## Endpoint to Predict
- Endpoint scope: assay
- Measurement type: IC50
- Label type: continuous
- Binary semantics: pchembl
- Assay description: AKR1C3-Inhibitory Action: For the assay, 50 nl of a 100-fold concentrated solution of the test substance in DMSO were pipetted into a black low-volume 384-well microtitre plate (Greiner Bio-One, Frickenhausen, Germany), 2 μl of a solution of AKR1C3 in assay buffer [50 mM potassium phosphate buffer pH 7, 1 mM DTT, 0% (w/v) Pluronic F-127, 0.01% BSA (w/v) and protease inhibitor cocktail (complete, EDTA-free Protease Inhibitor Cocktail from Roche)] were added and the mixture was incubated for 15 min, in order to enable preliminary binding of the substances to the enzyme prior to the enzyme reaction. Then the enzyme reaction was started by adding 3 μl of a solution of NADPH (16.7 μM→final concentration in assay volume 5 μl is 10 μM) and coumberone (0.5 μM→final concentration in assay volume 5 μl is 0.3 μM) in assay buffer and the resulting mixture was incubated at 22° C. for the reaction time of 90 min. The concentration of the AKR1C3 was matched to the respective activity of the enzyme preparation and set such that the assay worked within the linear range. Typical concentrations were in the region of 1 nM. The reaction was stopped by adding 5 μl of a stop solution consisting of the inhibitor EM-1404 [F. Labrie et al. U.S. Pat. No. 6,541,463, 2003](2 μM→final concentration in assay volume 5 μl is 1 μM). Subsequently, the fluorescence of coumberol was measured at 520 nm (excitation at 380 nm) with a suitable measuring instrument (Pherastar from BMG Labtechnologies). The intensity of the fluorescence was used as a measure for the amount of coumberol formed and hence for the enzyme activity of AKR1C3. The data were normalized (enzyme reaction without inhibitor=0% inhibition; all other assay components but no enzyme=100% inhibition). Typically, the test substances were tested on the same microtitre plate at 11 different concentrations in the range from 20 μM to 96.8 μM (20 μM, 5.9 μM, 1.7 μM, 0.5 μM, 0.15 μM, 44 nM, 12.9 nM, 3.8 nM, 1.1 nM, 0.3 nM and 96.8 μM; the dilution series were prepared before the assay at the level of the 100-fold concentrated solution by serial 1:3 dilutions with 100% DMSO) in twin values for each concentration, and IC50 values were calculated by a 4-parameter fit.
- Assay organism: Homo sapiens
- Target name: Aldo-keto reductase family 1 member C3
- Target type: SINGLE PROTEIN
- Target organism: Homo sapiens

## Reference Molecule A
- Canonical SMILES: C[C@]12CC[C@@H]3c4ccc(C(=O)NCCc5nnn[nH]5)cc4CC[C@H]3[C@@H]1CC=C2c1cncc(F)c1
- Properties:
- ChEMBL ID: CHEMBL5988886
- Molecular weight: 472.57
- Heavy atoms: 35
- Hydrogen bond donors: 2
- Hydrogen bond acceptors: 5
- TPSA: 96.45
- LogP: 4.26
- Rotatable bonds: 5
- Ring count: 6
- Aromatic rings: 3
- Formal charge: 0
- Fraction Csp3: 0.44
- QED: 0.58

## Known Reference Result on This Endpoint
- Molecule A clean result: median pChEMBL = 8.3
- This result is provided as context for predicting Molecule B on the same endpoint.

## Reference Molecule A Other ChEMBL Evidence
- type IC50; relation =; value 5; units nM; pChEMBL 8.3; comment 503907

## Query Molecule B
- Canonical SMILES: C[C@H](O)CNC(=O)c1ccc2c(c1)CC[C@@H]1[C@@H]2CC[C@]2(C)C(c3cncc(F)c3)=CC[C@@H]12
- Properties:
- ChEMBL ID: CHEMBL5947988
- Molecular weight: 434.56
- Heavy atoms: 32
- Hydrogen bond donors: 2
- Hydrogen bond acceptors: 3
- TPSA: 62.22
- LogP: 4.88
- Rotatable bonds: 4
- Ring count: 5
- Aromatic rings: 2
- Formal charge: 0
- Fraction Csp3: 0.48
- QED: 0.72

## Molecule Similarity
- Weighted Tanimoto: 0.71

Answer: 8.22