1 / 9

BACKUP SLIDES

BACKUP SLIDES. Strictly confidential. MTT assay shows catalase overexpression has no effects on quinol activity but does significantly reduce H2O2 effects. Catalase overexpression protects from H2O2 but not PMX 290. *. *. * = p < 0.05, Student’s t-test. Strictly confidential.

berit
Download Presentation

BACKUP SLIDES

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. BACKUP SLIDES Strictly confidential

  2. MTT assay shows catalase overexpression has no effects on quinol activity but does significantly reduce H2O2 effects Catalase overexpression protects from H2O2 but not PMX 290 * * * = p < 0.05, Student’s t-test Strictly confidential

  3. PMX 290 is a mammalian thioredoxin reductase (TrxR) inhibitor PMX 290 has been shown to be an irreversible inhibitor of NADPH-reduced mammalian thioredoxin reductase (DTNB assay). IC50 = 2.7 mM Chew et al: FASEB Journal (2008): 22(6), 2072-83. Strictly confidential

  4. PMX 290 (mM) DMSO Time (min) 60 3 15 30 60 HRP- Streptavidin -ratTrxR PMX 290 targets selenium residue of TrxR IC50 (mM) 7.9 8.3 > 75 > 75 > 75 PMX 290 does not inhibit E. coli TrxR/Trx system or yeast glutathione reductase (GR). PMX 290 prevents binding of BIAM that targets selenocysteine residue Chew et al: FASEB Journal (2008): 22(6), 2072-83. Strictly confidential

  5. JNK and p38 inhibitors do not decrease cell death induced by PMX 290 Strictly confidential

  6. VEGF secretion inhibited at sub-toxic concentrations of PMX 290. PMX 290 inhibits VEGF secretion under hypoxic and normoxic conditions Jones et al; Clin. Cancer Research (2006): 12 (18), 5384 – 5394. Strictly confidential

  7. PMX 290 inhibits Hif-1 - HRE DNA binding and decreases mRNA level of Hif target genes Jones et al; Clin. Cancer Research (2006): 12 (18), 5384 – 5394. Strictly confidential

  8. RCC4 - EV RCC4 - VHL PMX 290 increase Hif protein levels in RCC4 cells independently of VHL activity RCC4 have mutant pVHL and so have constitutive Hif expression Expression of wt VHL did not prevent PMX 290 induced Hif expression Jones et al; Clin. Cancer Research (2006): 12 (18), 5384 – 5394. Strictly confidential

  9. PMX 290 increase Hif protein levels in cytoplasm of MDA 468 cells Cytoplasmic Hif levels increase. Nuclear levels remain unchanged. Jones et al; Clin. Cancer Research (2006): 12 (18), 5384 – 5394. Strictly confidential

More Related