The present invention relates to bifunctional Proteolysis Targeting Chimeric ligands (Protac compounds) comprising a ligase modulator/binder and a molecule that binds to a protein target of interest, and methods of treating various diseases and conditions with the Protac compounds, including diseases associated with androgen receptors.

The present invention relates to a kinase inhibitor, comprising a compound of Formula I or a pharmaceutically acceptable salt, solvate, ester, acid, metabolite or prodrug thereof. The present invention also relates to a pharmaceutical composition comprising the kinase inhibitor, and to uses and methods for using these compounds and compositions to inhibit the activity of wild-type FLT3, mutant FLT3-ITD, PDGFRα and/or PDGFRβ kinase in a cell or a subject, as well as uses and methods of these compounds and compositions to preventing or treating kinase-associated conditions in a subject. ##STR00001##

The present invention relates to a kinase inhibitor, comprising a compound of Formula I or a pharmaceutically acceptable salt, solvate, ester, acid, metabolite or prodrug thereof. The present invention also relates to a pharmaceutical composition comprising the kinase inhibitor, and to uses and methods for using these compounds and compositions to inhibit the activity of wild-type FLT3, mutant FLT3-ITD, PDGFRα and/or PDGFRβ kinase in a cell or a subject, as well as uses and methods of these compounds and compositions to preventing or treating kinase-associated conditions in a subject. ##STR00001##

Provided herein are methods of treating diseases, including cancer, with ULK inhibitors, both as monotherapies and in combination with other therapeutic agents.

The present subject matter provides a crystalline form of the compound having the following structure: ##STR00001##
wherein the crystalline form is a polymorph, hydrate or solvate.

The present subject matter provides a crystalline form of the compound having the following structure: ##STR00001##
wherein the crystalline form is a polymorph, hydrate or solvate.

Disclosed herein are dihydroceramide desaturase 1 (Des1) inhibitor compounds and compositions, which are useful in the treatment of diseases, such as metabolic disorders, where inhibition of Des1 is expected to be therapeutic to a patient. Methods of inhibition of Des1 activity in a human or animal subject are also provided.

Provided herein are opioid receptor modulators and pharmaceutical compositions comprising said compounds.

The present disclosure is concerned with 2-pyrimidone compounds that are capable of inhibiting a viral infection and methods of treating alphavirus viral infections such as, for example, chikungunya, Eastern equine encephalitis (EEEV), Western equine encephalitis (WEEV), and Venezuelan equine encephalitis using these compounds. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Compounds having activity as inhibitors of LRRK2 kinase are provided. The compounds have Structure (I):

##STR00001##

or a pharmaceutically acceptable salt, stereoisomer or prodrug thereof, wherein A, B, R.sup.1a, R.sup.1b, R.sup.2 and L are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of LRRK2 kinase are also provided.