This invention is related to the field of PCSK9 biology and the composition and methods of use of small molecule ligands for modulation of PCSK9 biological activity. In particular, the invention provides compositions of small molecule compounds that modulate circulating levels of low density lipoproteins by altering the conformation of the protein PCSK9. Binding these small molecule ligands to PCSK9 alters the conformation of the protein, modifying the interaction between PCSK9 and an endogenous low density lipoprotein receptor, and can lead to reduced or increased levels of circulating LDL-cholesterol. High LDL cholesterol levels are associated with increased risk for heart disease. Low LDL-cholesterol levels may be problematic in other conditions, such as liver dysfunction; thus, there is also utility for small molecule ligands that can raise LDL levels.

Disclosed herein are inhibitors of the GGDPS enzyme, and methods for their use in treating or preventing diseases, such as multiple myeloma. The inhibitors described herein can include compounds of Formula (I) and pharmaceutically acceptable salts thereof: ##STR00001##
wherein the substituents are described.

Disclosed herein are inhibitors of the GGDPS enzyme, and methods for their use in treating or preventing diseases, such as multiple myeloma. The inhibitors described herein can include compounds of Formula (I) and pharmaceutically acceptable salts thereof: ##STR00001##
wherein the substituents are described.

This invention is related to the field of PCSK9 biology and the composition and methods of use of small molecule ligands for modulation of PCSK9 biological activity. In particular, the invention provides compositions of small molecule compounds that modulate circulating levels of low density lipoproteins by altering the conformation of the protein PCSK9. Binding these small molecule ligands to PCSK9 alters the conformation of the protein, modifying the interaction between PCSK9 and an endogenous low density lipoprotein receptor, and can lead to reduced or increased levels of circulating LDL-cholesterol. High LDL-cholesterol levels are associated with increased risk for heart disease. Low LDL-cholesterol levels may be problematic in other conditions, such as liver dysfunction; thus, there is also utility for small molecule ligands that can raise LDL levels.

This invention is related to the field of PCSK9 biology and the composition and methods of use of small molecule ligands for modulation of PCSK9 biological activity. In particular, the invention provides compositions of small molecule compounds that modulate circulating levels of low density lipoproteins by altering the conformation of the protein PCSK9. Binding these small molecule ligands to PCSK9 alters the conformation of the protein, modifying the interaction between PCSK9 and an endogenous low density lipoprotein receptor, and can lead to reduced or increased levels of circulating LDL-cholesterol. High LDL-cholesterol levels are associated with increased risk for heart disease. Low LDL-cholesterol levels may be problematic in other conditions, such as liver dysfunction; thus, there is also utility for small molecule ligands that can raise LDL levels.

Disclosed are novel conjugates and methods for the preparation thereof. One of the methods for the preparation of a conjugate comprises a step of: acting a compound of formula (I), with a thiol-containing molecule of formula (II), wherein represents an amino acid, a peptide, a protein, an antibody, a nucleotide, an oligonucleotide, a saccharide, a polysaccharide, a polymer, a small molecule, an optionally substituted C.sub.1-C.sub.8-alkyl, an optionally substituted phenyl, or an optionally substituted aromatic 5- or 6-membered heterocyclic system; resulting in a compound of formula (III).

Disclosed are novel conjugates and methods for the preparation thereof. One of the methods for the preparation of a conjugate comprises a step of: acting a compound of formula (I), with a thiol-containing molecule of formula (II), wherein represents an amino acid, a peptide, a protein, an antibody, a nucleotide, an oligonucleotide, a saccharide, a polysaccharide, a polymer, a small molecule, an optionally substituted C.sub.1-C.sub.8-alkyl, an optionally substituted phenyl, or an optionally substituted aromatic 5- or 6-membered heterocyclic system; resulting in a compound of formula (III).

The present disclosure provides phosphonate-containing heterocycle compounds with TYK2 kinase inhibitory activity, pharmaceutical compositions comprising the same, and applications thereof. The present disclosure provides compounds of Formula (I), as inhibitors of TYK2 kinase. These compounds can be used for preventing and/or treating TYK2 kinase-related diseases and/or conditions.

##STR00001##

The present invention relates to novel compounds and probes which have a common chemical structure necessary to obtain potent inhibitory activity against KLK4 and/or may be used for the detection of KLK4 peptides and their activity. It further relates to the use of these compounds and methods for inhibiting and/or detecting KLK4 activity in vitro and in vivo by making use of said probes or inhibitors. The compounds of the invention differ from prior art compounds at least in the presence of phenyl guanidine (instead of e.g. benzyl guanidine) and/or the presence of a heteroatom in the tail group, their combined presence unexpectedly leading to potent and selective KLK4 inhibitory activity.

Described is a targeted molecular scaffold for construction of a metabolic inhibitor loaded with cancer-cell specific activity and anti-tumor immunity. Incorporation of a mitochondria targeting moiety such as triphenylphosphonium cation through a biodegradable linker in allowed for mitochondria targeting of certain metabolic inhibitors like dichloroacetic acid (DCA).