Abstract: The ?2-adrenergic receptor (?2AR) is a primary target in the treatment of airway diseases such as asthma and chronic obstructive pulmonary disease (COPD). Since ?-agonist treatment of airway disease can have severe side effects, compounds that attenuate the side effects of ?-agonists have been identified via their ability to inhibit ?2AR interaction with ?-arrestins. These compounds are specific for the ?2AR and effectively protect against the desensitization observed with ?-agonist treatment in model cells and airway tissue. The present disclosure provides compounds and methods for treating airway disease, such as but not limited to COPD and/or asthma.

Abstract: Compounds, compositions and methods for suppressing an immune response to polyethylene glycol (PEG) are provided.

Abstract: The present invention provides compounds useful for treating, ameliorating or preventing a disease or disorder that is caused, induced or characterized by abnormal reduction in glutamate transporter activity or abnormal increase in extracellular CNS glutamate concentration in a subject. In certain embodiments, the compound stimulates a glutamate transporter.

Abstract: The present disclosure provides in one aspect compounds of Formula I. In certain embodiments, the compounds of the disclosure are useful for treating, ameliorating or preventing a disease or disorder that is caused, induced or characterized by abnormal reduction in glutamate transporter activity or abnormal increase in extracellular CNS glutamate concentration in a subject. In certain embodiments, the compounds of the disclosure stimulate a glutamate transporter.

Abstract: The present invention provides compounds useful for treating, ameliorating or preventing a disease or disorder that is caused, induced or characterized by abnormal reduction in glutamate transporter activity or abnormal increase in extracellular CNS glutamate concentration in a subject. In certain embodiments, the compound stimulates a glutamate transporter.

Abstract: The disclosure provides compounds of formula (II) having the structure: Compounds of formula (II) are fractalkine receptor agonists and useful in treating, preventing or minimizing metastasis in a subject diagnosed with cancer. The compounds of the disclosure are further useful in treating central nervous system diseases (such as, but not limited to, HIV Associated Neurocognitive Disorders (HAND), and/or Alzheimer's disease), pain, inflammation (such as, but not limited to, arthritis), cardiovascular disease (such as, but not limited to, undesired vascular smooth muscle proliferation, atherosclerosis, coronary vascular endothelial dysfunction, and/or coronary artery disease), and/or multiple sclerosis.

Abstract: The disclosure provides compounds of formula (I) having the structure: Compounds of formula (I) are fractalkine receptor agonists and useful in treating, preventing or minimizing metastasis in a subject diagnosed with cancer. The compounds of the invention are further useful in treating central nervous system diseases (such as, but not limited to, HIV Associated Neurocognitive Disorders (HAND), and/or Alzheimer's disease), pain, inflammation (such as, but not limited to, arthritis), cardiovascular disease (such as, but not limited to, undesired vascular smooth muscle proliferation, atherosclerosis, coronary vascular endothelial dysfunction, and/or coronary artery disease), and/or multiple sclerosis.

Abstract: Methods for treating cancer are disclosed which comprise administering to a subject T cells which have been pretreated ex vivo or in vitro with fenofibric acid (FFA), an FFA prodrug, or a derivative thereof that has PPAR-? agonist activity. These compounds promote the use of fatty acid catabolism rather than glucose for energy and promote enhanced recovery of, and biomass production by, the pre-treated T cells. Still other methods comprise co-administering to a subject having a cancer characterized by a solid tumor an immunotherapeutic composition targeting an antigen or ligand on the tumor cell and the pretreated T cells. The method may also employ co-administration of a checkpoint inhibitor. Novel compositions comprise the pre-treated T cells. Novel FFA prodrugs are provided.

Abstract: The present invention provides compounds useful for treating, ameliorating or preventing a disease or disorder that is caused, induced or characterized by abnormal reduction in glutamate transporter activity or abnormal increase in extracellular CNS glutamate concentration in a subject. In certain embodiments, the compound stimulates a glutamate transporter.

Abstract: The invention provides compounds that are fractalkine receptor agonists and useful in treating, preventing or minimizing metastasis in a subject diagnosed with cancer. The compounds of the invention are further useful in treating central nervous system diseases (such as, but not limited to, HIV Associated Neurocognitive Disorders (HAND), and/or Alzheimer's disease), pain, inflammation (such as, but not limited to, arthritis), cardiovascular disease (such as, but not limited to, undesired vascular smooth muscle proliferation, atherosclerosis, coronary vascular endothelial dysfunction, and/or coronary artery disease), and/or multiple sclerosis.

Abstract: The present invention includes compositions that are useful in preventing or treating metastasis in a subject diagnosed with cancer. The present invention also includes methods of preventing or treating metastasis in a subject diagnosed with cancer, wherein the method comprises administering to the subject in need thereof an effective amount of a pharmaceutical formulation comprising at least one pharmaceutically acceptable carrier and at least one CX3CR1 or fractalkine antagonist.

