## Endpoint to Predict
- Endpoint scope: assay
- Measurement type: IC50
- Label type: continuous
- Binary semantics: pchembl
- Assay description: In Vitro Assays for IDH2m R140Q Inhibitors: Compounds are assayed for IDH2 R140Q inhibitory activity through a cofactor depletion assay. Compounds are preincubated with enzyme and cofactor, then the reaction is started by the addition of α-KG, and allowed to proceed for 60 minutes under conditions previously demonstrated to be linear. The reaction is terminated by the addition of a second enzyme, diaphorase, and a corresponding substrate, resazurin. Diaphorase reduces resazurin to the highly fluorescent resorufin with the concomitant oxidation of NADPH to NADP, both halting the IDH2 reaction by depleting the available cofactor pool and facilitating quantitation of the amount of cofactor remaining after a specific time period through quantitative production of an easily detected fluorophore.Specifically, into each of 12 wells of a 384-well plate, 1 μl of 50× compound dilution series is placed, followed by the addition of 40 μl of buffer (50 mM potassium phosphate (K2HPO4), pH 7.5; 150 mM NaCl; 10 mM MgCl2, 10% glycerol, 0.05% bovine serum albumin, 2 mM beta-mercaptoethanol) containing 0.39 μg/ml IDH2 R140Q protein, 5 uM NADPH and 750 uM NADP. The test compound is then incubated for 16 hrs at room temperature with the enzyme and cofactors before starting the IDH2 reaction with the addition of 10 μl of substrate mix containing 8 mM α-KG (final concentration 1.6 mM) in the buffer described above. After a further 1 hour of incubation at room temperature, the reaction is halted and the remaining NADPH measured through conversion of resazurin to resorufin by the addition of 25 μl Stop Mix (36 μg/ml diaphorase enzyme and 60 μM resazurin; in buffer). After one minute of incubation the plate is read on a plate reader at Ex544/Em590.
- Target name: Isocitrate dehydrogenase [NADP], mitochondrial
- Target type: SINGLE PROTEIN
- Target organism: Homo sapiens

## Reference Molecule A
- Canonical SMILES: CC(COC(C)C)Nc1nc(N[C@H](C)C2CC2)nc(-c2cccc(C(F)(F)F)n2)n1
- Properties:
- ChEMBL ID: CHEMBL4286667
- Molecule type: Small molecule
- Molecular weight: 424.47
- Heavy atoms: 30
- Hydrogen bond donors: 2
- Hydrogen bond acceptors: 7
- TPSA: 84.85
- LogP: 4.39
- Rotatable bonds: 9
- Ring count: 3
- Aromatic rings: 2
- Formal charge: 0
- Fraction Csp3: 0.6
- QED: 0.62

## 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 533805

## Query Molecule B
- Canonical SMILES: CC(C)(C#N)CNc1nc(Nc2ccnc(C(C)(F)F)c2)nc(-c2cccc(C(F)(F)F)n2)n1
- Properties:
- ChEMBL ID: CHEMBL4278435
- Molecule type: Small molecule
- Molecular weight: 478.43
- Heavy atoms: 34
- Hydrogen bond donors: 2
- Hydrogen bond acceptors: 8
- TPSA: 112.3
- LogP: 5.16
- Rotatable bonds: 7
- Ring count: 3
- Aromatic rings: 3
- Formal charge: 0
- Fraction Csp3: 0.33
- QED: 0.45

## Molecule Similarity
- Weighted Tanimoto: 0.37

Answer: 7.12