Caroline Richardson

TL;DR: KU-55933 is a novel, specific, and potent inhibitor of the ATM kinase, which did not potentiate the cytotoxic effects of ionizing radiation on ataxia-telangiectasia cells, nor did it affect their cell cycle profile after DNA damage.

TL;DR: NU7441 shows sufficient proof of principle through in vitro and in vivo chemos Sensitization and radiosensitization to justify further development of DNA-PK inhibitors for clinical use.

TL;DR: A solution-phase multiple-parallel synthesis approach was employed for the preparation of 6, 7- and 8-aryl-substituted chromenone libraries, which were screened as inhibitors of the DNA repair enzyme DNA-dependent protein kinase (DNA-PK) and resulted in the identification of 8-dibenzothiophen-4-yl-2-morpholin-4,yl-chromen-4 one as a highly potent and selective DNA-PK inhibitor.

TL;DR: There was a correlation between the ability of the inhibitors to prevent IR-induced DNA DSB repair and their ability to potentiate cytotoxicity and the DNA-PK and PARP-1 inhibitors show potential as tools for anticancer therapeutic intervention.

TL;DR: This work resulted in a promising lead compound which exhibits tight and selective binding to KEAP1, and activates the NRF2 antioxidant response in cellular and in vivo models, thereby providing a high quality chemical probe to explore the therapeutic potential of disrupting theKEAP1-NRF2 interaction.