Roman Sarott, Sai Gourisankar, Basel Karim, Sabin Nettles, Haopeng Yang, Brendan G Dwyer, Juste M Simanauskaite, Jason Tse, Hind Abuzaid, Andrey Krokhotin, Tinghu Zhang, Stephen M Hinshaw, Michael R Green, Gerald R Crabtree, Nathanael S Gray
Protein kinases are disease drivers whose therapeutic targeting traditionally centers on inhibition of enzymatic activity. Here chemically induced proximity is leveraged to convert kinase inhibitors into context-specific activators of therapeutic genes. Bivalent molecules that link ligands of the transcription factor B-cell lymphoma 6 (BCL6) to ATP-competitive inhibitors of cyclin-dependent kinases (CDKs) were developed to re-localize CDK to BCL6-bound loci on chromatin and direct phosphorylation of RNA Pol II...
October 25, 2023: bioRxiv