Provided herein are deuterated compounds and compositions useful in increasing PPARδ activity. The compounds have a formula ##STR00001##
where L.sup.5 comprises at least one deuterium. Exemplary species include ##STR00002##
The compounds and compositions provided herein are useful for the treatment of PPARδ related diseases (e.g., muscular diseases, vascular disease, demyelinating disease, and metabolic diseases).

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.

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.

The invention provides novel compounds having the general formula (I) ##STR00001##
wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.11 and R.sup.23 are as described herein, compositions including the compounds and methods of using the compounds.

The disclosure provides compounds having formula (I):

##STR00001##

and the pharmaceutically acceptable salts thereof, wherein R.sub.1, R.sub.2, R.sub.2′, and X are as defined as set firth in the specification. Compounds having formula (I) are prodrugs that release glutamine analogs, e.g., 6-diazo-5-oxo-L-norleucine (DON). The disclosure also provides compounds having formula (I) for use in treating cancer.

The present invention provides a method for constructing PROTAC by using double targets, and a specific construction method and application of a double-target. PROTAC constructed by using the method. The present invention proposes for the first time the concept of PROTAC with double-target design, namely, the Target protein I is degraded by PROTAC when a specific E3 is selected, meanwhile, the Target protein II is increased for the degradation of the E3 natural substrate protein is hindered due to the competition of PROTAC to E3. By using this method, the present invention constructs for the first time a double-target PROTAC which is capable of not only degrading Smad3 via target ubiquitination but also simultaneously up-regulating the HIF-α protein level, which theoretically plays the role of renal protection, such as anti-fibrosis and the treatment of renal anemia, via multi channels.

The present invention relates to TLR2 agonist compounds and their compositions, and the use of such compounds and compositions in the prevention and/or treatment of respiratory infections, or diseases or conditions associated with viral or bacterial infections.

Disclosed are a novel self-assembled amino acid supramolecular polymer, a preparation method therefor, and an application thereof. The self-assembled supramolecular polymer is N-lauroyl-L-alanyl-L-alanine or a salt thereof, and the salt thereof comprises sodium N-lauroyl-L-alanyl-L-alaninate and potassium N-lauroyl-L-alanyl-L-alaninate. The disclosed polymer is more effective at inhibiting bacteria and removing pesticides, and can be widely applied to the daily chemical, agricultural, and pharmaceutical industries. Further disclosed are three methods for preparing the compound. The methods produce products in high yields and are suitable for industrial production.

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.