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

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.

The present invention relates to a bifunctional compound, a preparation method therefor, and a use thereof, wherein the bifunctional compound comprises an E3 ubiquitin ligase-binding moiety; a target protein-binding moiety that binds to an androgen receptor; and a linking moiety that links the E3 ubiquitin ligase-binding moiety and the target protein-binding moiety. The bifunctional compound of the present application allows the androgen receptor to be positioned adjacent to the ubiquitin ligase, so as to achieve the degradation or inhibition of the androgen receptor.

The invention provides novel classes of HCV therapeutics that are orally available, safe and effective HCV NS3/4A protease inhibitors and are less susceptible to drug resistance than existing therapeutics. The invention also relates to pharmaceutical composition of these compounds and methods of preparation and use thereof.

The purpose of the present invention is to provide an adhesion prevention material capable of exhibiting excellent adhesion preventive effect. This adhesion prevention material concurrently uses: (A) a peptide (A-1) having an amino acid sequence-(X-Pro-Y)n-[wherein X represents an arbitrary defined amino acid, Pro represents proline, Y represents hydroxyproline or proline, and n is an integer between 1 and 10] and/or a peptide (A-2) having an amino acid sequence-(Pro-Y)m-[wherein Pro represents proline, Y represents hydroxyproline or proline, and m is an integer between 1-10]; and (B) a gelatin gel. This adhesion prevention material exhibits a dramatically enhanced adhesion preventive effect as compared with the case where the abovementioned components are used individually, and in particular, has a markedly superior effect against adhesion of tendons.

Provided is a novel fluorescent probe which can be used in a spray manner, has an outstandingly high sensitivity-specificity with instantaneousness, and enables detection of a brain tumor.

A fluorescent probe for detecting a brain tumor, including a compound of the following formula (I) or a salt thereof:

##STR00001##

wherein P1 represents an arginine residue, a histidine residue or a tyrosine residue, P2 represents a proline residue or a glycine residue, where P1 is linked to an adjacent N atom by forming an amide bond, and P2 is linked to P1 by forming an amide bond; R.sup.1 represents a hydrogen atom, or 1 to 4 identical or different substituents each independently selected from the group consisting of an optionally substituted alkyl group, a carboxyl group, an ester group, an alkoxy group, an amide group and an azide group; R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 each independently represent a hydrogen atom, a hydroxyl group, an optionally substituted alkyl group or a halogen atom; R.sup.8 and R.sup.9 each independently represent a hydrogen atom or an alkyl group;

X represents O, Si(R.sup.a)(R.sup.b), Ge(R.sup.a)(R.sup.b), Sn(R.sup.a)(R.sup.b), C(R.sup.a) (R.sup.b) or P(═O)(R.sup.a); R.sup.a and R.sup.b each independently represent a hydrogen atom, an alkyl group or an aryl group; and Y represents a C.sub.1-C.sub.3 alkylene group.

The invention provides novel classes of HCV therapeutics that are orally available, safe and effective HCV NS3/4A protease inhibitors and are less susceptible to drug resistance than existing therapeutics. The invention also relates to pharmaceutical composition of these compounds and methods of preparation and use thereof. ##STR00001##

The present disclosure relates to bifunctional compounds, which find utility as modulators of estrogen receptor (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end at least one of a Von Hippel-Lindau ligand, a cereblon ligand, inhibitors of apoptosis proteins ligand, mouse double-minute homolog 2 ligand, or a combination thereof, 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 provides a catalyst containing a Brønsted acid as a novel means capable of producing an amide compound by highly stereoselectively and/or highly efficiently causing an amidation reaction in a variety of substrates having a carboxylic ester group and an amino group.

Compounds, pharmaceutical compositions, methods and kits are described for treating or preventing neurodegenerative diseases such as Alzheimer's disease.