Unique compounds useful for inhibiting a proteasome in a cell, pharmaceutical compositions and methods of their use are provided herein.

The present invention relates to use of peptides as a therapeutic agent, wherein it has been confirmed that the peptides of the present invention significantly inhibit the activity of T cells and the differentiation of T helper 17 cells (Th17 cells), which are associated with autoimmune disease, and have remarkable effects of treating and improving arthritis in an animal model of arthritis. Therefore, the peptides may be used as an active ingredient in therapeutic agents for various autoimmune diseases such as bone disease, inflammatory disease or rheumatoid arthritis.

Compounds of Formula (I)a or (I)b: ##STR00001##
including certain quinone derivatives, and the corresponding pharmaceutical compositions, which may serve to modulate ferroptosis in a subject. Also disclosed herein are the preparations of these compounds and pharmaceutical compositions and their potential uses in the manufacture of a medicament in reducing reactive oxygen species (ROS) in a cell and for preventing, treating, ameliorating certain related disorder or a disease.

Provided are compounds useful for selectively inhibiting HSP70 isoforms. Also provided are methods of inhibiting HSP70 proteins and methods of treating a disease characterized by overexpression of a HSP70, such as cancer. In particular embodiments, the disclosed compounds may be used as potent inhibitors for HSPA5 and may display greater than 20-fold selectivity over other HSP70 isoforms.

The present invention relates to use of peptides as a therapeutic agent, wherein it has been confirmed that the peptides of the present invention significantly inhibit the activity of T cells and the differentiation of T helper 17 cells (Th17 cells), which are associated with autoimmune disease, and have remarkable effects of treating and improving arthritis in an animal model of arthritis. Therefore, the peptides may be used as an active ingredient in therapeutic agents for various autoimmune diseases such as bone disease, inflammatory disease or rheumatoid arthritis.

The photolabile hydrazine linker of the present invention is based on the o-nitro-veratryl group, which is capable of releasing hydrazide derivatives upon UV irradiation. The linker allows for a new solid-phase peptide synthesis (SPPS) strategy which is fully orthogonal to the most commonly used protecting groups and chemical methods in SPPS and shows excellent compatibility with peptide composition, notably the 20 naturally occurring α-amino acid residues (even in their side-chain protected form) are accepted in the C-terminal of the peptide hydrazides. Furthermore, the linker unit can be applied to synthesize combinatorial libraries of biological interesting heterocyclic compounds, such as pyranopyrazoles.

One aspect of the invention provides a composition of novel high penetration compositions (HPC) or a high penetration prodrug (HPP) for treatment of Parkinson's disease. The HPCs/HPPs are capable of being converted to parent active drugs or drug metabolites after crossing the biological barrier and thus can render treatments for the conditions that the parent drugs or metabolites can. Additionally, the HPPs are capable of reaching areas that parent drugs may not be able to access or to render a sufficient concentration at the target areas and therefore render novel treatments. The HPCs/HPPs can be administered to a subject through various administration routes, e.g., locally delivered to an action site of a condition with a high concentration or systematically administered to a biological subject and enter the general circulation with a faster rate.

The present invention discloses compounds of Formula (I), and pharmaceutically acceptable salts, thereof:

##STR00001##

which inhibit coronavirus replication activity. The invention further relates to pharmaceutical compositions comprising a compound of Formula (I) or a pharmaceutically acceptable slat thereof, and methods of treating or preventing a coronavirus infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof.

The methods and compositions described herein relate, in part, to the generation of a synthetic degradation system in E. coli that provides tunable control of the protein level of targeted genes by using components of the Mesoplasma florum tmRNA system. Provided herein are degradation tag variants that permit independent control of both the initial level and inducible degradation rate of attached proteins.

One aspect of the invention provides a composition of novel high penetration compositions (HPC) or a high penetration prodrug (HPP) for treatment of Parkinson's disease. The HPCs/HPPs are capable of being converted to parent active drugs or drug metabolites after crossing the biological barrier and thus can render treatments for the conditions that the parent drugs or metabolites can. Additionally, the HPPs are capable of reaching areas that parent drugs may not be able to access or to render a sufficient concentration at the target areas and therefore render novel treatments. The HPCs/HPPs can be administered to a subject through various administration routes, e.g., locally delivered to an action site of a condition with a high concentration or systematically administered to a biological subject and enter the general circulation with a faster rate.