ars.els-cdn.com · web view– overview of atr (pdb id 2idx) showing the location of the atp...
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Table S1 – Drug likeness score for compounds V and VI obtained with the Molinspiration Cheminformatics
Software.
MW – Molecular weight
miLogP – Octanol-water partition coefficient logP
TPSA – Topological polar surface area
ON – Hydrogen bond acceptors
OHNH – Hydrogen bond donors
Nº Rotb – Number of rotable bonds
Table S2 – Bioactivity scores for compounds V and VI obtained with the Molinspiration Cheminformatics
Software.
Compound GPCR ligand
Ion channel
modulator
Kinase inhibitor
Nuclear receptor ligand
Protease inhibitor
Enzyme inhibitor
V -0.64 -0.62 -0.65 -1.02 -0.56 -0.50VI -0.14 -0.42 0.37 0.01 -0.64 -0.07
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Compound MW (Da) miLogP TPSA Nº
AtomsNº ON
Nº OHNH
Nº Violations
Nº Rotb
V 269.84 2.91 53.15 21 4 3 0 6VI 245.22 3.33 69.14 21 4 3 0 2
Figure S1 – Overview of ATR (PDB ID 2IDX) showing the location of the ATP residue and the proximity with the cluster of residues R186, R190, R191 and E193 bearing the mutations analyzed
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Figure S2 - Chemical structures of compound V and VI
.
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Figure S3 – Concentration-dependent curves for WT and ATR mutants obtained by differential scanning
fluorimetry in the presence of compound V (dark grey line) or compound VI (light grey line). ΔTm (°C) was
calculated as the difference between the Tm (°C) in the presence of each compound and Tm (°C) obtained in
the presence of DMSO (2%).
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Figure S4 – Effect of the compounds on the viability of an ATR patient derived fibroblasts (c.290 G>A/
c.349-1 G>C). Cells were incubated with different concentrations of the compounds V and VI for 72 h.
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Figure S5 – Effect of the compounds V and VI on the viability of HepaRGTM cells. Cells were incubated
with different concentrations of the two compounds for 72 h.
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