Discovery and Optimization of wt-RET/KDR-Selective
Inhibitors of RETV804M Kinase

Newton, Rebecca; Waszkowycz, Bohdan; Seewooruthun, Chitra; Burschowsky, Daniel; Richards, Mark; Hitchin, Samantha; Begum, Habiba; Watson, Amanda; French, Eleanor; Hamilton, Niall; Jones, Stuart; Lin, Li-Ying; Waddell, Ian; Echalier, Aude; Bayliss, Richard; Jordan, Allan M.; Ogilvie, Donald

doi:10.1021/acsmedchemlett.9b00615.s001

ml9b00615_si_001.pdf (515.46 kB)

Discovery and Optimization of wt-RET/KDR-Selective Inhibitors of RET^V804M Kinase

journal contribution

posted on 2020-03-05, 20:08 authored by Rebecca Newton, Bohdan Waszkowycz, Chitra Seewooruthun, Daniel Burschowsky, Mark Richards, Samantha Hitchin, Habiba Begum, Amanda Watson, Eleanor French, Niall Hamilton, Stuart Jones, Li-Ying Lin, Ian Waddell, Aude Echalier, Richard Bayliss, Allan M. Jordan, Donald Ogilvie

A combination of focused library and virtual screening, hit expansion, and rational design has resulted in the development of a series of inhibitors of RET^V804M kinase, the anticipated drug-resistant mutant of RET kinase. These agents do not inhibit the wild type (wt) isoforms of RET or KDR and therefore offer a potential adjunct to RET inhibitors currently undergoing clinical evaluation.