2. Academic Validation
  3. Discovery, Development, and SAR of Aminothiazoles as LIMK Inhibitors with Cellular Anti-Invasive Properties

Discovery, Development, and SAR of Aminothiazoles as LIMK Inhibitors with Cellular Anti-Invasive Properties

  • J Med Chem. 2015 Oct 22;58(20):8309-13. doi: 10.1021/acs.jmedchem.5b01242.
Mark D Charles 1,  Joanna L Brookfield 1,  Tennyson C Ekwuru 1,  Martin Stockley 1,  John Dunn 1,  Michelle Riddick 1,  Tim Hammonds 2,  Elisabeth Trivier 2,  Gavin Greenland 2,  Ai Ching Wong 2,  Anne Cheasty 1,  Susan Boyd 3,  Diane Crighton 4,  Michael F Olson 4
Affiliations

Affiliations

  • 1 Cancer Research Technology Discovery Laboratories , Jonas Webb Building, Babraham Research Campus, Cambridge CB22 3AT, U.K.
  • 2 Cancer Research Technology Discovery Laboratories, London Bioscience Innovation Centre , Royal College Street, London NW1 0NH, U.K.
  • 3 CompChem Solutions Ltd, St John's Innovation Centre , Cambridge CB4 0WS, U.K.
  • 4 Beatson Institute, Cancer Research U.K. , Garscube Estate, Switchback Road, Glasgow G61 1BD, U.K.
PMID: 26356364 DOI: 10.1021/acs.jmedchem.5b01242
Abstract

As part of a program to develop a small molecule inhibitor of LIMK, a series of aminothiazole inhibitors were discovered by high throughput screening. Scaffold hopping and subsequent SAR directed development led to a series of low nanomolar inhibitors of LIMK1 and LIMK2 that also inhibited the direct biomarker p-cofilin in cells and inhibited the invasion of MDA MB-231-luc cells in a matrigel inverse invasion assay.

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