Dana-farber-cancer Institute Inc.

Calla M Olson

Nathanael Schiander Gray

Tinghu Zhang

Yanke Liang

Nicholas Paul Kwiatkowski

Nathanael S Gray

David A Scott

Eric S Fischer

Radoslaw Nowak

Katherine Donovan

Baishan Jiang

Eric Wang

Zhengnian Li

Benika J Pinch

Disclosed are bifunctional compounds (degraders) that target Wee1 tyrosine kinase for degradation. Also disclosed are pharmaceutical compositions containing the degraders and methods of using the compounds to treat disease.

Degraders of WEE1 kinase

The present application provides bifunctional compounds of Formula (Ia) or (Ib): or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, which act as protein degradation inducing moieties for cyclin-dependent kinase 8 (CDK8). The present application also relates to methods for the targeted degradation of CDK8 through the use of the bifunctional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to CDK8 which can be utilized in the treatment of disorders modulated by CDK8.

Degradation of cyclin-dependent kinase 8 (CDK8) by conjugation of CDK8 inhibitors with E3 ligase ligand and methods of use

The present application provides bifunctional compounds of Formula (I): or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, which act as protein degradation inducing moieties for cyclin-dependent kinase 4 (CDK4) and/or cyclin-dependent kinase 6 (CDK6). The present application also relates to methods for the targeted degradation of CDK4 and/or CDK6 through the use of the bifunctional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to CDK4 and/or CDK6 which can be utilized in the treatment of disorders modulated by CDK4 and/or CDK6.

Degradation of cyclin-dependent kinase 4/6 (CDK4/6) by conjugation of CDK4/6 inhibitors with E3 ligase ligand and methods of use

The present application provides bifunctional compounds of Formula (I): or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, which act as protein degradation inducing moieties for cyclin-dependent kinase 9 (CDK9), the present application also relates to methods for the targeted degradation of CDK9 through the use of the bifunctional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to CDK9 which can be utilized in the treatment of disorders modulated by CDK9.

Degradation of cyclin-dependent kinase 9 (CDK9) by conjugation of CDK9 inhibitors with E3 ligase ligand and methods of use

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Brookline, MA, United States of America

Calla M Olson