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MDA-MB-468 48h MDA-MB-231 48h a MDA-MB-231 72h MDA-MB-468 MDA-MB-436 48h MDA-MB-436 72h MCF-7 48h MCF-7 72h b c ef g h MDA-MB-468 72h clomipramine.

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Presentation on theme: "MDA-MB-468 48h MDA-MB-231 48h a MDA-MB-231 72h MDA-MB-468 MDA-MB-436 48h MDA-MB-436 72h MCF-7 48h MCF-7 72h b c ef g h MDA-MB-468 72h clomipramine."— Presentation transcript:

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4 MDA-MB-468 48h MDA-MB-231 48h a MDA-MB-231 72h MDA-MB-468 MDA-MB-436 48h MDA-MB-436 72h MCF-7 48h MCF-7 72h b c ef g h MDA-MB-468 72h clomipramine norclomipramine d Supplementary Figure S4 norclomipramine clomipramine norclomipramine clomipramine norclomipramine clomipramine norclomipramine clomipramine norclomipramine clomipramine norclomipramine clomipramine norclomipramine clomipramine concentration (  M ) Rossi et al. “HECT E3 ligase ITCH inhibitors”

5 a c e d b f Supplementary Figure S5 norclomipramine clomipramine norclomipramine clomipramine norclomipramine clomipramine norclomipramine clomipramine norclomipramine clomipramine norclomipramine clomipramine PC3 72hPC3 48h DU145 72hDU145 48h LNCaP 72hLNCaP 48h Rossi et al. “HECT E3 ligase ITCH inhibitors”

6 T24 72h RT112 72h MCR HT-1376 48h MCR 72h b cd e gh Supplementary Figure S6 MCR 48h norclomipramine clomipramine norclomipramine clomipramine norclomipramine clomipramine norclomipramine clomipramine norclomipramine clomipramine norclomipramine clomipramine f HT-1376 72h norclomipramine clomipramine a T24 48h Rossi et al. “HECT E3 ligase ITCH inhibitors” norclomipramine clomipramine RT112 48h

7 Supplementary Table 1 Rossi et al. “HECT E3 ligase ITCH inhibitors” DrugCI 50 1 DRI50 2 Interpretation norclomipramine 72h/MIT 48h (50:50) 0,0738norclomipramine:18MIT:54 Strong synergirm clomipramine 72h/Gem 48h (50:50) 0,1372clomipramine:11GEM:23 Strong synergirm 1 CI50 were calculated for 50% cell survival (ED50) by isobologram analyses performed with CalcuSyn software. 2 DRI represents the order of magnitude (fold) of dose reduction obtained for ED50 effect in combination setting as compared to each drug alone.

8 IC 50 values (µM) of clomipramine or norclomipramine in human breast cancer cell lines a Supplementary Table 2 a Data are shown as mean±SD. MDA 231MDA 468MDA 436MCF-7 norclomipramine 48h IC 50 7.86 ± 0.027.27 ± 0.076.22 ± 0.0410.33 ± 0.02 72h6.72 ± 0.035.98 ± 0.027.27 ± 0.0210.73 ± 0.02 clomipramine 48h IC 50 18.53 ± 0.0212.55 ± 0.0220.85 ± 0.0622.51 ± 0.02 72h14.10 ± 0.029.18 ± 0.0215.25 ± 0.0113.06 ± 0.01 Rossi et al. “HECT E3 ligase ITCH inhibitors”

9 PC3DU145LNCaP norclomipramine 48h IC 50 14.10 ± 0.048.49 ± 0.0212.55 ± 0.02 72h11.29 ± 0.037.07 ± 0.0510.45 ± 0.04 clomipramine 48h IC 50 29.58 ± 0.0120.85 ± 0.0430.77 ± 0.04 72h26.38 ± 0.0412.94 ± 0.0231.41 ± 0.01 Supplementary Table 3 IC 50 values (µM) of clomipramine or norclomipramine in human prostate cancer cell lines a a Data are shown as mean±SD. Rossi et al. “HECT E3 ligase ITCH inhibitors”

10 T24RT112HT-1376MCR norclomipramine 48h IC 50 7.86 ± 0.0313.55 ± 0.0115.25 ± 0.0213.55 ± 0.01 72h6.72 ± 0.0510.73 ± 0.0513.06 ± 0.0513.55 ± 0.02 clomipramine 48h IC 50 29.58 ± 0.0124.35 ± 0.01 34.55 ± 0.14 28.44 ± 0.04 72h24.35 ± 0.0914.66 ± 0.0329.58 ± 0.0333.28 ± 0.03 Supplementary Table 4 IC 50 values (µM) of clomipramine or norclomipramine in human bladder cancer cell lines a a Data are shown as mean±SD. Rossi et al. “HECT E3 ligase ITCH inhibitors”

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