## Endpoint to Predict
- Endpoint scope: assay
- Measurement type: IC50
- Label type: continuous
- Binary semantics: pchembl
- Assay description: Binding Assay ATR (tracer B): For the assay 50 nl of a 100-fold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384 well microtiter plate (MTP, Greiner Bio-One, Frickenhausen, Germany). To prepare the ATR-working solution, ATR/ATRIP stock solution was diluted in assay buffer [50 mM HEPES (pH 7), 10 mM MgCl2, 1 mM DTT, 0.01% (w/v) Igepal, 0.01% (w/v) BSA] to 4.2 nM protein concentration (concentration may vary from lot to lot of protein preparation). AntiGST-Tb antibody was diluted to 4.2 nM. The ATR-working solution was incubated for 30 min at 22° C. prior to dispensing to pre-form the complex of antiGST-Tb+GST-ATR+ATRIP. Then, 3 μl of the ATR-working solution were added to the test compound and the mixture was incubated for 10 min at 22° C. to allow pre-binding of the test compounds to ATR/ATRIP. Then, 2 μl of a 100 nM solution of either tracer A or B in assay buffer were added to the ATR-working solution. The resulting mixture was incubated for 30 min at 22° C. The measurement of the TR-FRET signal was performed in a standard HTRF-compatible MTP reader instrument (e.g. BMG Pherastar) by recording the fluorescence emissions at 545 nm and 570 nm after excitation at 337-350 nm. The ratio between emission at 570 nm divided by emission at 545 nm was calculated to give the well ratio. The experimental data (well ratios) were normalised by the following way: positive control contained ATR-working solution plus either tracer B solution (3′,6′-bis(dimethylamino)-N-[4-({2-[(3R)-3-methylmorpholin-4-yl]-8-(1H-pyrazol-5-yl)-1,7-naphthyridin-4-yl}oxy)butyl]-3-oxo-3H-spiro[2-benzofuran-1,9′-xanthene]-5-carboxamide =0% inhibition), the negative control contained all components except GST-ATR/ATRIP (=100% inhibition). Usually the compounds were tested on the same MTP in 11 different concentrations in the range of 20 μM to 0.1 nM (20 μM, 5.9 μM, 1.7 μM, 0.51 μM, 0.15 μM, 44 nM, 13 nM, 3.8 nM, 1.1 nM, 0.33 nM and 0.1 nM). The dilution series were prepared separately before the assay on the level of the 100 fold concentrated solutions in DMSO by serial 1:3.4 dilutions in duplicate values for each concentration. IC50 values were calculated by a 4 parameter fit using standard software (GraphPad prism or equivalent).
- Target name: ATR/ATRIP
- Target type: PROTEIN COMPLEX
- Target organism: Homo sapiens

## Reference Molecule A
- Canonical SMILES: CS(=O)(=O)Cc1cc(N2CCOCC2)nc2c(-c3ccn[nH]3)nccc12
- Properties:
- ChEMBL ID: CHEMBL5882996
- Molecular weight: 373.44
- Heavy atoms: 26
- Hydrogen bond donors: 1
- Hydrogen bond acceptors: 7
- TPSA: 101.07
- LogP: 1.4
- Rotatable bonds: 4
- Ring count: 4
- Aromatic rings: 3
- Formal charge: 0
- Fraction Csp3: 0.35
- QED: 0.74

## Known Reference Result on This Endpoint
- Molecule A clean result: median pChEMBL = 6.9
- This result is provided as context for predicting Molecule B on the same endpoint.

## Reference Molecule A Other ChEMBL Evidence
- type IC50; relation =; value 127; units nM; pChEMBL 6.9; comment 1230388

## Query Molecule B
- Canonical SMILES: C[C@@H]1COCCN1c1cc(C2CC2)c2ccnc(-c3cc[nH]n3)c2n1
- Properties:
- ChEMBL ID: CHEMBL5861518
- Molecular weight: 335.41
- Heavy atoms: 25
- Hydrogen bond donors: 1
- Hydrogen bond acceptors: 5
- TPSA: 66.93
- LogP: 3.12
- Rotatable bonds: 3
- Ring count: 5
- Aromatic rings: 3
- Formal charge: 0
- Fraction Csp3: 0.42
- QED: 0.8

## Molecule Similarity
- Weighted Tanimoto: 0.36

Answer: 8.04