The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of CRBN, and the treatment of CRBN-mediated disorders.

The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of CRBN, and the treatment of CRBN-mediated disorders.

The disclosure features novel lipids and compositions involving the same. Lipid nanoparticles (e.g., empty LNPs or loaded LNPs) include a novel lipid as well as additional lipids such as phospholipids, structural lipids, and PEG lipids. Lipid nanoparticles (e.g., empty LNPs or loaded LNPs) further including therapeutic and/or prophylactics such as RNA are useful in the delivery of therapeutic and/or prophylactics to mammalian cells or organs to, for example, regulate polypeptide, protein, or gene expression.

The disclosure features novel lipids and compositions involving the same. Lipid nanoparticles (e.g., empty LNPs or loaded LNPs) include a novel lipid as well as additional lipids such as phospholipids, structural lipids, and PEG lipids. Lipid nanoparticles (e.g., empty LNPs or loaded LNPs) further including therapeutic and/or prophylactics such as RNA are useful in the delivery of therapeutic and/or prophylactics to mammalian cells or organs to, for example, regulate polypeptide, protein, or gene expression.

A class of bifunctional compounds for targeting and degrading an IRAK4 kinase protein, a pharmaceutical composition and a preparation method therefor are provided. The compounds not only effectively inhibits and/or degrades the IRAK4 kinase protein in cells, but also effectively inhibit the production of IL-6 by immune cells, and has good degradation selectivity. The compounds can be used in the preparation of a drug for treating and/or preventing IRAK4-mediated related diseases or conditions, such as cancer, immunological diseases and inflammatory diseases.

A class of bifunctional compounds for targeting and degrading an IRAK4 kinase protein, a pharmaceutical composition and a preparation method therefor are provided. The compounds not only effectively inhibits and/or degrades the IRAK4 kinase protein in cells, but also effectively inhibit the production of IL-6 by immune cells, and has good degradation selectivity. The compounds can be used in the preparation of a drug for treating and/or preventing IRAK4-mediated related diseases or conditions, such as cancer, immunological diseases and inflammatory diseases.

Disclosed are small molecules against cereblon to enhance effector T cell function. Methodos of making thes molecules and methods of using them to treat various disease states are also disclosed.

The invention described herein relates to certain pyrimidinetrione N-substituted glycine derivatives of formula (I)

##STR00001##

which are antagonists of HIF prolyl hydroxylases and are useful for treating diseases benefiting from the inhibition of this enzyme, anemia being one example.

The invention described herein relates to certain pyrimidinetrione N-substituted glycine derivatives of formula (I)

##STR00001##

which are antagonists of HIF prolyl hydroxylases and are useful for treating diseases benefiting from the inhibition of this enzyme, anemia being one example.

The invention relates to pyrimidinone derivatives of the general Formula I, ##STR00001## or a pharmaceutically acceptable salt thereof, and the use of the compounds of the present invention for the treatment of hyperproliferative diseases and disorders in mammals, especially humans, and pharmaceutical compositions containing such compound.