The present invention relates to a class of N-cyanopyrrolidines with activity as inhibitors of the deubiquitylating enzyme USP30, having utility in a variety of therapeutic areas, including conditions involving mitochondrial dysfunction, cancer and fibrosis: Formula (I), Formula (II).

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Disclosed herein are small molecules that inhibit apoptosis and promote autophagy through the TRADD pathway, and their use for treatment of neurodegenerative diseases. Methods of preparing these small molecules and medicinal efficacy are described.

Provided herein are methods and pharmaceutical compositions related to the bacteria and microbial extracellular vesicles (mEVs) of Harryflintia acetispora that are useful as therapeutic agents.

The disclosure relates to in vivo and ex vivo uses of dihydronicotinamide riboside (NRH), dihydronicotinic acid riboside (NARH) and reduced derivatives thereof to treat immune-related disorders (e.g., systemic inflammatory response syndrome and sepsis), kidney disorders (e.g., acute kidney injury and hepatorenal syndrome [HRS]), liver disorders (e.g., acute liver failure and HRS), hemolytic disorders (e.g., hemolysis and hemolytic anemia), and disorders and conditions associated with oxidative stress, damage or injury (e.g., methemoglobinemia and anemia). NRH, NARH and reduced derivatives thereof can be used in vivo or ex vivo alone or in combination with one or more additional therapeutic agents, such as an anti-inflammatory agent or/and an antioxidant.

Herein is reported an anti-transferrin receptor antibody that specifically binds to human transferrin receptor and cynomolgus transferrin receptor, which comprises i) a humanized heavy chain variable domain derived from the heavy chain variable domain of SEQ ID NO: 01, and ii) a humanized light chain variable domain derived from the light chain variable domain of SEQ ID NO: 26, wherein the antibody has an off-rate for the human transferrin receptor that is equal to or less than (i.e. at most) the off-rate of the anti-transferrin receptor antibody 128.1 for the cynomolgus transferrin receptor, whereby the off-rates are determined by surface plasmon resonance, and whereby the anti-transferrin receptor antibody 128.1 has a heavy chain variable domain of SEQ ID NO: 64 and a light chain variable domain of SEQ ID NO: 65.

A compound of Formula I, ##STR00001##
and its analogs are provided. Compositions that include Formula I can be used to inhibit human equilibrative nucleoside transporter 1, increase adenosine signaling and produce effects that include increasing antiviral activity, increasing antiparasitic activity, increasing alcohol tolerance, decreasing pain protecting from ischemia as well as many other conditions.

S100A8-inhibiting peptides include (A) a peptide of 5 to 10 residues in length containing a fifth alanine (Ala) from an N-terminus in an amino acid sequence of SEQ ID NO: 1, or (B) a peptide consisting of an amino acid sequence of SEQ ID NO: 2.

The inventive compounds are small molecule therapeutics that are potent inhibitors of USP7 activity. The invention also provides pharmaceutical compositions comprising the compounds, and methods for using the compounds for treating or preventing a disease, disorder, or condition associated with USP7 activity.

Compositions and methods for delivering a therapeutic protein to the central nervous system (CNS), in order to treat diseases and disorders that impair the CNS, such as treating lysosomal storage diseases, are disclosed. Therapeutic proteins delivered via a therapeutically effective amount of a nucleotide composition encoding the therapeutic protein conjugated to a cell surface receptor-binding protein, e.g., anti-TfRCscfv:GAA, that crosses the blood brain barrier (BBB) are provided.

Methods of treating anti-inflammatory conditions through the use of boron-containing small molecules are disclosed.