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METHOD FOR DETECTING AND IMAGING APOPTOSIS

Technology Benefits
Monitoring of apoptosis
Technology Application
The compounds and methods are useful in the diagnosis and treatment of conditions characterized by apoptosis, including cancer, cardiac disease, neurologic disease including stroke, and autoimmunity. For example, the detecting and monitoring can be used to assess the effect of chemotherapy and radiation therapy in the treatment of cancer. The compounds and methods of this invention offer distinct advantages over corresponding compounds and methods based on Annexin V.
Detailed Technology Description
The invention relates to the detection and monitoring of cells undergoing apoptosis or necrosis and to the selective delivery of therapeutic or diagnostic (labeling) agents to these cells. The invention is based on our discovery that dehydrogenase enzymes, such as LDH, ADH, ALDH, MDH, are, in addition to being leaked from dying cells, taken up and retained by these cells. The compounds and methods are based on conjugates formed with dehydrogenase enzymes and can also be used for screening of compounds that can modulate apoptosis.The method includes the steps of contacting a test cell with a conjugate of dehydrogenase (linked to a label) and an agent, under conditions that otherwise induce apoptosis in the test cell. The invention also provides the pharmaceutical composition, of the compounds, suitable for administration to a patient.
Supplementary Information
Inventor: Luesch, Hendrik | Kanchan, Taori | Paul, Valerie J.
Priority Number: US8129418B2
IPC Current: A61K0031429 | A61P002528 | A61P003500 | C07D051316
US Class: 514366 | 540456
Assignee Applicant: University of Florida Research Foundation Inc.inesville | Smithsonian Instituteshington
Title: Macrocyclic compounds and methods of treatment
Usefulness: Macrocyclic compounds and methods of treatment
Summary: For modulating (preferably inhibiting) the activity of cell proliferation in a subject. The cell is a cancer or tumor cell. For treating a subject (i.e. mammal, preferably primate or human) suffering from or susceptible to a cell proliferation related disorder or disease selected from cancer, solid tumor, colon cancer, breast cancer, bone, brain and others (e.g. osteosarcoma, neuroblastoma, colon adenocarcinoma). The disorder is an angiogenesis disorder, or solid tumor. For treating diseases and disorders associated with stem cell fate and that are affected by cell differentiation, dedifferentiation or transdifferentiation; histone deacetylase (HDAC) mediated disease or disorder; and cutaneous T-cell lymphoma, and memory loss inducing neurogenesis. For enhancing memory retention, enhancing memory formation, increasing synaptic potential or transmission, or increasing long term potentiation (LTP) in a subject (claimed). Also for treating conditions in a subject including but not limited to myogenesis, neurogenesis, osteogenesis and osteoblast maturation; and keloids, psoriasis, inflammatory disorders, neurodegenerative diseases, protozoal and latent viral infections, (fibro)proliferative disorders, multiple sclerosis, autoimmune, demyelinating and degenerative disease of the human central nervous system (CNS), and stroke.
Novelty: New macrocyclic compounds useful for treating e.g. cancer, tumor, angiogenesis disorder, cutaneous T-cell lymphoma, memory loss inducing neurogenesis and osteoblast maturation
Industry
Disease Diagnostic/Treatment
Sub Category
Cancer/Tumor
*Abstract
The invention relates to the detection and monitoring of cells undergoing apoptosis or necrosis and to the selective delivery of therapeutic or diagnostic (labeling) agents to these cells using newly discovered biomarkers.
Country/Region
USA

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