The present disclosure relates to the use of PGC-1α expression to identify a subject that is conducive to treatment with a ma-485 inhibitor. In some aspects, the subject suffers from a disease or disorder associated with reduced PGC-1α expression. In some aspects, the PGC-1α expression is measured in the serum of the subject.

The disclosure provides, among other things, methods and uses for treating a disease or disorder, particularly tumors of a cancer patient, comprising conjointly administering effective amounts of a STING agonist, a cytokine, and an optional immune checkpoint inhibitor to the patient, wherein the STING agonist or the cytokine is intratumorally administered to the patient.

The disclosure provides, among other things, methods and uses for treating a disease or disorder, particularly tumors of a cancer patient, comprising conjointly administering effective amounts of a STING agonist, a cytokine, and an optional immune checkpoint inhibitor to the patient, wherein the STING agonist or the cytokine is intratumorally administered to the patient.

The invention relates to nicotinamide mononucleotide, a pharmaceutically acceptable precursor thereof, a pharmaceutically acceptable derivative thereof, or a pharmaceutically acceptable salt thereof, for the use thereof in the prevention and/or treatment of pain, in particular nociceptive pain; the invention relates as well to compositions that comprise the same.

The invention relates to nicotinamide mononucleotide, a pharmaceutically acceptable precursor thereof, a pharmaceutically acceptable derivative thereof, or a pharmaceutically acceptable salt thereof, for the use thereof in the prevention and/or treatment of pain, in particular nociceptive pain; the invention relates as well to compositions that comprise the same.

This disclosure provides compositions and methods for the targeted and localized in vivo delivery of oligonucleotides. Compositions containing targeted oligonucleotide-HES conjugates are provided as are methods of making and using the conjugates in therapeutic, diagnostic, and other applications. The oligonucleotide-HES complexes contained in the targeted oligonucleotide-HES conjugates can cross membranes in a receptor-independent manner and can deliver oligonucleotides to complementary sequences in the cytosol of live cells in vivo. The targeted oligonucleotide-HES conjugates have uses that include the targeted and/or localized delivery of antisense oligonucleotides, siRNAs, shRNAs, Dicer substrates, miRNAs, anti-miRNA, and other nucleic acid sequence in a living organism.

This disclosure provides compositions and methods for the targeted and localized in vivo delivery of oligonucleotides. Compositions containing targeted oligonucleotide-HES conjugates are provided as are methods of making and using the conjugates in therapeutic, diagnostic, and other applications. The oligonucleotide-HES complexes contained in the targeted oligonucleotide-HES conjugates can cross membranes in a receptor-independent manner and can deliver oligonucleotides to complementary sequences in the cytosol of live cells in vivo. The targeted oligonucleotide-HES conjugates have uses that include the targeted and/or localized delivery of antisense oligonucleotides, siRNAs, shRNAs, Dicer substrates, miRNAs, anti-miRNA, and other nucleic acid sequence in a living organism.

The present invention is directed to compounds of the formula (I), wherein all substituents are defined herein, as well as pharmaceutically acceptable compositions comprising compounds of the invention and methods of using said compositions in the treatment of various disorders. ##STR00001##

The present invention is directed to compounds of the formula (I), wherein all substituents are defined herein, as well as pharmaceutically acceptable compositions comprising compounds of the invention and methods of using said compositions in the treatment of various disorders. ##STR00001##

The present disclosure methods and kits for use of stimulator of interferon genes (STING) agonist compounds, such as cyclic dinucleotides, amidobenzimidazoles, and benzothiophenes, in the treatment and prevention of pain, such as neuropathic pain, inflammatory pain, and cancer pain. Combination therapies and pharmaceutical formulations for treating of pain are also described.