## Endpoint to Predict
- Endpoint scope: assay
- Measurement type: IC50
- Label type: continuous
- Binary semantics: pchembl
- Assay description: RORgammat (full-length human) Reporter Assay A: Cells used in this assay were transiently co-transfected with three different plasmids, one expressing the GAL4-DNA binding domain (DBD)-RORγt fusion protein under control of a CMV promoter (NH2-Gal4-DBD:RORC¿COOH in pCMV-BD, Stratagene #211342), and two reporter plasmids¿the firefly luciferase reporter under control of a GAL4 promoter (pFR-Luc 2× GAL4) and Renilla luciferase reporter under control of CMV promoter (pRL-CMV, Promega #E2261). The full-length coding sequence was used for human RORγt, i.e., nucleotides 142-1635 of human RORγt, transcript variant 2, NCBI Accession: NM_1001523.1 (SEQ ID NO: 1). HEK293T cells were plated at 35000 per well in 96-well plate in medium of MEM with 8.6% FBS. After 18-22 hours incubation, the transfection was carried out by using a PEI solution with 170.5 ng total DNA/well (50 ng pCMV-BD-ROR plus 20 ng of pFR-Luc reporter and 0.5 ng of pRL-CMV reporter plus 100 ng Carrier DNA (Clontech #630440) for each well). 4-6 hours after transfection, cells were treated with compounds for overnight in the medium with final concentration of FBS 1.1% and DMSO 0.1%. After overnight (16 to 20 hours) incubation, media were removed and cells were lysed with 20 μL 1× Passive Lysis Buffer (Promega) for 10-15 minutes. Luminescence was measured using a BMG LUMIstar OPTIMA plate reader, after addition of 75 μL/well firefly luciferase buffer, followed by 75 μL/well Renilla luciferase buffer. To calculate the effect of compounds on RORγt activity, firefly values were normalized against values of DMSO only and values of reference compound at saturating concentration, then further normalized against Renilla signals. IC50s were generated by plotting final Renilla normalized data against compound concentration and percent inhibition was calculated against DMSO control.
- Assay organism: Homo sapiens
- Target name: Nuclear receptor ROR-gamma
- Target type: SINGLE PROTEIN
- Target organism: Homo sapiens

## Reference Molecule A
- Canonical SMILES: C[C@H](NS(=O)(=O)c1ccc(-c2sc(-c3nnc(CC(C)(C)OC=O)o3)nc2CC2CCC2)c(Cl)c1)C(F)(F)F
- Properties:
- ChEMBL ID: CHEMBL5933672
- Molecular weight: 607.08
- Heavy atoms: 39
- Hydrogen bond donors: 1
- Hydrogen bond acceptors: 9
- TPSA: 124.28
- LogP: 5.58
- Rotatable bonds: 11
- Ring count: 4
- Aromatic rings: 3
- Formal charge: 0
- Fraction Csp3: 0.5
- QED: 0.28

## Known Reference Result on This Endpoint
- Molecule A clean result: median pChEMBL = 7.43
- This result is provided as context for predicting Molecule B on the same endpoint.

## Reference Molecule A Other ChEMBL Evidence
- type IC50; relation =; value 37; units nM; pChEMBL 7.43; comment 544152

## Query Molecule B
- Canonical SMILES: C[C@H](NS(=O)(=O)c1ccc(-c2sc(-c3nnc([C@H]4C[C@H](OC=O)C4)o3)nc2CC2CCC2)c(Cl)c1Cl)C(F)(F)F
- Properties:
- ChEMBL ID: CHEMBL5910552
- Molecular weight: 639.51
- Heavy atoms: 40
- Hydrogen bond donors: 1
- Hydrogen bond acceptors: 9
- TPSA: 124.28
- LogP: 6.16
- Rotatable bonds: 10
- Ring count: 5
- Aromatic rings: 3
- Formal charge: 0
- Fraction Csp3: 0.5
- QED: 0.26

## Molecule Similarity
- Weighted Tanimoto: 0.63

Answer: 7.57