## Endpoint to Predict
- Endpoint scope: assay
- Measurement type: IC50
- Label type: continuous
- Binary semantics: pchembl
- Assay description: LanthaScreen Assay: The LRRK2 kinase activity reported herein as IC50 values was determined with LanthaScreen technology from Life Technologies Corporation (Carlsbad, Calif.) using GST-tagged truncated human mutant G2019S LRRK2 in the presence of the fluorescein-labeled peptide substrate LRRKtide, also from Life Technologies. The data presented for the Km ATP LanthaScreen Assay represents mean IC50 values based on several test results and may have reasonable deviations depending on the specific conditions and reagents used. Assays were performed in the presence of 134 μM ATP (Km ATP). Upon completion, the assay was stopped and phosphorylated substrate detected with a terbium (Tb)-labeled anti-pERM antibody (cat. no. PV4898). The compound dose response was prepared by diluting a 10 mM stock of compound to a maximum concentration of 9.99 M in 100% dimethylsulfoxide followed by custom fold serial dilution in dimethylsulfoxide nine times. Twenty nanoliters of each dilution was spotted via a Labcyte Echo onto a 384-well black-sided plate (Corning 3575) followed by 15 μl of a 1.25 nM enzyme solution in 1× assay buffer (50 mM Tris pH 8.5, 10 mM MgCl2, 0.01% Brij-35, 1 mM EGTA, 2 mM dithiothreitol, 0.05 mM sodium orthovanadate). Following a 15-minute incubation at room temperature, the kinase reaction was started with the addition of 5 μl of 400 nM fluorescein-labeled LRRKtide peptide substrate and 134 μM ATP solution in 1× assay buffer. The reaction was allowed to progress at ambient temperature for 90 minutes. The reaction was then stopped by the addition of 20 μl of TR-FRET Dilution Buffer (Life Technologies, Carlsbad, Calif.) containing 2 nM Tb-labeled anti-phospho LRRKtide antibody and 10 mM EDTA (Life Technologies, Carlsbad, Calif.). After an incubation of 1 hour at room temperature, the plate was read on an EnVision multimode plate reader (Perkin Elmer, Waltham, Mass.) with an excitation wavelength of 337 nm (Laser) and a reading emission at both 520 and 495 nm. Compound IC50s were interpolated from nonlinear regression best fits of the log of the final compound concentration, plotted as a function of the 520/495-nm emission ratio using Activity base. Abase uses a 4 parameter (4P) logistic fit based on the Levenberg-Marquardt algorithm.
- Target name: Leucine-rich repeat serine/threonine-protein kinase 2
- Target type: SINGLE PROTEIN
- Target organism: Homo sapiens

## Reference Molecule A
- Canonical SMILES: Cc1nc(N2CC3(C(C)(C)O)CC2C3)cc(-n2ncc3ccc(C4(C#N)CC45CC5)cc32)n1
- Properties:
- ChEMBL ID: CHEMBL5986603
- Molecular weight: 440.55
- Heavy atoms: 33
- Hydrogen bond donors: 1
- Hydrogen bond acceptors: 6
- TPSA: 90.86
- LogP: 3.81
- Rotatable bonds: 4
- Ring count: 8
- Aromatic rings: 3
- Formal charge: 0
- Fraction Csp3: 0.54
- QED: 0.66

## Known Reference Result on This Endpoint
- Molecule A clean result: median pChEMBL = 8.95
- This result is provided as context for predicting Molecule B on the same endpoint.

## Reference Molecule A Other ChEMBL Evidence
- type IC50; relation =; value 2.1; units nM; pChEMBL 8.68; comment 1104562
- type IC50; relation =; value 0.6; units nM; pChEMBL 9.22; comment 1104563

## Query Molecule B
- Canonical SMILES: Cc1cc(-n2ncc3ccc([C@]4(C#N)CC45CC5)cc32)nc(C)n1
- Properties:
- ChEMBL ID: CHEMBL5618927
- Molecular weight: 315.38
- Heavy atoms: 24
- Hydrogen bond donors: 0
- Hydrogen bond acceptors: 4
- TPSA: 67.39
- LogP: 3.38
- Rotatable bonds: 2
- Ring count: 5
- Aromatic rings: 3
- Formal charge: 0
- Fraction Csp3: 0.37
- QED: 0.73

## Molecule Similarity
- Weighted Tanimoto: 0.65

Answer: 8.28