## Endpoint to Predict
- Endpoint scope: assay
- Measurement type: EC50
- Label type: continuous
- Binary semantics: pchembl
- Assay description: Biological Testing: The biochemical assay tests competitive binding of compounds to recombinant Hsp90α protein and also Hsp90 found in cell specific complexes, and uses a fluorescence polarization method.7,23 When using cell lysates instead of recombinant protein, the assay measures binding to average Hsp90 population found in cell specific complexes.7 The cellular assays measure two specific biological effects observed upon addition of known Hsp90 inhibitors to cancer cells: (a) degradation of the tyrosine kinase Her224 and (b) mitotic block in Rb-defective cells.25 Overexpression of the receptor tyrosine kinase Her2 in SKBr3 breast cancer cells leads to Akt activation which in turn promotes cell survival. Hsp90 uniquely stabilizes Her2 via interaction with its kinase domain and an Hsp90 inhibitor induces Her2 degradation by disrupting the Her2/Hsp90 association.24 We have previously reported a fast microtiter immunoassay able of quantifying cellular levels of Her2 following drug treatments.26 This assay is used here to differentiate the Her2-degradative potential of the above synthesized purines. Hsp90 inhibitors are also known to cause cells lacking functional RB to progress normally through G1 and arrest in mitosis.25 Thus, another assay used here to test cellular Hsp90 inhibition relies on assessing the anti-mitotic potential of synthesized purines. The assay is a microtiter immunoassay and uses an antibody against a mitotically phosphorylated form of nucleolin to detect cells in mitosis.27 This antibody (Tg-3), originally described as a marker of Alzheimer's disease, is highly specific for mitotic cells, Tg-3 immunofluorescence being >50-fold more intense in mitotic cells than in interphase cells.28 In addition, the cytotoxicity of these agents against SKBr3 breast cancer cells was determined. A selected number of most active purines were also tested for possible toxicity against a normal cell line, renal proximal tubular epithelial cells (RPTEC).
- Assay organism: Homo sapiens
- Target name: Heat shock protein HSP 90-alpha
- Target type: SINGLE PROTEIN
- Target organism: Homo sapiens

## Reference Molecule A
- Canonical SMILES: CC(C)NCCCN1c2nc(F)ncc2NC1Sc1c(Br)ccc2c1O2
- Properties:
- ChEMBL ID: CHEMBL5919279
- Molecular weight: 440.34
- Heavy atoms: 26
- Hydrogen bond donors: 2
- Hydrogen bond acceptors: 7
- TPSA: 65.61
- LogP: 4.18
- Rotatable bonds: 7
- Ring count: 4
- Aromatic rings: 2
- Formal charge: 0
- Fraction Csp3: 0.41
- QED: 0.32

## Known Reference Result on This Endpoint
- Molecule A clean result: median pChEMBL = 7.41
- This result is provided as context for predicting Molecule B on the same endpoint.

## Reference Molecule A Other ChEMBL Evidence
- type EC50; relation =; value 38.8; units nM; pChEMBL 7.41; comment 606403

## Query Molecule B
- Canonical SMILES: C#CCCCN1c2ncncc2NC1Sc1c(I)ccc2c1O2
- Properties:
- ChEMBL ID: CHEMBL6047878
- Molecular weight: 436.28
- Heavy atoms: 23
- Hydrogen bond donors: 1
- Hydrogen bond acceptors: 6
- TPSA: 53.58
- LogP: 3.91
- Rotatable bonds: 5
- Ring count: 4
- Aromatic rings: 2
- Formal charge: 0
- Fraction Csp3: 0.25
- QED: 0.28

## Molecule Similarity
- Weighted Tanimoto: 0.48

Answer: 8