Disclosed is to a new pharmaceutical composition for oral administration containing sulfasalazine and/or a sulfasalazine organic salt, production processes and uses, in particular in the treatment of a disease or condition in which modulation of inflammatory cells is beneficial, a disease or condition concerning bones or joints and/or the gastro-intestinal tract.

Phosphonium-based ionic conjugates (PBICs) are described. The PBICs each include a cationic binding partner comprising a phosphonium ion and an anionic binding partner comprising a pharmaceutically active compound, or prodrug, or derivative thereof. The conjugate can have at least one enhanced physiochemical, pharmacokinetic and/or therapeutic quality as compared to the pharmaceutically active compound when not provided in a PBIC. The phosphonium-containing cationic binding partner can also serve to enhance delivery of the anionic binding partner to the cytosol and/or the inner mitochondrial space. Methods of preparing the PBICs and using the PBICs to treat disease are also described.

Phosphonium-based ionic conjugates (PBICs) are described. The PBICs each include a cationic binding partner comprising a phosphonium ion and an anionic binding partner comprising a pharmaceutically active compound, or prodrug, or derivative thereof. The conjugate can have at least one enhanced physiochemical, pharmacokinetic and/or therapeutic quality as compared to the pharmaceutically active compound when not provided in a PBIC. The phosphonium-containing cationic binding partner can also serve to enhance delivery of the anionic binding partner to the cytosol and/or the inner mitochondrial space. Methods of preparing the PBICs and using the PBICs to treat disease are also described.

The disclosure provides methods of modulating an immune response by inhibiting BFL1, and related methods for treating and preventing diseases and disorders characterized by inflammation, especially neutrophil induced inflammation.

The disclosure provides methods of modulating an immune response by inhibiting BFL1, and related methods for treating and preventing diseases and disorders characterized by inflammation, especially neutrophil induced inflammation.

Therapeutics and methods of treating COVID-19 in a patient in need thereof comprising administering a pharmaceutically effective dose of a therapeutic, wherein the therapeutic contains an ACE2 externalizer, and the ACE2 externalizer is one of diminazene, diminazene aceturate, or a pharmaceutically acceptable salt, solvate, ester, amide, clathrate, stereoisomer, enantiomer, or prodrug thereof.

Therapeutics and methods of treating COVID-19 in a patient in need thereof comprising administering a pharmaceutically effective dose of a therapeutic, wherein the therapeutic contains an ACE2 externalizer, and the ACE2 externalizer is one of diminazene, diminazene aceturate, or a pharmaceutically acceptable salt, solvate, ester, amide, clathrate, stereoisomer, enantiomer, or prodrug thereof.

The inventors have found that compounds of formula (I) have an effect to protect cartilage. Accordingly the disclosure provides a pharmaceutical composition for protecting cartilage comprising a compound of formula (I) or an ester, oxide, pharmaceutically acceptable salt, or solvate thereof. The pharmaceutical composition can be used for treating and/or preventing a disease associated with cartilage degeneration such as osteoarthritis.

The inventors have found that compounds of formula (I) have an effect to protect cartilage. Accordingly the disclosure provides a pharmaceutical composition for protecting cartilage comprising a compound of formula (I) or an ester, oxide, pharmaceutically acceptable salt, or solvate thereof. The pharmaceutical composition can be used for treating and/or preventing a disease associated with cartilage degeneration such as osteoarthritis.

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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