摘要:
The present invention provides complex compounds reminiscent of natural products and libraries thereof, as well as methods for their production. The inventive compounds and libraries of compounds are reminiscent of natural products in that they contain one or more stereocenters, and a high density and diversity of functionality. In general, the inventive libraries are synthesized from diversifiable scaffold structures, which are synthesized from readily available or easily synthesizable template structures. In certain embodiments, the inventive compounds and libraries are generated from diversifiable scaffolds synthesized from a shikimic acid based epoxyol template. In other embodiments, the inventive compounds and libraries are generated from diversifiable scaffolds synthesized from the pyridine-based template isonicotinamide. The present invention also provides a novel ortho-nitrobenzyl photolinker and a method for its synthesis. Furthermore, the present invention provides methods and kits for determining one or more biological activities of members of the inventive libraries. Additionally, the present invention provides pharmaceutical compositions containing one or more library members.
摘要:
The invention involves identification of a mechanism of β-amyloid peptide cytotoxicity, which enables treatment of conditions caused by β-amyloid peptide aggregates by administration of compounds which antagonize the mechanism of cytotoxicity. The invention includes the identification and isolation of compounds which can reduce the neurotoxic effects of such aggregates. Methods for treating conditions resulting from neurotoxic β-amyloid peptide aggregates, such as Alzheimer's disease and pharmaceutical preparations are provided. Also provided are methods for selecting additional compounds which can reduce the neurotoxic effects of β-amyloid aggregates.
摘要:
The invention features a method of screening for drug-drug interactions using combinational arrays. The method includes the steps of: (a) receiving a test drug from a client; (b) contacting the test drug and at least 200 library drugs from a drug library in an assay under conditions that ensure that each test drug/library drug contacting is segregated from the others; (c) recording the result of the contacting step (b); (d) identifying combinations of drugs that produce a result in the assay that is different from the results produced by either drug of the combination by itself, wherein each identified combination indicates an interaction between the test drug and the library drug of the combination; and (e) communicating the results of the identifying step (d) to the client.
摘要:
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.
摘要:
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.
摘要:
The present invention relate to methods of identifying a genotype-selective agent. In certain embodiments, the invention relates to agents that are selectively toxic to engineered human tumorigenic cells.
摘要:
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.
摘要:
The present invention relate to methods of identifying a genotype-selective agent. In certain embodiments, the invention relates to agents that are selectively toxic to engineered human tumorigenic cells.
摘要:
The present invention provides complex compounds reminiscent of natural products and libraries thereof, as well as methods for their production. The inventive compounds and libraries of compounds are reminiscent of natural products in that they contain one or more stereocenters, and a high density and diversity of functionality. In general, the inventive libraries are synthesized from diversifiable scaffold structures, which are synthesized from readily available or easily synthesizable template structures. In certain embodiments, the inventive compounds and libraries are generated from diversifiable scaffolds synthesized from a shikimic acid based epoxyol template. In other embodiments, the inventive compounds and libraries are generated from diversifiable scaffolds synthesized from the pyridine-based template isonicotinamide. The present invention also provides a novel ortho-nitrobenzyl photolinker and a method for its synthesis. Furthermore, the present invention provides methods and kits for determining one or more biological activities of members of the inventive libraries. Additionally, the present invention provides pharmaceutical compositions containing one or more library members.
摘要:
The invention relates to methods for identifying agents, which induce oxidative cell death in a tumor cell. The invention further relates to methods for identifying tumor cells, which are sensitive to agents that induce oxidative cell death. The invention also relates to methods for identifying subjects who are suffering from tumors, which are sensitive to agents that induce oxidative cell death.