Abstract: The present invention provides compounds useful for treating or preventing a brain-related disease or disorder. The present invention further provides a method of treating or preventing a brain-related disease or disorder in a patient, comprising administering to the patient a pharmaceutical composition comprising at least one compound of the invention. The present invention further provides a method of modulating the activity of a monoamine transporter.

Abstract: In an effort to discover therapies for treating diseases caused by EBV, a novel screening assay for identifying compounds that reactivate EBV latent infection and a family of small molecules based on a tetrahydrocarboline backbone were discovered. Specifically, the compounds have the structure of the formula (I), wherein R1-R11 are defined herein and activate/reactivate EBV in a variety of cell types in a patient and are, therefore, useful in preventing or treating EBV-positive cancer, optionally with an anti-viral agent. In screening these compounds, novel compositions, EBV-positive cell lines, and methods are provided.

Abstract: The present invention includes compounds useful in preventing, treating or ameliorating Sigma-related disorders or diseases. The compounds of the invention may modulate cellular protein homeostasis, which includes: translation initiation, folding, processing, transport, and degradation (including ubiquitin selective autophagy) of proteins. The present invention also includes methods of preventing, treating or ameliorating a Sigma-related disorder or disease in a subject in need thereof, the method comprising administering to the subject an effective amount of a Sigma-modulating compound. The present invention also includes methods of preventing, treating or ameliorating a Sigma-related disorder or disease in a subject in need thereof, the method comprising administering to the subject an effective amount of a Sigma-modulating compound, further comprising administering an effective amount of a compound that inhibits the ubiquitin proteasome system (UPS) and/or autophagic survival pathways.

Abstract: In an effort to discover therapies for treating diseases caused by EBV, a novel screening assay for identifying compounds that reactivate EBV latent infection and a family of small molecules based on a tetrahydrocarboline backbone were discovered. Specifically, the compounds have the structure of the formula (I), wherein R1-R11 are defined herein and activate/reactivate EBV in a variety of cell types in a patient and are, therefore, useful in preventing or treating EBV-positive cancer, optionally with an anti-viral agent. In screening these compounds, novel compositions, EBV-positive cell lines, and methods are provided.

Abstract: The present invention provides compounds useful for treating or preventing a brain-related disease or disorder. The present invention further provides a method of treating or preventing a brain-related disease or disorder in a patient, comprising administering to the patient a pharmaceutical composition comprising at least one compound of the invention. The present invention further provides a method of modulating the activity of a monoamine transporter.

Abstract: The present invention includes compounds useful in preventing, treating or ameliorating Sigma-related disorders or diseases. The compounds of the invention may modulate cellular protein homeostasis, which includes: translation initiation, folding, processing, transport, and degradation (including ubiquitin selective autophagy) of proteins. The present invention also includes methods of preventing, treating or ameliorating a Sigma-related disorder or disease in a subject in need thereof, the method comprising administering to the subject an effective amount of a Sigma-modulating compound. The present invention also includes methods of preventing, treating or ameliorating a Sigma-related disorder or disease in a subject in need thereof, the method comprising administering to the subject an effective amount of a Sigma-modulating compound, further comprising administering an effective amount of a compound that inhibits the ubiquitin proteasome system (UPS) and/or autophagic survival pathways.

Abstract: The present invention includes compositions that are useful in preventing or treating metastasis in a subject diagnosed with cancer. The present invention also includes methods of preventing or treating metastasis in a subject diagnosed with cancer, wherein the method comprises administering to the subject in need thereof an effective amount of a pharmaceutical formulation comprising at least one pharmaceutically acceptable carrier and at least one CX3CR1 or fractalkine antagonist.

Abstract: The present invention includes compounds useful in preventing, treating or ameliorating Sigma-related disorders or diseases. The compounds of the invention may modulate cellular protein homeostasis, which includes: translation initiation, folding, processing, transport, and degradation (including ubiquitin selective autophagy) of proteins. The present invention also includes methods of preventing, treating or ameliorating a Sigma-related disorder or disease in a subject in need thereof, the method comprising administering to the subject an effective amount of a Sigma-modulating compound. The present invention also includes methods of preventing, treating or ameliorating a Sigma-related disorder or disease in a subject in need thereof, the method comprising administering to the subject an effective amount of a Sigma-modulating compound, further comprising administering an effective amount of a compound that inhibits the ubiquitin proteasome system (UPS) and/or autophagic survival pathways.

Abstract: The present invention includes compositions that are useful in preventing or treating metastasis in a subject diagnosed with cancer. The present invention also includes methods of preventing or treating metastasis in a subject diagnosed with cancer, wherein the method comprises administering to the subject in need thereof an effective amount of a pharmaceutical formulation comprising at least one pharmaceutically acceptable carrier and at least one CX3CR1 or fractalkine antagonist.