The present invention provides aminopyrimidinylaminobenzonitrile compounds that inhibit the activity of never in mitosis gene A-related kinase 2 (NEK2) and are useful in the treatment of diseases related to activity of NEK2, including cancer (e.g., multiple myeloma, and breast, liver, pancreatic and colorectal cancers).

The present invention provides aminopyrimidinylaminobenzonitrile compounds that inhibit the activity of never in mitosis gene A-related kinase 2 (NEK2) and are useful in the treatment of diseases related to activity of NEK2, including cancer (e.g., multiple myeloma, and breast, liver, pancreatic and colorectal cancers).

The present disclosure provides compounds and methods useful for inhibiting SARM1 and/or treating and/or preventing axonal degeneration.

Methods are provided for modulating MRGPRX2 generally, or for treating a MRGPRX2 dependent condition more specifically, by contacting the MRGPRX2 or administering to a subject in need thereof, respectively, an effective amount of a compound having structure (I):

##STR00001##

or a pharmaceutically acceptable salt, isomer, hydrate, solvate or isotope thereof, wherein D, W, Z, R.sup.1, R.sup.2 and R.sup.3 are as defined herein. Pharmaceutical compositions containing such compounds, as well as the compounds themselves, are also provided.

Methods are provided for modulating MRGPRX2 generally, or for treating a MRGPRX2 dependent condition more specifically, by contacting the MRGPRX2 or administering to a subject in need thereof, respectively, an effective amount of a compound having structure (I):

##STR00001##

or a pharmaceutically acceptable salt, isomer, hydrate, solvate or isotope thereof, wherein D, W, Z, R.sup.1, R.sup.2 and R.sup.3 are as defined herein. Pharmaceutical compositions containing such compounds, as well as the compounds themselves, are also provided.

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##

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

A cyano-substituted pyridine and cyano-substituted pyrimidine compound and a preparation method therefor and an application thereof, which specifically relate to a compound represented by formula (I) and an isomer, a hydrate, a solvate, a pharmaceutically acceptable salt, and a prodrug thereof, and a preparation method therefor and an application thereof in the preparation of a drug as a kinase inhibitor. The compound has good inhibitory activity against kinases such as FGFR4 and mutant FGFR4.sup.V550L.

##STR00001##

A cyano-substituted pyridine and cyano-substituted pyrimidine compound and a preparation method therefor and an application thereof, which specifically relate to a compound represented by formula (I) and an isomer, a hydrate, a solvate, a pharmaceutically acceptable salt, and a prodrug thereof, and a preparation method therefor and an application thereof in the preparation of a drug as a kinase inhibitor. The compound has good inhibitory activity against kinases such as FGFR4 and mutant FGFR4.sup.V550L.

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