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: The disclosure provides methods of treating cancer in a subject or preventing a relapse or reducing the incidence of relapse of cancer in a subject in remission, comprising administering to the subject: (a) a therapeutically effective amount of an immunotherapeutic agent, e.g., an immune checkpoint blockade therapy, an adoptive cellular therapy, a marrow-infiltrating lymphocytes, an adenosine A2aR inhibitor, or an antibody; and (b) a compound 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).

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: 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.

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: Methods and compounds are disclosed for treating inflammatory bowel disease (IBD) by using Prostate Specific Membrane Antigen (PSMA) inhibitors.

Abstract: The disclosure provides methods of treating cancer in a subject or preventing a relapse or reducing the incidence of relapse of cancer in a subject in remission, comprising administering to the subject: (a) a therapeutically effective amount of an immunotherapeutic agent, e.g., an immune checkpoint blockade therapy, an adoptive cellular therapy, a marrow-infiltrating lymphocytes, an adenosine A2aR inhibitor, or an antibody; and (b) a compound 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).

Abstract: Methods for buccally, sublingually, or intranasally administering a prodrug of propofol to a subject in need of treatment thereof in an amount sufficient to deliver a therapeutically effective amount of propofol to the subject are disclosed.

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: Prodrugs of glutamine analogs, such as prodrugs of acivicin, 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, are provided.

Abstract: The use of a class of prodrugs of 2-PMPA that alter tissue distribution of 2-PMPA to non-prostate tissues is disclosed. The presently disclosed prodrugs preferentially distribute to healthy tissues including the kidney, lacrimal glands, and salivary glands, which represent sites of off-target binding and toxicity for PSMA-targeted prostate cancer imaging agents and therapies. Accordingly, the 2-PMPA prodrugs can be used to pretreat, bind to, and shield the kidney and salivary glands from PSMA-targeted cytotoxic or radiotherapy.

Abstract: The disclosure provides methods of treating a condition, disease, or disorder in a subject that involves metabolically reprogrammed cells whose activation, function, growth, proliferation, or survival depends on increased activity of at least one metabolic pathway selected from the group consisting of glutamine metabolism, glycolysis, and fatty acid synthesis, comprising administering to the subject a compound 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).

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

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. 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 methods of treating cancer in a subject or preventing a relapse or reducing the incidence of relapse of cancer in a subject in remission, comprising administering to the subject: (a) a therapeutically effective amount of an immunotherapeutic agent, e.g., an immune checkpoint blockade therapy, an adoptive cellular therapy, a marrow-infiltrating lymphocytes, an adenosine A2aR inhibitor, or an antibody; and (b) a compound having formula (1): 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).

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.