## Endpoint to Predict
- Endpoint scope: assay
- Measurement type: IC50
- Label type: continuous
- Binary semantics: pchembl
- Assay description: in vitro kinase inhibition assay: Inhibitory activity can be determined routinely using known methods and also from commercial vendors offering this service for kinases and bromodomain proteins. For example, in vitro kinase inhibition (e.g., PI3K inhibition) can be detected by a standard kinase inhibition assay using labeled ATP to determine if a test compound inhibits the transfer of phosphate from ATP to the kinase substrate. In vivo, PI3K inhibition can be determined from target tissue biopsies by standard tissue processing to disrupt cells and then performing Western Blot analysis to determine the presence or absence of pAKT (substrate of PI3K) relative to a control sample. The activity of a compound of the invention as an inhibitor of a bromodomain-containing protein, such as a BET protein, such as BRD2, BRD3, BRD4, and/or BRDT, or an isoform or mutant thereof, may be determined in vitro, in vivo, or in a cell line. In vitro assays include assays that determine inhibition of bromodomain-containing proteins. Alternatively, inhibitor binding may be determined by running a competition experiment where a provided compound is incubated with a bromodomain-containing protein, such as a BET protein bound to known ligands, labeled or unlabeled. For example, bromodomain inhibition can be determined in vitro using Alpha Screen Technology (http://www.reactionbiology.com/webapps/site/NewsPDFs/Bromodomain%20Assay%20Platform%20for%20Drug%20Screening%20and%20Discovery.pdf). In vivo bromodomain inhibition can be determined indirectly by evaluating the amount of protein present of proteins whose genes' transcription is influenced or controlled by the bromodomain protein, for example, the MYCN protein transcription is controlled by BRD4 (J. E. Delmore et al., Cell 2011, 146, 904-917; A. Puissant, Cancer Discov. 2013, 3, 308-323). Bromodomain inhibition may also be predicted by in silico modeling as described below in the Examples.
- Assay organism: Homo sapiens
- Target name: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform
- Target type: SINGLE PROTEIN
- Target organism: Homo sapiens

## Reference Molecule A
- Canonical SMILES: COC(=O)c1ccc(-c2csc3c(=O)cc(N4CCOCC4)oc23)cc1
- Properties:
- ChEMBL ID: CHEMBL2326953
- Molecule type: Small molecule
- Molecular weight: 371.41
- Heavy atoms: 26
- Hydrogen bond donors: 0
- Hydrogen bond acceptors: 7
- TPSA: 68.98
- LogP: 3.14
- Rotatable bonds: 3
- Ring count: 4
- Aromatic rings: 3
- Formal charge: 0
- Fraction Csp3: 0.26
- QED: 0.66

## Known Reference Result on This Endpoint
- Molecule A clean result: median pChEMBL = 7.92
- This result is provided as context for predicting Molecule B on the same endpoint.

## Reference Molecule A Other ChEMBL Evidence
- type IC50; relation =; value 12; units nM; pChEMBL 7.92; comment 791511

## Query Molecule B
- Canonical SMILES: O=C(NO)c1ccc(-c2csc3c(=O)cc(N4CCOCC4)oc23)cc1
- Properties:
- ChEMBL ID: CHEMBL5874820
- Molecular weight: 372.4
- Heavy atoms: 26
- Hydrogen bond donors: 2
- Hydrogen bond acceptors: 7
- TPSA: 92.01
- LogP: 2.48
- Rotatable bonds: 3
- Ring count: 4
- Aromatic rings: 3
- Formal charge: 0
- Fraction Csp3: 0.22
- QED: 0.54

## Molecule Similarity
- Weighted Tanimoto: 0.76

Answer: 7.28