Compounds of formulae (I) and (II), compositions, and methods for use in inhibiting the E3 enzyme Cbl-b in the ubiquitin proteasome pathway are disclosed. The compounds, compositions, and methods can be used to modulate the immune system, to treat diseases amenable to immune system modulation, and for treatment of cells in vivo, in vitro, or ex vivo.

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Compounds of formulae (I) and (II), compositions, and methods for use in inhibiting the E3 enzyme Cbl-b in the ubiquitin proteasome pathway are disclosed. The compounds, compositions, and methods can be used to modulate the immune system, to treat diseases amenable to immune system modulation, and for treatment of cells in vivo, in vitro, or ex vivo.

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Provided are methods of treating a disease or condition characterized by a deficiency of or a defect in an iron transporter using a small molecule. For example, the method may increase transepithelial iron transport, or it may increase iron release. Additionally, the small molecule may be hinokitiol, or it may be selected from the group consisting of amphotericin B, calcimycin, nonactin, deferiprone, purpurogallin, and maltol. Also provided is a method of identifying a compound capable of treating a disease or condition characterized by a deficiency of or a defect in an iron transporter.

Provided are methods of treating a disease or condition characterized by a deficiency of or a defect in an iron transporter using a small molecule. For example, the method may increase transepithelial iron transport, or it may increase iron release. Additionally, the small molecule may be hinokitiol, or it may be selected from the group consisting of amphotericin B, calcimycin, nonactin, deferiprone, purpurogallin, and maltol. Also provided is a method of identifying a compound capable of treating a disease or condition characterized by a deficiency of or a defect in an iron transporter.

The present disclosure relates to bifunctional compounds, which find utility as modulators of enhancer of zeste homolog 2 (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

The present disclosure relates to bifunctional compounds, which find utility as modulators of enhancer of zeste homolog 2 (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

The present invention relates to novel compounds of formula (I) and pharmaceutical compositions containing these compounds. The compounds provided herein can act as prostaglandin E2 (PGE2) EP4 receptor antagonists, which renders them highly advantageous for use in therapy, particularly in the treatment or prevention of cancer, a neovascular eye disease, inflammatory pain, or an inflammatory disease, such as, e.g., multiple sclerosis, rheumatoid arthritis or endometriosis.

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The present invention relates to novel compounds of formula (I) and pharmaceutical compositions containing these compounds. The compounds provided herein can act as prostaglandin E2 (PGE2) EP4 receptor antagonists, which renders them highly advantageous for use in therapy, particularly in the treatment or prevention of cancer, a neovascular eye disease, inflammatory pain, or an inflammatory disease, such as, e.g., multiple sclerosis, rheumatoid arthritis or endometriosis.

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The present invention is related to a supplement for reversing the aging of muscle cells after an acute bout of squat exercise in a subject, which comprises, or consists essentially of, or consists of, (1) Panax ginseng extract or Panax notoginseng extract or a combination thereof and (2) Rosa roxburghii extract at an amount to reverse the aging of muscle cells in a subject after after an acute bout of squat exercise. Provided in the present invention are the method and use of the supplement Rg1 for reversing the aging of muscle cells in a subject after an acute bout of squat exercise.

The present invention is related to a supplement for reversing the aging of muscle cells after an acute bout of squat exercise in a subject, which comprises, or consists essentially of, or consists of, (1) Panax ginseng extract or Panax notoginseng extract or a combination thereof and (2) Rosa roxburghii extract at an amount to reverse the aging of muscle cells in a subject after after an acute bout of squat exercise. Provided in the present invention are the method and use of the supplement Rg1 for reversing the aging of muscle cells in a subject after an acute bout of squat exercise.