## Endpoint to Predict
- Endpoint scope: assay
- Measurement type: IC50
- Label type: continuous
- Binary semantics: pchembl
- Assay description: PI3K Enzyme Assay A2: Materials: Lipid kinase substrate, phosphoinositol-4,5-bisphosphate (PIP2), was purchased from Echelon Biosciences (Salt Lake City, Utah). PI3K isoforms α, β, δ and γ were purchased from Millipore (Bedford, Mass.). ATP, MgCh, DTT, EDTA, MOPS and CHAPS were purchased from Sigma-Aldrich (St. Louis, Mo.).The kinase reaction was conducted in clear-bottom 96-well plate from Thermo Fisher Scientific in a final volume of 24 μL. Inhibitors were first diluted serially in DMSO and added to the plate wells before the addition of other reaction components. The final concentration of DMSO in the assay was 0.5%. The PI3K assays were carried out at room temperature in 20 mM MOPS, pH 6.7, 10 mM MgCl2, 5 mM DTT and CHAPS 0.03%. The reaction mixture was prepared containing 50 μM PIP2, kinase and varying concentration of inhibitors. Reactions were initiated by the addition of ATP containing 2.2 μCi [γ-33P]ATP to a final concentration of 1000 μM. The final concentration of PI3K isoforms α, β, δ and γ in the assay were 1.3, 9.4, 2.9 and 10.8 nM respectively. Reactions were incubated for 180 min and terminated by the addition of 100 μL of 1 M potassium phosphate pH 8, 30 mM EDTA quench buffer. A 100 μL aliquot of the reaction solution was then transferred to 96-well Millipore MultiScreen IP 0.45 μm PVDF filter plate (The filter plate was prewetted with 200 μL 100% ethanol, distilled water, and 1 M potassium phosphate pH 8, respectively). The filter plate was aspirated on a Millipore Manifold under vacuum and washed with 18×200 μL wash buffer containing 1 M potassium phosphate pH 8 and 1 mM ATP. After drying by aspiration and blotting, the plate was air dried in an incubator at 37° C. overnight. Packard TopCount adapter (Millipore) was then attached to the plate followed with addition of 120 μL Microscint 20 scintillation cocktail (Perkin Elmer) in each well. After the plate sealing, the radioactivity of the product was determined by scintillation counting on Topcount (Perkin-Elmer). IC50 determination was performed by fitting the curve of percent control activity versus the log of the inhibitor concentration using the GraphPad Prism 3 software. Compounds having and IC50 value of 10 μM or less are considered active.
- Assay organism: Homo sapiens
- Target name: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
- Target type: SINGLE PROTEIN
- Target organism: Homo sapiens

## Reference Molecule A
- Canonical SMILES: Cc1csc2nc(C(C)Nc3nc(N)nc4[nH]cnc34)c(-c3ccccc3)c(=O)n12
- Properties:
- ChEMBL ID: CHEMBL5803686
- Molecular weight: 418.49
- Heavy atoms: 30
- Hydrogen bond donors: 3
- Hydrogen bond acceptors: 8
- TPSA: 126.88
- LogP: 3.15
- Rotatable bonds: 4
- Ring count: 5
- Aromatic rings: 5
- Formal charge: 0
- Fraction Csp3: 0.15
- QED: 0.41

## Known Reference Result on This Endpoint
- Molecule A clean result: median pChEMBL = 7.12
- This result is provided as context for predicting Molecule B on the same endpoint.

## Reference Molecule A Other ChEMBL Evidence
- type IC50; relation =; value 75; units nM; pChEMBL 7.12; comment 788489

## Query Molecule B
- Canonical SMILES: Cc1csc2nc(C(C)Nc3nc(N)nc4[nH]cnc34)c(-c3cccc(F)c3)c(=O)n12
- Properties:
- ChEMBL ID: CHEMBL5986108
- Molecular weight: 436.48
- Heavy atoms: 31
- Hydrogen bond donors: 3
- Hydrogen bond acceptors: 8
- TPSA: 126.88
- LogP: 3.29
- Rotatable bonds: 4
- Ring count: 5
- Aromatic rings: 5
- Formal charge: 0
- Fraction Csp3: 0.15
- QED: 0.39

## Molecule Similarity
- Weighted Tanimoto: 0.84

Answer: 6.52