ChEMBL ligand: CHEMBL107400 (GC-1, QRX-431, Sobetiroma, Sobetirome)
Thyroid hormone receptor-α/Thyroid hormone receptor alpha in Human [ChEMBL: CHEMBL1860] [GtoPdb: 588] [UniProtKB: P10827] There should be some charts here, you may need to enable JavaScript!
Thyroid hormone receptor-β/Thyroid hormone receptor beta in Human [ChEMBL: CHEMBL1947] [GtoPdb: 589] [UniProtKB: P10828] There should be some charts here, you may need to enable JavaScript!

DB	Assay description	Assay Type	Standard value	Standard parameter	Original value	Original units	Original parameter	Reference
Thyroid hormone receptor-α/Thyroid hormone receptor alpha in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL1860] [GtoPdb: 588] [UniProtKB: P10827]
ChEMBL	Binding affinity to human TRalpha1	B	8.6	pKd	2.5	nM	Kd	J Med Chem (2012) 55: 5649-5675 [PMID:22512468]
ChEMBL	Binding affinity against human Thyroid hormone receptor alpha-1 (hTRalpha1) using radiolabeled T3	B	8.74	pKd	1.8	nM	Kd	J Med Chem (2002) 45: 3310-3320 [PMID:12109914]
ChEMBL	Binding affinity of compound was determined against Thyroid hormone receptor alpha1	B	9.18	pKd	0.66	nM	Kd	J Med Chem (2003) 46: 3152-3161 [PMID:12825953]
GtoPdb	-	-	9.36	pKd	-	-	-	Mol Endocrinol (1990) 4: 227-34 [PMID:2158622]
ChEMBL	Displacement of [125I]3,5,3'-triiodo-L-thyronine from His-tagged human recombinant TRalpha1 by scintillation proximity assay	B	8.96	pKi	1.09	nM	Ki	J Med Chem (2008) 51: 7075-7093 [PMID:18975928]
ChEMBL	transactivation assay: Human epithelial kidney cells (HEK 293) were grown to 80% confluency in Dubelcco's modified Eagles 4.5 g/L glucose medium (high glucose DMEM) containing 10% fetal bovine serum, 50 units/mL penicillin and 50 μg/mL streptomycin. The cells were trypsinized with 0.25% trypsin, then diluted to 5×105 cells/mL with high glucose DMEM. Cells were added to Costar 3917 96-well plates at 5×104 cells/well, then incubated at 37° C. for 24 hours. 1.5 μg of TR expression vector (full length TRα-CMV or TRβ-CMV), 1.5 μg of a reporter plasmid containing a DR4 thyroid hormone response element (TRE) direct repeat spaced by four nucleotides (AGGTCAcaggAGGTCA) cloned upstream of a minimal thymidine kinase promoter linked to a firefly luciferase coding sequence, and 0.75 μg of a pRL-SV40 constitutive Renilla luciferase reporter plasmid were diluted into 540 μl of OptiMEM. 27 μL of lipofectamine reagent was diluted into 540 μL of OptiMEM. The plasmid and lipofectamine dilutions were combined then incubated at RT for 10 min. The mixture was then diluted into 4.29 mL of OptiMEM. Plates were washed with 100 μL of phosphate buffered saline (PBS) at pH 7.2 without magnesium or calcium chloride per well. Transfection mixtures were added at 50 μL per well, then incubated at 37° C. for 4 hours. Modified DME/F-12 Ham's medium without phenol red containing 15 mM HEPES and bicarbonate, 5 mM L-glutamine, charcoal-stripped FBS, 50 units/mL penicillin and 50 μg/mL streptomycin was added at 50 μL per well, then the plates were incubated at 37° C. for 20 hours. Drug stocks were made at 10 mM in DMSO, then serially diluted to 1× concentrations in DME/F-12 Ham's. Plates were washed with 100 μL of PBS (pH 7.2) per well. 100 μL of each drug stock was added to the wells in triplicate, and then the plates were incubated at 37° C. for 24 hours.Cells were assayed for luciferase activity using the Promega DualGlo kit. 50 μl of Luciferase Reagent were added per well, the plate was rocked for 15 min at RT, and then the plate was read for firefly luciferase activity. A 50 μl volume of Stop & Glo Reagent was added per well, then the plate was read for Renilla luciferase activity. Data normalized to Renilla internal control were analyzed with GraphPad Prism v.4a using the sigmoid dose response model to generate EC50 values±SEM.	B	7.13	pEC50	74.7	nM	EC50	US-10544075-B2. Derivatives of sobetirome (2020)
ChEMBL	Affinity On-target Cellular interaction: (Reporter gene assay (HEK293T cells)) EUB0000585a THRA	F	7.3	pEC50	50	nM	EC50	Affinity On-target Cellular Literature for EUbOPEN Chemogenomic Library
ChEMBL	Half-maximum activation of human Thyroid hormone receptor alpha-1 (hTRalpha1)	B	7.35	pEC50	45	nM	EC50	J Med Chem (2002) 45: 3310-3320 [PMID:12109914]
ChEMBL	Agonist activity at recombinant His6-tagged THR-alpha (unknown origin) expressed in Escherichia coli BL21(DE3) co-expressing RXR preincubated for 30 mins assessed as biotin-GRIP1 peptide recruitment by HTRF assay	B	8.52	pEC50	3	nM	EC50	J Med Chem (2014) 57: 3912-3923 [PMID:24712661]
Thyroid hormone receptor-β/Thyroid hormone receptor beta in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL1947] [GtoPdb: 589] [UniProtKB: P10828]
