摘要:
The present invention provides methods and compositions for treating various diseases through selective killing of targeted cells using a combinatorial targeting approach. The invention features protoxin fusion proteins containing a cell targeting moiety and, a modifiable activation moiety which is activated by an activation moiety not naturally operably found in, on, or in the vicinity of a target cell. These methods also include the combinatorial use of two or more therapeutic agents, at minimum comprising a protoxin and a protoxin activator, to target and destroy a specific cell population.
摘要:
Provided are crystalline forms of a compound having an inhibitory effect on sodium-dependent glucose cotransporter SGLT2. The invention also provides pharmaceutical compositions, methods of preparing the crystalline compound, and methods of using the crystalline compound, independently or in combination with other therapeutic agents, for treating diseases and conditions which are affected by SGLT or SGLT2 inhibition.
摘要:
Provided are methods of treating obesity and effecting desired weight loss or preventing undesired weight gain by administration of a preferential muscarinic acetylcholine receptor M1 antagonist, optionally with at least one antidepressant other than a selective muscarinic acetylcholine receptor M1 antagonist. The preferential muscarinic acetylcholine receptor M1 antagonist, optionally can be administered with an anti-obesity agent, for example, an anorexiant. The invention also provides for pharmaceutical compositions and kits for administration of at least one selective muscarinic acetylcholine receptor M1 antagonist in combination with at least one antidepressant other than a selective muscarinic acetylcholine receptor M1 antagonist.
摘要:
Provided are crystalline forms of a compound having an inhibitory effect on sodium-dependent glucose cotransporter SGLT2. The invention also provides pharmaceutical compositions, methods of preparing the crystalline compound, and methods of using the crystalline compound, independently or in combination with other therapeutic agents, for treating diseases and conditions which are affected by SGLT or SGLT2 inhibition.
摘要:
Provided are compounds having an inhibitory effect on sodium-dependent glucose cotransporter SGLT. The invention also provides pharmaceutical compositions, methods of preparing the compounds, synthetic intermediates, and methods of using the compounds, independently or in combination with other therapeutic agents, for treating diseases and conditions which are affected by SGLT inhibition.
摘要:
Methods for modulating immune cell signaling are provided. In general such methods involve modulating an interaction between a PDZ protein and a PDZ ligand protein whose interaction affects the composition and/or distribution of lipid rafts in an immune cell. Modulators that enhance or inhibit such interactions are also disclosed, as well as methods of screening for such modulators.
摘要:
Disclosed are methods and compositions for reducing coronary artery stenosis, restoring blood flow to infarcted myocardium, improving myocardial perfusion, reducing heart attacks or other adverse cardiovascular events, or treating symptoms of inadequate myocardial function in a mammal involving administering to the mammal (a) a compound that includes eicosapentaeneoic acid or docosahexaeneoic acid and (b) a cholesterol-lowering therapeutic, combined with dietary restrictions (resulting in aggressive loading of marine lipids), whereby a serum LDL concentration of less than 75 mg/dl (and preferably less than 55 mg/dl) is achieved. One particular method involves administering to the mammal a combination that includes (a) a compound that includes an eicosapentaeneoic or docosahexaeneoic acid (for example, a marine lipid) and (b) a cholesterol synthesis or transfer inhibitor, and which may also optionally include aspirin and/or niacin. The methods and compositions of the invention may also further include a bile acid sequestrant and/or buspirone. Also disclosed are methods for treating heart disease that involve administration of buspirone.
摘要:
The present invention features novel methods for generating cell lines and mammals with site-specific genetic modifications of interest. The methods involve homologous recombination between an artificial chromosome having a modification of interest and an endogenous chromosome of a cell. The resulting modified cells can be used in standard methods to generate genetically modified mammals. These mammals can be used in a variety of screening methods to identify compounds useful for the treatment or prevention of disease. Additionally, cells that have been modified to eliminate a mutation associated with a disease can be transplanted into patients for the treatment of a disease.
摘要:
Disclosed is a method of directing a cellular response in a mammal by expressing in a cell of the mammal a chimeric receptor which causes the cells to specifically recognize and destroy an infective agent, a cell infected with an infective agent, a tumor or cancerous cell, or an autoimmune-generated cell. The chimeric receptor includes an extracellular portion which is capable of specifically recognizing and binding the target cell or target infective agent, and (b) an intracellular portion of a protein-tyrosine kinase which is capable of signalling the therapeutic cell to destroy a receptor-bound target cell or a receptor-bound target infective agent. Also disclosed are cells which express the chimeric receptors and DNA encoding the chimeric receptors.
摘要:
The invention relates to a fusion protein which comprises an immunoglobulin of the IgM, IgG1 or IgG3 immunoglobulin class, wherein the variable region of the light or heavy chain has been replaced with CD4 or fragment thereof which is capable of binding to gp120. The invention also relates to an immunoglobulin-like molecule comprising the fusion protein of the invention together with an immunoglobulin light or heavy chain. The invention also relates to a method of treating HIV or SIV infection comprising administering the fusion proteins or immunoglobulin-like molecules of the invention to an animal. The invention also relates to assays for HIV or SIV comprising contacting a sample suspected of containing HIV or SIV gp120 with the immunoglobulin-like molecule of fusion protein of the invention, and detecting whether a complex is formed.