Abstract: Compounds and methods for modulating RAS-PI3K.

Abstract: Disclosed are compounds of Formula (I): or pharmaceutically acceptable salts or solvates thereof, wherein R1, R3, X, Y, Z, and W are as defined herein. The compounds are, for example, inhibitors of WRN helicase and useful in treating a proliferative disease, such as cancer.

Abstract: Disclosed herein are compounds selective for JAK1, pharmaceutical compositions comprising said compounds, and methods of using said compounds.

Abstract: Disclosed are compounds of Formula (I): or pharmaceutically acceptable salts or solvates thereof, wherein R1, R3, X, Y, Z, and W are as defined herein. The compounds are, for example, inhibitors of WRN helicase and useful in treating a proliferative disease, such as cancer.

Abstract: Disclosed are compounds of Formula (I): or pharmaceutically acceptable salts or solvates thereof, wherein R1, R3, X, Y, Z, and W are as defined herein. The compounds are, for example, inhibitors of WRN helicase and useful in treating a proliferative disease, such as cancer.

Abstract: Disclosed herein are compositions and methods for modulating cereblon neosubstrates. A small molecule modulator of Formula (I*), or a pharmaceutically acceptable salt or solvate thereof can be used to modulate cereblon neosubstrates.

Abstract: Disclosed herein are in vivo engineered cereblon protein and methods of making the same. The in vivo engineered cereblon protein can include a site-specific non-naturally occurring modification at cysteine 287 as set forth in SEQ ID NO:1, or cysteine 286 as set forth in SEQ ID NO: 2 or 3, the modification comprising a moiety resulting from an in vivo Michael addition reaction between an exogenous Michael acceptor and the cysteine 287 as set forth in SEQ ID NO: 1, or cysteine 286 as set forth in SEQ ID NO: 2 or 3.

Abstract: Disclosed herein are compositions and methods for modulating cereblon neosubstrates. A small molecule modulator of Formula (I*), or a pharmaceutically acceptable salt or solvate thereof can be used to modulate cereblon neosubstrates.

Abstract: Disclosed herein are in vivo engineered cereblon protein and methods of making the same. The in vivo engineered cereblon protein can include a site-specific non-naturally occurring modification at cysteine 287 as set forth in SEQ ID NO:1, or cysteine 286 as set forth in SEQ ID NO: 2 or 3, the modification comprising a moiety resulting from an in vivo Michael addition reaction between an exogenous Michael acceptor and the cysteine 287 as set forth in SEQ ID NO:1, or cysteine 286 as set forth in SEQ ID NO: 2 or 3.

Abstract: Disclosed herein are compositions and methods for modulating cereblon neosubstrates. A small molecule modulator of Formula (I*), or a pharmaceutically acceptable salt or solvate thereof can be used to modulate cereblon neosubstrates.

Abstract: Disclosed herein are in vivo engineered cereblon protein and methods of making the same. The in vivo engineered cereblon protein can include a site-specific non-naturally occurring modification at cysteine 287 as set forth in SEQ ID NO:1, or cysteine 286 as set forth in SEQ ID NO:2 or 3, the modification comprising a moiety resulting from an in vivo Michael addition reaction between an exogenous Michael acceptor and the cysteine 287 as set forth in SEQ ID NO:1, or cysteine 286 as set forth in SEQ ID NO:2 or 3.

Abstract: Disclosed herein are protein-probe adducts and synthetic ligands that inhibit protein-probe adduct formation, in which the protein is part of the E3 ligase complex and the protein is modified to alter the substrate recognition of the E3 ligase complex. In some instances, also provided herein are protein-probe adducts and synthetic ligands that inhibit protein-probe adduct formation, in which the protein is modified or tagged for degradation. In some instances, additionally provided herein are cysteine-containing protein binding domains that interact with a probe and/or a ligand described herein.

Abstract: Disclosed herein are in vivo engineered cereblon protein and methods of making the same. The in vivo engineered cereblon protein can include a site-specific non-naturally occurring modification at cysteine 287 as set forth in SEQ ID NO:1, or cysteine 286 as set forth in SEQ ID NO: 2 or 3, the modification comprising a moiety resulting from an in vivo Michael addition reaction between an exogenous Michael acceptor and the cysteine 287 as set forth in SEQ ID NO:1, or cysteine 286 as set forth in SEQ ID NO: 2 or 3.

Abstract: Disclosed herein are compositions and methods for modulating cereblon neosubstrates. A small molecule modulator of Formula (I*), or a pharmaceutically acceptable salt or solvate thereof can be used to modulate cereblon neosubstrates.