ChEMBL	Binding affinity to human TRbeta1	B	9.7	pKd	0.2	nM	Kd	J Med Chem (2012) 55: 5649-5675 [PMID:22512468]
ChEMBL	Binding affinity against human Thyroid hormone receptor beta 1 (hTRbeta1) using radiolabeled T3	B	10	pKd	0.1	nM	Kd	J Med Chem (2002) 45: 3310-3320 [PMID:12109914]
ChEMBL	Binding affinity of compound was determined against thyroid hormone receptor beta 1	B	10	pKd	0.1	nM	Kd	J Med Chem (2003) 46: 3152-3161 [PMID:12825953]
GtoPdb	-	-	10.17	pKd	-	-	-	Proc Natl Acad Sci USA (1977) 74: 3365-9 [PMID:269396]; Chem Biol (1998) 5: 299-306 [PMID:9653548]
ChEMBL	Displacement of [125I]3,5,3'-triiodo-L-thyronine His-tagged human recombinant TRbeta1 by scintillation proximity assay	B	9.49	pKi	0.32	nM	Ki	J Med Chem (2008) 51: 7075-7093 [PMID:18975928]
ChEMBL	Agonist activity at recombinant His6-tagged THR-beta (unknown origin) expressed in Escherichia coli BL21(DE3) co-expressing RXR preincubated for 30 mins assessed as biotin-GRIP1 peptide recruitment by HTRF assay	B	7.74	pEC50	18	nM	EC50	J Med Chem (2014) 57: 3912-3923 [PMID:24712661]
ChEMBL	Half-maximum activation of human Thyroid hormone receptor beta 1 (hTRbeta1)	B	8.15	pEC50	7	nM	EC50	J Med Chem (2002) 45: 3310-3320 [PMID:12109914]
ChEMBL	Affinity On-target Cellular interaction: (Reporter gene assay (HEK293T cells)) EUB0000585a THRB	F	8.15	pEC50	7	nM	EC50	Affinity On-target Cellular Literature for EUbOPEN Chemogenomic Library
ChEMBL	transactivation assay: Human epithelial kidney cells (HEK 293) were grown to 80% confluency in Dubelcco's modified Eagles 4.5 g/L glucose medium (high glucose DMEM) containing 10% fetal bovine serum, 50 units/mL penicillin and 50 μg/mL streptomycin. The cells were trypsinized with 0.25% trypsin, then diluted to 5×105 cells/mL with high glucose DMEM. Cells were added to Costar 3917 96-well plates at 5×104 cells/well, then incubated at 37° C. for 24 hours. 1.5 μg of TR expression vector (full length TRα-CMV or TRβ-CMV), 1.5 μg of a reporter plasmid containing a DR4 thyroid hormone response element (TRE) direct repeat spaced by four nucleotides (AGGTCAcaggAGGTCA) cloned upstream of a minimal thymidine kinase promoter linked to a firefly luciferase coding sequence, and 0.75 μg of a pRL-SV40 constitutive Renilla luciferase reporter plasmid were diluted into 540 μl of OptiMEM. 27 μL of lipofectamine reagent was diluted into 540 μL of OptiMEM. The plasmid and lipofectamine dilutions were combined then incubated at RT for 10 min. The mixture was then diluted into 4.29 mL of OptiMEM. Plates were washed with 100 μL of phosphate buffered saline (PBS) at pH 7.2 without magnesium or calcium chloride per well. Transfection mixtures were added at 50 μL per well, then incubated at 37° C. for 4 hours. Modified DME/F-12 Ham's medium without phenol red containing 15 mM HEPES and bicarbonate, 5 mM L-glutamine, charcoal-stripped FBS, 50 units/mL penicillin and 50 μg/mL streptomycin was added at 50 μL per well, then the plates were incubated at 37° C. for 20 hours. Drug stocks were made at 10 mM in DMSO, then serially diluted to 1× concentrations in DME/F-12 Ham's. Plates were washed with 100 μL of PBS (pH 7.2) per well. 100 μL of each drug stock was added to the wells in triplicate, and then the plates were incubated at 37° C. for 24 hours.Cells were assayed for luciferase activity using the Promega DualGlo kit. 50 μl of Luciferase Reagent were added per well, the plate was rocked for 15 min at RT, and then the plate was read for firefly luciferase activity. A 50 μl volume of Stop & Glo Reagent was added per well, then the plate was read for Renilla luciferase activity. Data normalized to Renilla internal control were analyzed with GraphPad Prism v.4a using the sigmoid dose response model to generate EC50 values±SEM.	B	8.55	pEC50	2.82	nM	EC50	US-10544075-B2. Derivatives of sobetirome (2020)

ChEMBL data shown on this page come from version 36:

Zdrazil B, Felix E, Hunter F, Manners EJ, Blackshaw J, Corbett S, de Veij M, Ioannidis H, Lopez DM, Mosquera JF, Magarinos MP, Bosc N, Arcila R, Kizilören T, Gaulton A, Bento AP, Adasme MF, Monecke P, Landrum GA, Leach AR. (2024). The ChEMBL Database in 2023: a drug discovery platform spanning multiple bioactivity data types and time periods. Nucleic Acids Res., 52(D1). DOI: 10.1093/nar/gkad1004. [EPMCID:10767899] [PMID:37933841]
Davies M, Nowotka M, Papadatos G, Dedman N, Gaulton A, Atkinson F, Bellis L, Overington JP. (2015) 'ChEMBL web services: streamlining access to drug discovery data and utilities.' Nucleic Acids Res., 43(W1). DOI: 10.1093/nar/gkv352. [EPMCID:25883136]