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Antitumour Quinols as Novel Inhibitors of Thioredoxin Signalling

◆ 10% Tween/PBS ▲ 200 mg/kg i.p. d 8 ■ 50 mg/kg i.p.d 8-12. Proposed quinol-thioredoxin binding geometry. Cell cycle perturbation by Quinols. NCI mean LC 50 graphs: AW 464 BW 114. Con. 24 h. G1/0. S. G2/M. } Colon. Cell Number. Inhibition of Tx/TR signalling:

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Antitumour Quinols as Novel Inhibitors of Thioredoxin Signalling

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  1. ◆ 10% Tween/PBS ▲ 200 mg/kg i.p. d 8 ■ 50 mg/kg i.p.d 8-12 Proposed quinol-thioredoxin binding geometry Cell cycle perturbation by Quinols NCI mean LC50 graphs: AW 464 BW 114 Con 24 h G1/0 S G2/M }Colon Cell Number Inhibition of Tx/TR signalling: Effect of incubation ot Tx/TR with quinol prior to addition of insulin 48 h 72 h NCI Propidium Iodide Staining HCT116 colon carcinoma cells treated 0.5μM BW 114 }Renal Effects of Quinols on the expression of CDK1 in HCT116 cells following 48h treatment BW 114 AW 464 C 0.1 0.25 0.5 μM CDK 1 Effect of BW 114 on growth of MDA-MB-435 xenografts. Reference: Wells, G., Berry, J.M., Bradshaw, T.D., Burger, A.M., Seaton, A., Wang, B., Westwell, A.D. and Stevens, M.F.G. J.Med.Chem. 2003, 46, 532-541 Acknowledgements: Carl Schwalbe (Aston, U.K.), Iduna Fichtner (Berlin, Germany), NCI Developmental Therapeutics, EORTC SPG Group Antitumour Quinols as Novel Inhibitors of Thioredoxin Signalling Jane M. Berry, Andrew D. Westwell, Charles A. Laughton, Charles S. Matthews, Malcolm F.G. Stevens and Tracey D. Bradshaw School of Pharmaceutical Sciences, University of Nottingham, Nottingham, NG7 2RD, UK. Induction of Thioredoxin Reductase mRNA in HCT 116 cells treated with 1 μM AW 464

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