ars.els-cdn.com · web view– overview of atr (pdb id 2idx) showing the location of the atp...

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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