Abstract: Compounds having activity as inhibitors of NEK7 are provided. The compounds have Structure (I): or a stereoisomer, tautomer, or salt thereof, wherein A, W, X, Y, Z, R1, and R2 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 the NLRP3 inflammasome are also provided.

Abstract: Compounds having activity as inhibitors of LRRK2 kinase are provided. The compounds have Structure (I): or a pharmaceutically acceptable salt, stereoisomer or prodrug thereof, wherein A, B, R1a, R1b, R2, 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.

Abstract: Compounds having activity as inhibitors of NEK7 are provided. The compounds have Structure (I): or a pharmaceutically acceptable salt, stereoisomer or prodrug thereof, wherein, A, X, Y, R1, R2, R3, R4 and R5 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 the NLRP3 inflammasome are also provided.

Abstract: Compounds having activity as inhibitors of NEK7 are provided. The compounds have Structure (I): or a pharmaceutically acceptable salt, stereoisomer or prodrug thereof, wherein, A, X, Y, R1, R2, R3, R4 and R5 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 the NLRP3 inflammasome are also provided.

Abstract: Compositions comprising at least one NEK7 protein and a NEK7 small molecule inhibitor compound comprising at least one of the following features: (i) a hinge-binding element comprising at least one hydrogen donor and at least one hydrogen acceptor, (ii) a flexible linker, (iii) a urea linker, or (iv) a hydrophobic back pocket group. Methods associated with preparation and use of such NEK7 inhibitors, pharmaceutical compositions comprising such NEK7 inhibitors and methods to prevent diseases or disorders (e.g., via modulation of NLRP3 inflammasome activity) are also provided.

Abstract: Compounds having activity as inhibitors of NEK7 are provided. The compounds have structure (I): or a pharmaceutically acceptable salt, stereoisomer or prodrug thereof, wherein A, X, Y, R1, R2, R3 and R4 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 the NLRP3 inflammasome are also provided.

Abstract: Compounds having activity as inhibitors of LRRK2 kinase are provided. The compounds have Structure (I): or a pharmaceutically acceptable salt, stereoisomer or prodrug thereof, wherein A, B, R1a, R1b, R2, 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.

Abstract: Compounds having activity as inhibitors of LRRK2 kinase are provided. The compounds have Structure (I): or a pharmaceutically acceptable salt, stereoisomer or prodrug thereof, wherein A, B, R1a, R1b, R2, 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.

Abstract: Compounds having activity as inhibitors of LRRK2 kinase are provided. The compounds have Structure (I): or a pharmaceutically acceptable salt, stereoisomer or prodrug thereof, wherein A, B, R1a, R1b, R2 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.

Abstract: Compounds having activity as inhibitors of NEK7 are provided. The compounds have Structure (I): or a pharmaceutically acceptable salt, stereoisomer or prodrug thereof, wherein, A, X, Y, R1, R2, R3, R4 and R5 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 the NLRP3 inflammasome are also provided.

Abstract: Compounds having activity as inhibitors of NEK7 are provided. The compounds have Structure (I): or a pharmaceutically acceptable salt, stereoisomer or prodrug thereof, wherein, A, X, Y, R1, R2, R3, R4 and R5 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 the NLRP3 inflammasome are also provided.

Abstract: Compounds having activity as inhibitors of NEK7 are provided. The compounds have Structure (I): or a pharmaceutically acceptable salt, stereoisomer or prodrug thereof, wherein, A, X, Y, R1, R2, R3, R4 and R5 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 the NLRP3 inflammasome are also provided.