Geographical distribution of stem cell transplants in France in patients newly diagnosed with myeloma in 2012.

<p>Fig 2A. Geographical distribution of stem cell transplants performed in patients less than 65 years old at diagnosis during their follow-up. Stem cell transplants were performed in 39 administrative areas or “Départements”. Fig 2B. Probability of proceeding to a stem cell transplant according to place of residence in patients less than 65 years old and having received therapy in the hospital for their disease.</p

Associated diagnoses of neoplasia in patients diagnosed with myeloma in 2012.

<p>Associated diagnoses of neoplasia in patients diagnosed with myeloma in 2012.</p

Ranking of the selected hits using the MM-PBSA method compared to that of AutoDock.

<p>Ranking of the selected hits using the MM-PBSA method compared to that of AutoDock.</p

ERCC1-XPA interactions.

<p>The binding between ERCC1 (teal) and XPA (red) is primarily mediated by 5 residues from XPA peptide, namely; G72, G73, G74, F75 and I76. On the other hand, the contribution from the ERCC1 binding site is distributed among 10 residues; R106, Q107, G109, N110, P111, F140, L141, S142, Y145 and Y152.</p

Fluorescence quenching intensity profiles of ERCC1^92–214 (20 µM, red line) in the presence of caffeine (0 µM dash line, 40 µM, 80 µM and 320 µM black line) in HBS-EP buffer (0.01 M HEPES pH 7.4, 0.15 M NaCl, 3 mM EDTA, 0.005% surfactant P20).

<p>λexcit-295 nm, slit width 4 nm.</p

Structures of the 14 experimentally tested compounds.

<p>NERI01 is compound 12.</p

Inhibitory concentrations 50 (IC₅₀) and CI95 for cisplatin and compound 12 in HCT116 and A549 cells.

<p>Results are mean values from three independent experiments ± standard error of means. Synergy is defined as CI₉₅<0.9, additivity for 0.9< CI₉₅<1.1 and antagonism as CI₉₅>1.1.</p

Selection of an initial ERCC1 target.

<p>The root mean square deviation (RMSD) of 9 ERCC1 NMR structures relative to an arbitrary NMR conformation. The centroid of the 9 structures (highlighted in red) was selected as the initial target structure against the full set of compounds included in the CN library.</p

Fluorescence intensity profiles (A and C) and the corresponding plots of 1/ΔFI versus [L] (B and D) for ERCC1^92–214 in presence of compounds 12 (A and B) and 10 (C and D).

<p>Fluorescence intensity profiles were obtained by monitoring the Tryptophan quenching of ERCC192-214 (20 µM) in the presence of ligand 12 (a-0 µM, b-10 µM, c-20 µM, d-40 µM, e-60 µM, f-80 µM, g-160, h-320 µM) and 10 (a-0 µM, b-5 µM, c-10 µM, d-20 µM, e-40 µM, f-60 µM) at the excitation wavelenght of 295 nm. In red, fluorescence intensity profile for ERCC1^92–214 alone.</p

Percentage of protein homology obtained from UniProt Web Site (http://www.uniprot.org/) by blasting human cytosolic 5’-nucleotidase II primary sequence (P49902) with others belong to different vertebrates: <i>Pongo abelii</i> (Q5RA22), <i>Bos Taurus</i> (B1H0W4), <i>Mus musculus</i> (E9Q9M1), <i>Myotis brandtii</i> (S7PW19), <i>Gallus gallus</i> (F1NCR3), <i>Chelonia mydas</i> (M7BZT7), <i>Xenopus laevis</i> (Q6DKB0) and <i>Dario rerio</i> (F1QAK5).

<p>Percentage of protein homology obtained from UniProt Web Site (<a href="http://www.uniprot.org/" target="_blank">http://www.uniprot.org/</a>) by blasting human cytosolic 5’-nucleotidase II primary sequence (P49902) with others belong to different vertebrates: <i>Pongo abelii</i> (Q5RA22), <i>Bos Taurus</i> (B1H0W4), <i>Mus musculus</i> (E9Q9M1), <i>Myotis brandtii</i> (S7PW19), <i>Gallus gallus</i> (F1NCR3), <i>Chelonia mydas</i> (M7BZT7), <i>Xenopus laevis</i> (Q6DKB0) and <i>Dario rerio</i> (F1QAK5).</p