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Br J Cancer. 2013 Feb 5;108(2):342-50. doi: 10.1038/bjc.2012.576. Epub 2013 Jan 15.

A novel small molecule hydroxamate preferentially inhibits HDAC6 activity and tumour growth.

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Comprehensive Cancer Imaging Centre, Department of Surgery and Cancer Faculty of Medicine, Imperial College London, Hammersmith Hospital, Room 240, MRC Cyclotron Building, Du Cane Road, London W12 0NN, UK.



This study investigates whether a histone deacetylase subtype 6 (HDAC6) inhibitor could be used in the treatment of solid tumours.


We evaluated the effect of a novel inhibitor, C1A, on HDAC6 biochemical activity and cell growth. We further examined potential of early noninvasive imaging of cell proliferation by [(18)F]fluorothymidine positron emission tomography ([(18)F]FLT-PET) to detect therapy response.


C1A induced sustained acetylation of HDAC6 substrates, α-tubulin and HSP90, compared with current clinically approved HDAC inhibitor SAHA. C1A induced apoptosis and inhibited proliferation of a panel of human tumour cell lines from different origins in the low micromolar range. Systemic administration of the drug inhibited the growth of colon tumours in vivo by 78%. The drug showed restricted activity on gene expression with <0.065% of genes modulated during 24 h of treatment. C1A treatment reduced tumour [(18)F]FLT uptake by 1.7-fold at 48 h, suggesting that molecular imaging could provide value in future studies of this compound.


C1A preferentially inhibits HDAC6 and modulates HDAC6 downstream targets leading to growth inhibition of a diverse set of cancer cell lines. This property together with the favourable pharmacokinetics and efficacy in vivo makes it a candidate for further pre-clinical and clinical development.

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