstract: The present invention relates to compounds effective in preventing neuronal cell death, which may be used in the treatment of neurodegenerative diseases. It is based, at least in part, on the discovery that particular compounds were effective in preventing neuronal death in model systems of Huntington's Disease.

Abstract: The present invention relates to compounds effective in preventing neuronal cell death, which may be used in the treatment of neurodegenerative diseases. It is based, at least in part, on the discovery that particular compounds were effective in preventing neuronal death in model systems of Huntington's Disease.

Abstract: The invention relates to methods of screening for binding partners, especially binding partners essential for the biological activity of erastin (e.g. VDACs such as VDAC3). The invention also provides reagents and methods for effective killing of cancer cells with erastin and related compounds or derivatives.

Abstract: The invention features a method of screening two-entity or higher order combinations for biological activity using combinational arrays. The method includes the steps of: (a) providing the entities, (b) creating an array of combinations of entities, (c) providing a test element that includes one or more distinct biological moieties, (d) contacting the array of combinations of entities with the test element under conditions that ensure that each entity/test element contacting is segregated from the others, (e) detecting or measuring a property of the test element, and (f) identifying combinations of entities that cause an effect on the property of the test element that is different from the effect of an entity of the combination by itself.

Abstract: The invention features a method for treating a patient having a cancer or other neoplasm by administering to the patient two compounds simultaneously or within 14 days of each other in amounts sufficient to treat the patient.

Abstract: The present invention relate to methods of identifying a genotype-selective agent. In certain embodiments, the invention relates to agents that selectively suppress huntingtin-induced toxicity to engineered neuronal cells.

Abstract: Embodiments of the invention are directed toward methods and devices for constructing assay arrays including a combination of constituent compositions from constituent arrays. The combined compositions are evaluated, in some embodiments of the invention, to identify combinations with a combination effect. Other embodiments of the invention are directed toward constructing constituent arrays in various configurations to facilitate the production of assay arrays. Such embodiments include: constructing constituent arrays and assay arrays with corresponding composition and assay control sets; constructing constituent arrays with a unique set of origin locations and corresponding sets of derivative locations; varying the concentrations utilized for a constituent composition; and composing assay arrays corresponding to a virtual sparse assay array. Other embodiments of the invention are directed towards systems and method of evaluating the activity of combined compositions in an assay array.

Abstract: Embodiments of the invention are directed toward methods and devices for constructing assay arrays including a combination of constituent compositions from constituent arrays. The combined compositions are evaluated, in some embodiments of the invention, to identify combinations with a combination effect. Other embodiments of the invention are directed toward constructing constituent arrays in various configurations to facilitate the production of assay arrays. Such embodiments include: constructing constituent arrays and assay arrays with corresponding composition and assay control sets; constructing constituent arrays with a unique set of origin locations and corresponding sets of derivative locations; varying the concentrations utilized for a constituent composition; and composing assay arrays corresponding to a virtual sparse assay array. Other embodiments of the invention are directed towards systems and method of evaluating the activity of combined compositions in an assay array.

Abstract: This invention relates to therapies for diseases involving splicing defects, such as spinal muscular atrophy (SMA), and methods to identify compounds for treating this disease. The invention specifically provides for therapies comprised of small molecule compounds identified by cell-based high-throughput screening assays. These assays utilize engineered splicing constructs that fuse pre-mRNA fragments to a reporter gene. The fragments contain exons and at least one intron of a gene mutated in such a way to cause disease. Additionally, the invention provides for methods to monitor the effects of drugs on splicing and gene expression in vivo, in transgenic animals.

Abstract: The invention involves high throughput methods for identifying properties of cells under a variety of cellular conditions. The high throughput methods have a variety of uses, including methods for identifying cellular modulators such as pharmacological agents or environmental conditions, methods for identifying a cellular phenotype and methods for identifying novel genes.