## Endpoint to Predict
- Endpoint scope: assay
- Measurement type: IC50
- Label type: continuous
- Binary semantics: pchembl
- Assay description: Cellular Assay: Assay a) HT29 cells (ECACC #85061109) were seeded into 384 well assay plates (Costar #3712) at a density of 3500 cells/well in 40 μl EMEM medium containing 1% L glutamine and 10% FBS and allowed to adhere overnight. The following morning compounds of Formula (I) in 100% DMSO were added to assay plates by acoustic dispensing. After 1 h incubation at 37° C. and 5% CO2 plates (up to 6 at a time) were irradiated using the X-RAD 320 instrument (PXi) with equivalent to Ë¿600 cGy. Plates were returned to the incubator for a further 1 h. Then cells were fixed by adding 20 μl of 3.7% formaldehyde in PBS solution and incubating for 20 minutes at r.t. before being washed with 50 μl/well PBS, using a Biotek EL405 plate washer. Then 20 μ 0.1% Triton X100 in PBS was added and incubated for 20 minutes at r.t., to permeabalise cells. Then the plates were washed once with 50 μl/well PBS, using a Biotek EL405 plate washer. Phospho-ATM Ser1981 antibody (Millipore #MAB3806) was diluted 10000 fold in PBS containing 0.05% polysorbate/Tween and 3% BSA and 20 μl was added to each well and incubated over night at r.t. The next morning plates were washed three times with 50 μl/well PBS, using a Biotek EL405 plate washer, and then 20 μl of secondary Ab solution, containing 500 fold diluted Alexa Fluor® 488 Goat anti-rabbit IgG (Life Technologies, A11001) and 0 mg/ml Hoeschst dye (Life technologies #H-3570), in PBS containing 0.05% polysorbate/Tween and 3% BSA, was added. After 1 h incubation at r.t., the plates were washed three times with 50 μl/well PBS, using a Biotek EL405 plate washer, and plates were sealed and kept in PBS at 4° C. until read. Plates were read using an ArrayScan VTI instrument, using an XF53 filter with 10× objective. A two laser set up was used to analyse nuclear staining with Hoeschst (405 nm) and secondary antibody staining of pSer1981 (488 nm).
- Assay cell type: HT-29
- Target name: Serine-protein kinase ATM
- Target type: SINGLE PROTEIN
- Target organism: Homo sapiens

## Reference Molecule A
- Canonical SMILES: COC(=O)N1CCC(n2c(=O)n(C)c3cnc4ccc(-c5ccc(OC)nc5)cc4c32)CC1
- Properties:
- ChEMBL ID: CHEMBL3967825
- Molecule type: Small molecule
- Molecular weight: 447.5
- Heavy atoms: 33
- Hydrogen bond donors: 0
- Hydrogen bond acceptors: 6
- TPSA: 91.48
- LogP: 3.36
- Rotatable bonds: 3
- Ring count: 5
- Aromatic rings: 4
- Formal charge: 0
- Fraction Csp3: 0.33
- QED: 0.48

## Known Reference Result on This Endpoint
- Molecule A clean result: median pChEMBL = 7.95
- This result is provided as context for predicting Molecule B on the same endpoint.

## Reference Molecule A Other ChEMBL Evidence
- type IC50; relation =; value 11.2; units nM; pChEMBL 7.95; comment 427953

## Query Molecule B
- Canonical SMILES: CN(C)CCCOc1ccc(-c2ccc3ncc4[nH]c(=O)n(C5CCOCC5)c4c3c2)cn1
- Properties:
- ChEMBL ID: CHEMBL3907190
- Molecule type: Small molecule
- Molecular weight: 447.54
- Heavy atoms: 33
- Hydrogen bond donors: 1
- Hydrogen bond acceptors: 6
- TPSA: 85.27
- LogP: 3.62
- Rotatable bonds: 7
- Ring count: 5
- Aromatic rings: 4
- Formal charge: 0
- Fraction Csp3: 0.4
- QED: 0.44

## Molecule Similarity
- Weighted Tanimoto: 0.42

Answer: 8.49