Abstract: Methods for treating age-related sarcopenia and/or enhancing longevity by administering one or more GCPII inhibitors, wherein the one or more GCPII inhibitors are selected from a phosphonate-based GCPII inhibitor, a phosphinate-based GCPII inhibitor, a phosphoramidate-based GCPII inhibitor, a thiol-based inhibitor, a hydroxamate-based inhibitor, and a urea-glutamate based GCPII inhibitor, including one or more of 2-PMPA and prodrugs thereof, L-DOPA, D-DOPA, caffeic acid, and prodrugs thereof, a hydroxamate-based prodrug, and a dendrimer 2-PMPA conjugate are disclosed.

Abstract: Small molecule inhibitors of neutral sphingomyelinase 2 (nSMase2) and their use for treating neurodegenerative diseases, such as, neurodegenerative diseases associated with high levels of ceramide, including, but not limited to Alzheimer's disease (AD), HIV-associated neurocognitive disorder (HAND), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS), and, in other aspects, for treating cancer or HIV-1, are provided.

Abstract: Glutamine antagonists and their use for treating oncological, immunological, and neurological diseases are disclosed. Also disclosed are methods for treating an oncological, immunological, infectious or neurological disease or disorder, the method comprising administering to a subject in need of treatment thereof a therapeutically effective amount of a glutamine antagonist of the disclosure or the pharmaceutical composition thereof. Also disclosed are methods of enhancing the effects of an immune checkpoint inhibitor, enabling a subject to respond to an immune checkpoint inhibitor, or enabling the toxicity or the dose or number of treatments with an immune checkpoint inhibitor to be reduced, comprising administering to a subject in need of treatment thereof a therapeutically effective amount of a glutamine antagonist of the disclosure or the pharmaceutical composition thereof, and an immune checkpoint inhibitor.

Abstract: Caffeic Acid, L-DOPA, and D-DOPA and prodrugs thereof for treating a disease, condition, or disorder associated with excess glutamate carboxypeptidase II (GCP-II) are disclosed.

Abstract: Provided are glutamine antagonists and prodrugs of glutamine analogs having formula (I): and pharmaceutically acceptable salts thereof, wherein R1, R2, R2?, and X are as defined as set forth in the specification, for use in preventing and/or treating acute kidney injury.

Abstract: Compositions of dendrimers conjugated with one or more glutamine antagonist(s) that inhibit glutamine metabolism, preferably in activated microglia, and methods of use thereof for treating, alleviating, and/or preventing one or more neurological, oncological, and/or immune disorders associated with pathogenic or dysregulated glutamine-dependent pathways and/or glutamate transmission, have been developed. Dendrimers conjugated with one or more glutamine antagonists effectively inhibit the activity of glutaminase without any systemic toxicity. Dendrimers conjugated with one or more glutamine antagonists accumulate in activated microglia associated with the injured or diseased cells and tissues.

Abstract: Prodrugs of itaconic acid and 1- and 4-methyl itaconic acid and their use for treating a disease, disorder, or condition associated with inflammation are disclosed.

Abstract: Methods for the use of prodrugs of itaconic acid and 1- and 4-methyl itaconic acid for inducing hair growth and treating an inflammatory, or immune activation (adaptive or innate), skin condition or other condition associated with hair loss are disclosed.

Abstract: Prodrugs of small molecule inhibitors of neutral sphingomyelinase 2 (nSMase2) and their use for treating neurodegenerative diseases, such as, neurodegenerative diseases associated with high levels of ceramide, including, but not limited to Alzheimer's disease (AD), HIV-associated neurocognitive disorder (HAND), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS), and, in other aspects, for treating cancer, are provided.

Abstract: The present disclosure provides prodrugs of 6-diazo-5-oxo-L-norleucine (DON) for use in treating or preventing a disease, disorder, or condition in which the inhibition of glutamine-utilizing enzymes provides a benefit.

Abstract: Methods for treating a Human Immunodeficiency Virus (HIV) infection comprising administering to a subject in need of treatment thereof an effective amount of a small molecule nSMase2 inhibitor.

Abstract: Methods and compounds are disclosed for treating a disease or condition by inhibiting PSMA (Prostate Specific Membrane Antigen) using prodrugs of 2-PMPA.

Abstract: The disclosure provides compounds having formula (I): and the pharmaceutically acceptable salts thereof, wherein R1, R2, R2?, and X are as defined as set forth in the specification. Compounds having formula (I) are prodrugs that release glutamine analogs, e.g., 6-diazo-5-oxo-L-norleucine (DON). The disclosure also provides compounds having formula (I) for use in treating cancer.

Abstract: The disclosure provides compounds having formula (I): and the pharmaceutically acceptable salts thereof, wherein R1, R2, R2?, and X are as defined as set forth in the specification, for use in treating cognitive deficits and/or psychiatric disorders, such as those associated with neurological or neurodegenerative disorders, psychiatric or mood disorders, and HIV-associated neurocognitive disorders (HAND). Compounds having formula (I) are prodrugs that release glutamine analogs, e.g., 6-diazo-5-oxo-L-norleucine (DON).

Abstract: Prodrugs of 6-mercaptopurine (6-MP) and methods of their use for treating cancers and autoimmune diseases are disclosed.

Abstract: Prodrugs of hydroxamate-based GCPII inhibitors and methods of their use for treating a disease or condition are disclosed.

Abstract: Positive allosteric modulators (PAMs) of Mas-related G protein-coupled receptor X1 (MRGPRX1) and their use for treating neuropathic pain is disclosed.

Abstract: Novel N4-substituted decitabine analogs are disclosed that exhibit promising in vitro and in vivo therapeutic activity. These novel compounds were shown to be resistant to deamination via cytidine deaminase (CDA) metabolism and provide a unique pharmacokinetic profile versus decitabine, while retaining the ability to induce DNA demethylation in target cells. These novel compounds can be used for treating hematological cancers, as well for new therapeutic interventions, including bacterial or viral pneumonia, acute respiratory distress syndrome, pulmonary fibrosis, transplantation and checkpoint inhibitor-induced adverse events, including pneumonitis.

Abstract: Dendrimer compositions and methods for the treatment of cancer or autoimmune diseases are described. The compositions include dendrimers complexed or conjugated with one or more active agents for the treatment or alleviation of one or more symptoms of cancer or autoimmune diseases. The dendrimers may include one or more ethylene diamine-core poly(amidoamine) (PAMAM) hydroxyl-terminated generation-4, 5, 6, 7, 8, 9, or 10 dendrimers. The active agents may be immunomodulatory agents such as STING agonists, CSF1R inhibitors, PARP inhibitors, VEGFR tyrosine kinase inhibitors, MEK inhibitors, glutaminase inhibitors, TIE II antagonists, and CXCR2 inhibitors, and STING antagonists. Methods of using the dendrimer compositions to treat cancer, bone disease or inflammatory diseases are also provided.

Abstract: Methods for treating one or more diseases associated with neutral sphingomyelinase 2 (nSMase2) in a subject in need of treatment thereof, the method comprising administering to the subject a therapeutically effective amount of 2,6-dimethoxy-4-(5-phenyl-4-thiophen-2-yl-1H-imidazol-2-yl)-phenol (DPTIP) or a pharmaceutically acceptable salt thereof, are disclosed.