## Endpoint to Predict
- Endpoint scope: assay
- Measurement type: IC50
- Label type: continuous
- Binary semantics: pchembl
- Assay description: R132H IDH1 Enzymatic Assay: Each test compound (10 mM stock in DMSO) is diluted in DMSO to make a 10-point, 3-fold dilution series. 125 nL of each dilution or DMSO alone is dispensed to a 384-well Greiner Lumitrac 200 assay plate using an Echo® Liquid Handler. To each well of the plate is added 20 uL of enzyme in assay buffer or assay buffer alone. Assay buffer consists of 50 mM sodium phosphate, pH 7, 50 mM magnesium chloride, 50 mM sodium chloride, and 0.01% (w/v) bovine serum albumin. When present, the R132H mutant IDH1 enzyme is at a working concentration of 1.88 nM (final concentration in assay of 1.5 nM). The assay plate is allowed to incubate for 30 minutes at room temperature and 5 uL of 5× substrate mixture (2.5 uM nicotinamide adenine dinucleotide phosphate, 100 uM adenosine diphosphate, 7.5 mM glyceraldehyde-3-phosphate, 7.5 ug/mL of spinach glyceraldehyde-3-phosphate dehydrogenase, 25 nM phosphoglycerate kinase, and 5 mM alpha-ketoglutarate in assay buffer) is added to all wells. The reaction plate is incubated for 60 minutes followed by addition of 25 uL of Promega Kinase-GLO reagent to all wells and 10-minute incubation.Luminescence is measured using a PerkinElmer Envision plate reader. The percent activity of each dilution is determined as the ratio of background corrected signal to the background corrected signal of wells receiving only DMSO. IC50 values are determined by fitting percent activity data to a four-parameter logistic dose response equation. The IC50 values of the exemplified compounds are included in the tables above in Examples section.Using the above biological assay, all compounds in the examples have IC50 of about 1 nM to about 40,000 nM, or more specifically, about 1 nM to about 20,000 nM, or even more specifically, about 5 nM to about 15,000 nM, or even more specifically, about 5 nM to about 10,000 nM, or even more specifically, about 5 nM to about 5,000 nM, or still more specifically, about 5 nM to about 1,000 nM. Such a result is indicative of the intrinsic activity of the compounds in use as an inhibitor of a mutant IDH1 enzyme. Specific IC50 activity data for the exemplified compounds disclosed herein is provided in the following table.
- Target name: Isocitrate dehydrogenase [NADP] cytoplasmic
- Target type: SINGLE PROTEIN
- Target organism: Homo sapiens

## Reference Molecule A
- Canonical SMILES: CCOC1CC2(C1)CC(C(=O)N1Cc3cccnc3Nc3ccc(N4CCOCC4)cc31)C2
- Properties:
- ChEMBL ID: CHEMBL5865506
- Molecular weight: 448.57
- Heavy atoms: 33
- Hydrogen bond donors: 1
- Hydrogen bond acceptors: 6
- TPSA: 66.93
- LogP: 4.1
- Rotatable bonds: 4
- Ring count: 6
- Aromatic rings: 2
- Formal charge: 0
- Fraction Csp3: 0.54
- QED: 0.76

## Known Reference Result on This Endpoint
- Molecule A clean result: median pChEMBL = 5.82
- This result is provided as context for predicting Molecule B on the same endpoint.

## Reference Molecule A Other ChEMBL Evidence
- type IC50; relation =; value 1504; units nM; pChEMBL 5.82; comment 549079

## Query Molecule B
- Canonical SMILES: CO[C@H]1C2CC3CC1C[C@@](C(=O)N1Cc4cccnc4Nc4ccc(N5CCOCC5)cc41)(C3)C2
- Properties:
- ChEMBL ID: CHEMBL5956316
- Molecular weight: 474.61
- Heavy atoms: 35
- Hydrogen bond donors: 1
- Hydrogen bond acceptors: 6
- TPSA: 66.93
- LogP: 4.35
- Rotatable bonds: 3
- Ring count: 8
- Aromatic rings: 2
- Formal charge: 0
- Fraction Csp3: 0.57
- QED: 0.71

## Molecule Similarity
- Weighted Tanimoto: 0.61

Answer: 5