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 present disclosure relates to compounds and a pharmaceutically acceptable salt thereof, compositions, combinations and medicaments containing the compounds, and processes for their preparation. The disclosure also relates to the use of the compounds, combinations, compositions and medicaments, for example as inhibitors of the activity of the estrogen receptor, including degrading the estrogen receptor, the treatment of diseases and conditions mediated by the estrogen receptor.

The present specification discloses tripartite androgen receptor eliminators (AREs), pharmaceutical compositions and medicaments comprising such AREs, methods and uses for such AREs and compositions and medicaments, and methods and uses for AREs and compositions and medicaments for treating an androgen receptor signaling-mediated condition, disease or disorder.

The disclosure features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers.

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.

Provided herein are phosphodiesterase 4 (PDE4) inhibitors, e.g., a compound of Formula (I) or (II), and pharmaceutical compositions thereof. Also provided herein are methods of their use for treating, preventing, or ameliorating one or more symptoms of a disease, disorder, or condition associated with PDE4 malfunction.

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Provided are a cyclic peptide compound simulating a natural product structure- and a method for preparation thereof. The method is: the compound of formula I, a divalent palladium catalyst, and a silver salt undergoing an intramolecular arylation in a solvent under heating and stirring to construct a cyclic peptide, to generate the compound of formula II, in which the arylation sites are diverse, and can be extended to the side chain γ-position methyl or methylene of the majority hydrophobic amino acids to perform intramolecular arylation, thus overcoming the previous defect of the restriction of the types of selectable amino acids, and effectively constructing a novel aromatic ring-supported cyclic peptide compound. The aromatic ring support structure can form a novel 3D structure similar to a natural product, and provide a very favorable support for the subsequent construction of a cyclic peptide molecular library and high-throughput drug screening.

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The present application is directed to cargo delivery complexes for intracellular delivery of a cargo molecule comprising: a first peptide comprising a cell-penetrating peptide (CPP), a second peptide comprising a cell-penetrating peptide, and a cargo molecule. The second peptide comprises a polyethylene glycol (PEG) moiety linked to the second CPP, and the first peptide does not have a PEG moiety. The present application is also directed to a cargo delivery complex comprising a CPP and a cargo molecule wherein the CPP is a retro-inverso peptide. The present application is also directed to a cargo delivery complex comprising a CPP and a cargo molecule wherein the peptide further comprises a targeting sequence selected from the group consisting of GYVSK, GYVS, YIGS and YIGSR. Methods of making and using the cargo delivery complexes are also disclosed.

This invention is in the field of medicinal pharmacology. In particular, the present invention relates to pharmaceutical agents which function as inhibitors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral replication and/or SARS-CoV-2 related viral 3CL protease (M.sup.pro) activity. The invention further relates to methods of treating and/or ameliorating symptoms related to conditions caused by the SARS-CoV-2 virus (e.g., COVID-19), comprising administering to a subject (e.g., a human patient) a composition comprising one or more pharmaceutical agents which function as inhibitors of SARS-CoV-2 viral replication and/or inhibitors of SARS-CoV-2 related M.sup.pro activity.