Cryptosporidium parvum is a highly prevalent zoonotic and anthroponotic protozoan parasite that causes a diarrheal syndrome in children and neonatal livestock, culminating in growth retardation and mortalities. Disclosed herein are inhibitors against the enzymatic activity of recombinant CpLDH protein that were identified. The inhibitors were tested for anti-Cryptosporidium effect using in vitro infection assays of HCT-8 cells monolayers. Compounds NSC158011 and NSC10447 were identified to inhibit the proliferation of intracellular C. parvum in vitro, with IC50 values of 14.88 and 72.65 μM, respectively. At doses tolerable in mice, both NSC158011 and NSC10447 significantly reduced the shedding of C. parvum oocysts in infected immunocompromised mice's feces and prevented intestinal villous atrophy as well as mucosal erosion due to C. parvum. These findings have unveiled anti-Cryptosporidium drug candidates that can be explored further for the development of therapeutic agents against C. parvum infections.

Cryptosporidium parvum is a highly prevalent zoonotic and anthroponotic protozoan parasite that causes a diarrheal syndrome in children and neonatal livestock, culminating in growth retardation and mortalities. Disclosed herein are inhibitors against the enzymatic activity of recombinant CpLDH protein that were identified. The inhibitors were tested for anti-Cryptosporidium effect using in vitro infection assays of HCT-8 cells monolayers. Compounds NSC158011 and NSC10447 were identified to inhibit the proliferation of intracellular C. parvum in vitro, with IC50 values of 14.88 and 72.65 μM, respectively. At doses tolerable in mice, both NSC158011 and NSC10447 significantly reduced the shedding of C. parvum oocysts in infected immunocompromised mice's feces and prevented intestinal villous atrophy as well as mucosal erosion due to C. parvum. These findings have unveiled anti-Cryptosporidium drug candidates that can be explored further for the development of therapeutic agents against C. parvum infections.

The present application provides malonamide compounds, and derivatives thereof (e.g., N-aryl malonamides (NAM), acetamides, oxalamides, and the like), that are useful, for example, for the treatment of acute, chronic/persistent, and/or relapsing infections. Pharmaceutical compositions, methods of treating diseases (e.g., bacterial infections), and methods of reducing bacterial virulence are also provided.

The present application provides malonamide compounds, and derivatives thereof (e.g., N-aryl malonamides (NAM), acetamides, oxalamides, and the like), that are useful, for example, for the treatment of acute, chronic/persistent, and/or relapsing infections. Pharmaceutical compositions, methods of treating diseases (e.g., bacterial infections), and methods of reducing bacterial virulence are also provided.

This invention provides 1-pyridyl pyrazole amide compounds represented by Formula (I) and preparation and uses thereof, wherein each substituent is defined in the disclosure. The compounds of Formula (I) of this invention possess excellent insecticidal activities, especially very strong activities against pests such as aphids, armyworms and diamondback moths, etc., and can be used to control various pests. This invention also provides synthetic intermediates represented by Formula (II) for preparing compounds of Formula (I) wherein each substituent is defined in the specification.

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Provided herein are compositions and methods for generating polypeptides using non-natural amino acids (nnAAs) and genetic machinery, wherein the modified polypeptides, such as therapeutic polypeptides, bind to albumin, such as serum albumin. Methods of substituting a non-natural amino acid in a first polypeptide to obtain a modified polypeptide, the nnAA in some instances comprising an albumin targeting group, are disclosed, as are methods for making populations of such modified polypeptides. A therapeutic polypeptide, interleukin-1 receptor antagonist (IL-1RA) is exemplified using the disclosed methods.

Provided herein are compositions and methods for generating polypeptides using non-natural amino acids (nnAAs) and genetic machinery, wherein the modified polypeptides, such as therapeutic polypeptides, bind to albumin, such as serum albumin. Methods of substituting a non-natural amino acid in a first polypeptide to obtain a modified polypeptide, the nnAA in some instances comprising an albumin targeting group, are disclosed, as are methods for making populations of such modified polypeptides. A therapeutic polypeptide, interleukin-1 receptor antagonist (IL-1RA) is exemplified using the disclosed methods.

Provided herein are compositions and methods for generating polypeptides using non-natural amino acids (nnAAs) and genetic machinery, wherein the modified polypeptides, such as therapeutic polypeptides, bind to albumin, such as serum albumin. Methods of substituting a non-natural amino acid in a first polypeptide to obtain a modified polypeptide, the nnAA in some instances comprising an albumin targeting group, are disclosed, as are methods for making populations of such modified polypeptides. A therapeutic polypeptide, interleukin-1 receptor antagonist (IL-1RA) is exemplified using the disclosed methods.

Provided herein are compositions and methods for generating polypeptides using non-natural amino acids (nnAAs) and genetic machinery, wherein the modified polypeptides, such as therapeutic polypeptides, bind to albumin, such as serum albumin. Methods of substituting a non-natural amino acid in a first polypeptide to obtain a modified polypeptide, the nnAA in some instances comprising an albumin targeting group, are disclosed, as are methods for making populations of such modified polypeptides. A therapeutic polypeptide, interleukin-1 receptor antagonist (IL-1RA) is exemplified using the disclosed methods.

The present application provides malonamide compounds, and derivatives thereof (e.g., N-aryl malonamides (NAM), acetamides, oxalamides, and the like), that are useful, for example, for the treatment of acute, chronic/persistent, and/or relapsing infections. Pharmaceutical compositions, methods of treating diseases (e.g., bacterial infections), and methods of reducing bacterial virulence are also provided.