2. Academic Validation
  3. Discovery and Optimization of wt-RET/KDR-Selective Inhibitors of RETV804M Kinase

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

  • ACS Med Chem Lett. 2020 Feb 28;11(4):497-505. doi: 10.1021/acsmedchemlett.9b00615.
Rebecca Newton 1,  Bohdan Waszkowycz 1,  Chitra Seewooruthun 2,  Daniel Burschowsky 2,  Mark Richards 3,  Samantha Hitchin 1,  Habiba Begum 1,  Amanda Watson 1,  Eleanor French 1,  Niall Hamilton 1,  Stuart Jones 1,  Li-Ying Lin 4,  Ian Waddell 1,  Aude Echalier 2,  Richard Bayliss 3,  Allan M Jordan 1,  Donald Ogilvie 1
Affiliations

Affiliations

  • 1 Drug Discovery Unit, Cancer Research UK, Manchester Institute, University of Manchester, Alderley Park, Macclesfield SK10 4TG, U.K.
  • 2 Department of Molecular and Cell Biology, Henry Wellcome Building, University of Leicester, Lancaster Road, Leicester LE1 7RH, U.K.
  • 3 Astbury Centre for Structural Molecular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, U.K.
  • 4 Leicester Drug Discovery & Diagnostics Centre (LD3), R407a, Hodgkin Building, Lancaster Road, Leicester LE1 7HB, U.K.
PMID: 32292556 DOI: 10.1021/acsmedchemlett.9b00615
Abstract

A combination of focused library and virtual screening, hit expansion, and rational design has resulted in the development of a series of inhibitors of RETV804M kinase, the anticipated drug-resistant mutant of RET kinase. These agents do not inhibit the wild type (wt) isoforms of RET or VEGFR2/KDR/Flk-1 and therefore offer a potential adjunct to RET inhibitors currently undergoing clinical evaluation.

Figures
Products