## Endpoint to Predict
- Endpoint scope: assay
- Measurement type: IC50
- Label type: continuous
- Binary semantics: pchembl
- Assay description: PI3K Enzyme Assay A1: PI3-Kinase luminescent assay kit including lipid kinase substrate, D-myo-phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2)D (+)-sn-1,2-di-O-octanoylglyceryl, 3-O-phospho linked (PIP2), biotinylated I(1,3,4,5)P4, PI(3,4,5)P3 Detector Protein, was purchased from Echelon Biosciences (Salt Lake City, Utah). AlphaScreen GST Detection Kit including donor and acceptor beads was purchased from PerkinElmer Life Sciences (Waltham, Mass.). PI3Kδ (p110δ/p85α) was purchased from Millipore (Bedford, Mass.). ATP, MgCb, DTT, EDTA, HEPES and CHAPS were purchased from Sigma-Aldrich (St. Louis, Mo.).AlphaScreen Assay for PI3KδThe kinase reaction was conducted in 384-well REMP plate from Thermo Fisher Scientific in a final volume of 40 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 2%. The PI3K assays were carried out at room temperature in 50 mM HEPES, pH 7.4, 5 mM MgCl2, 50 mM NaCl, 5 mM DTT and CHAPS 0.04%. Reactions were initiated by the addition of ATP, the final reaction mixture consisted of 20 μM PIP2, 20 μM ATP, 1.2 nM PI3Kδ were incubated for 20 min. 10 μL of reaction mixture was then transferred to 5 μL 50 nM biotinylated I(1,3,4,5)P4 in quench buffer: 50 mM HEPES pH 7.4, 150 mM NaCl, 10 mM EDTA, 5 mM DTT, 0.1% Tween-20, followed with the addition of 10 μL AlphaScreen donor and acceptor beads suspended in quench buffer containing 25 nM PI(3,4,5)P3 detector protein. The final concentration of both donor and acceptor beads is 20 mg/ml. After plate sealing, the plate was incubated in a dark location at room temperature for 2 hours. The activity of the product was determined on Fusion-alpha microplate reader (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.
- 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: CCC(Nc1ncnc2[nH]cnc12)c1nc2cccc(C)n2c(=O)c1-c1cccc(F)c1
- Properties:
- ChEMBL ID: CHEMBL5901894
- Molecular weight: 429.46
- Heavy atoms: 32
- Hydrogen bond donors: 2
- Hydrogen bond acceptors: 6
- TPSA: 100.86
- LogP: 4.04
- Rotatable bonds: 5
- Ring count: 5
- Aromatic rings: 5
- Formal charge: 0
- Fraction Csp3: 0.17
- QED: 0.44

## Known Reference Result on This Endpoint
- Molecule A clean result: median pChEMBL = 6.52
- This result is provided as context for predicting Molecule B on the same endpoint.

## Reference Molecule A Other ChEMBL Evidence
- type IC50; relation =; value 300; units nM; pChEMBL 6.52; comment 788475

## Query Molecule B
- Canonical SMILES: Cc1csc2nc(C(C)Nc3ncnc4[nH]cnc34)c(-c3ccccn3)c(=O)n12
- Properties:
- ChEMBL ID: CHEMBL6014786
- Molecular weight: 404.46
- Heavy atoms: 29
- Hydrogen bond donors: 2
- Hydrogen bond acceptors: 8
- TPSA: 113.75
- LogP: 2.97
- Rotatable bonds: 4
- Ring count: 5
- Aromatic rings: 5
- Formal charge: 0
- Fraction Csp3: 0.16
- QED: 0.47

## Molecule Similarity
- Weighted Tanimoto: 0.48

Answer: 7.12