title: Discovery, Development, and SAR of Aminothiazoles as LIMK Inhibitors with Cellular Anti-Invasive Properties.
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.
authors.affiliation: Cancer Research Technology Discovery Laboratories , Jonas Webb Building, Babraham Research Campus, Cambridge CB22 3AT, U.K.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Charles
authors.affiliation: Cancer Research Technology Discovery Laboratories , Jonas Webb Building, Babraham Research Campus, Cambridge CB22 3AT, U.K.
authors.forename: Joanna L
authors.initials: JL
authors.lastname: Brookfield
authors.affiliation: Cancer Research Technology Discovery Laboratories , Jonas Webb Building, Babraham Research Campus, Cambridge CB22 3AT, U.K.
authors.forename: Tennyson C
authors.initials: TC
authors.lastname: Ekwuru
authors.affiliation: Cancer Research Technology Discovery Laboratories , Jonas Webb Building, Babraham Research Campus, Cambridge CB22 3AT, U.K.
authors.forename: Martin
authors.initials: M
authors.lastname: Stockley
authors.affiliation: Cancer Research Technology Discovery Laboratories , Jonas Webb Building, Babraham Research Campus, Cambridge CB22 3AT, U.K.
authors.forename: John
authors.initials: J
authors.lastname: Dunn
authors.affiliation: Cancer Research Technology Discovery Laboratories , Jonas Webb Building, Babraham Research Campus, Cambridge CB22 3AT, U.K.
authors.forename: Michelle
authors.initials: M
authors.lastname: Riddick
authors.affiliation: Cancer Research Technology Discovery Laboratories, London Bioscience Innovation Centre , Royal College Street, London NW1 0NH, U.K.
authors.forename: Tim
authors.initials: T
authors.lastname: Hammonds
authors.affiliation: Cancer Research Technology Discovery Laboratories, London Bioscience Innovation Centre , Royal College Street, London NW1 0NH, U.K.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Trivier
authors.affiliation: Cancer Research Technology Discovery Laboratories, London Bioscience Innovation Centre , Royal College Street, London NW1 0NH, U.K.
authors.forename: Gavin
authors.initials: G
authors.lastname: Greenland
authors.affiliation: Cancer Research Technology Discovery Laboratories, London Bioscience Innovation Centre , Royal College Street, London NW1 0NH, U.K.
authors.forename: Ai Ching
authors.initials: AC
authors.lastname: Wong
authors.affiliation: Cancer Research Technology Discovery Laboratories , Jonas Webb Building, Babraham Research Campus, Cambridge CB22 3AT, U.K.
authors.forename: Anne
authors.initials: A
authors.lastname: Cheasty
authors.affiliation: CompChem Solutions Ltd, St John's Innovation Centre , Cambridge CB4 0WS, U.K.
authors.forename: Susan
authors.initials: S
authors.lastname: Boyd
authors.affiliation: Beatson Institute, Cancer Research U.K. , Garscube Estate, Switchback Road, Glasgow G61 1BD, U.K.
authors.forename: Diane
authors.initials: D
authors.lastname: Crighton
authors.affiliation: Beatson Institute, Cancer Research U.K. , Garscube Estate, Switchback Road, Glasgow G61 1BD, U.K.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Olson
mesh_terms: D051339:Actin Depolymerizing Factors / Q000378:metabolism; D000818:Animals; D001711:Biotransformation; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D057166:High-Throughput Screening Assays; D006801:Humans; D054461:Lim Kinases / Q000037:antagonists & inhibitors*; D008862:Microsomes, Liver / Q000378:metabolism; D009361:Neoplasm Invasiveness; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D051339:Actin Depolymerizing Factors; D004791:Enzyme Inhibitors; D013844:Thiazoles; C515892:LIMK1 protein, human; C102895:LIMK2 protein, human; D054461:Lim Kinases