Novel compounds and methods for the inhibition of biological barrier permeability and for the inhibition of peptide translocation across biological barriers are identified. Assays for determining modulators of biological barrier permeability and for peptide translocation across biological barriers are provided. Methods for treating diseases relating to aberrant biological barrier permeability and peptide translocation across biological barriers are provided. Such diseases include celiac disease, necrotizing enterocolitis, diabetes, cancer, inflammatory bowel diseases, asthma, COPD, excessive or undesirable immune response, gluten sensitivity, gluten allergy, food allergy, rheumatoid arthritis, multiple sclerosis, immune-mediated or type 1 diabetes mellitus, systemic lupus erythematosus, psoriasis, scleroderma and autoimmune thyroid diseases.

The present disclosure relates to metal di-amino acid chelates and metal tri-amino acid chelates.

Provided herein are compounds that modulate the activity of inhibitor of apoptosis proteins (IAPs), compositions comprising the compounds, and methods of using the compounds and compositions comprising the compounds.

Described are compounds for targeting proteases, e.g. serine proteases and their use in the diagnostic methods and methods for treatment of respiratory diseases such as cystic fibrosis. The compounds have the structure [H]—[B]-[A]; wherein [H] is a hydrophilic group, [B] is a subsite recognition group and [A] is a binding group; wherein A has the formula: —C(0)—CH.sub.2—NR.sup.1—COOR.sup.2 and wherein [B] has the structure: (i) —[CO—CH.sub.2—NR.sup.3]m-, or (ii) -[AA1-AA2]- or (iii) -(AA1-C0-CH.sub.2NR.sup.3)— or (iv) —(CO—CH.sub.2—NR.sup.3-AA1)- or (v) —(C0—CH.sub.2—NR.sup.4-AA1-AA3)-.

Provided are peptoid-peptide macrocycles. The peptoid-peptide macrocycles may have inhibitory activity towards the Wnt signaling pathway. The Wnt signaling pathway is associated with cancer and other diseases and conditions. Such diseases include, for example, pulmonary fibrosis. Also described are methods of making the peptoid-peptide macrocycles, compositions containing the peptoid-peptide macrocycles, and methods of using the peptoid-peptide macrocycles.

Disclosed are proteasome inhibitors, fibroblast activation protein (FAP)-activated prodrugs of proteasome inhibitors, and pharmaceutically acceptable salts of the inhibitors and prodrugs. Also disclosed are related pharmaceutical compositions, and methods of using the inhibitors and prodrugs and compositions thereof, for example, in treating cancer or other cell proliferative diseases. In vitro and in vivo methods of quantifying the expression of FAP in a biopsy sample and a mammal, respectively, are also disclosed.

Novel inhibitors of IAP that are useful as therapeutic agents for treating malignancies and have the general formula I: ##STR00001##
wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and R.sup.6 are as described herein.

Pharmaceutical compositions of the invention include substituted riluzole prodrugs useful for the treatment of cancers including melanoma, breast cancer, brain cancer, and prostate cancer through the release of riluzole. Prodrugs of riluzole have enhanced stability to hepatic metabolism and are delivered into systemic circulation by oral administration, and then cleaved to release riluzole in the plasma via either an enzymatic or general biophysical release process.

Provided herein are tripeptide epoxy ketone protease inhibitors, methods of their preparation, related pharmaceutical compositions, and methods of using the same. For example, provided herein are compounds of Formula (X): ##STR00001##
and pharmaceutically acceptable salts and compositions including the same. The compounds and compositions provided herein may be used, for example, in the treatment of diseases including inflammation and neurodegenerative disease.

One aspect of the invention provides a composition of novel high penetration compositions (HPC) or a high penetration prodrug (HPP) for treatment of Parkinson's disease. The HPCs/HPPs are capable of being converted to parent active drugs or drug metabolites after crossing the biological barrier and thus can render treatments for the conditions that the parent drugs or metabolites can. Additionally, the HPPs are capable of reaching areas that parent drugs may not be able to access or to render a sufficient concentration at the target areas and therefore render novel treatments. The HPCs/HPPs can be administered to a subject through various administration routes, e.g., locally delivered to an action site of a condition with a high concentration or systematically administered to a biological subject and enter the general circulation with a faster rate.