Dana-farber-cancer Institute Inc.

Behnam Nabet

Andrew John Phillips

Dennis Buckley

Georg Winter

Timothy P Heffernan

Justin Roberts

James Elliott Bradner

James Bradner

Nathanael S Gray

David A Scott

Brian Groendyke

Mikaela Mohardt

Andrew J Phillips

Disclosed are compounds that possess inhibitory activity against FAK. Also disclosed are pharmaceutical compositions containing the compounds and methods of using the compounds to treat cancer mediated by aberrant FAK activity.

Small-molecule focal adhesion kinase (FAK) inhibitors

The present invention provides a means to modulate gene expression in vivo in a manner that avoids problems associated with CRISPR endogenous protein knock-out or knock-in strategies and strategies that provide for correction, or alteration, of single nucleotides. The invention includes inserting into the genome a nucleotide encoding a heterobifunctional compound targeting protein (dTAG) in-frame with the nucleotide sequence of a gene encoding an endogenously expressed protein of interest which, upon expression, produces an endogenous protein-dTAG hybrid protein. This allows for targeted protein degradation of the dTAG and the fused endogenous protein using a heterobifunctional compound.

Tunable endogenous protein degradation with heterobifunctional compounds

This invention is in the area of compositions and methods for regulating chimeric antigen receptor immune effector cell, for example T-cell (CAR-T), therapy to modulate associated adverse inflammatory responses, for example, cytokine release syndrome and tumor lysis syndrome, using targeted protein degradation.

Regulating chimeric antigen receptors

Tunable endogenous protein degradation

Targeted protein degradation to attenuate adoptive T-cell therapy associated adverse inflammatory responses

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Behnam Nabet