. Author manuscript; available in PMC: 2019 Oct 30.

Published in final edited form as: Toxicol Sci. 2018 Jun 1;163(2):500–515. doi: 10.1093/toxsci/kfy049

Table 2.

Prioritized ToxCast Assay Targets for AOP Development as Identified by Assays Responding With the Greatest Number of Hits Below the Cytotoxic Burst Lower Bound (CTBlb; as Defined by the ACC) Relative to the Total Number of Chemicals Tested

Assay	Hits< CTBlb/Chemicals	Intended Target (Gene)	Target Name	Extant AOP(s) (AOP-Wiki)
NCCT_TPO_GUA_dn	0.327	TPO	Thyroperoxidase	42, 119, 159, 175
ATG_PXRE_CIS_up	0.327	NR1I2	Pregnane X receptor; PXR	8, 11, 60
ATG_ERE_CIS_up	0.138	ESR1	Estrogen receptor 1	29, 30, 146, 165^a, 167, 200
NCCT_TPO_AUR_dn	0.129	TPO	Thyroperoxidase	42, 119, 159, 175
ATG_PXR_TRANS_up	0.119	NR1I2	Pregnane X recpetor; PXR	8, 11, 60
ATG_NRF2_ARE_CIS_up	0.110	NFE2L2	Nuclear factor erythroid 2-related factor 2; NRF2	61, 232
ATG_ERa_TRANS_up	0.106	ESR1	Estrogen receptor 1	29, 30, 146, 165^a, 167, 200
ACEA_T47D_80hr_Positive	0.103	ESR1	Estrogen receptor 1	29, 30, 146, 165^a, 167, 200
TOX21_ERa_LUC_BG1_Agonist	0.096	ESR1	Estrogen receptor 1	29, 30, 146, 165^a, 167, 200
ATG_PPARg_TRANS_up	0.081	PPARG	Peroxisome proliferator-activated receptor gamma	72, 163, 206
ATG_VDRE_CIS_up	0.074	VDR	Vitamin D receptor
TOX21_ARE_BLA_agonist_ratio	0.070	NFE2L2	Nuclear factor erythroid 2-related factor 2; NRF2	61, 232
ATG_RXRb_TRANS_up	0.070	RXRB	Retinoid x receptor beta
NVS_NR_hPPARg	0.067	PPARG	Peroxisome proliferator-activated receptor gamma	72, 163, 206
NVS_TR_hDAT	0.063	SLC6A3	Sodium-dependent dopamine transporter
NVS_NR_hAR	0.060	AR	Androgen receptor	19, 23, 111, 117
OT_ER_ERaERb_0480	0.056	ESR1, ESR2	Estrogen receptor 1 and 2	29, 30, 146, 165^a, 167, 200
NVS_NR_hER	0.056	ESR1	Estrogen receptor 1	29, 30, 146, 165^a, 167, 200
OT_AR_ARELUC_AG_1440	0.056	AR	Androgen receptor	19, 23, 111, 117
ATG_Ahr_CIS_up	0.055	AHR	Aryl hydrocarbon receptor	21, 41, 57, 131 150
NVS_MP_rPBR	0.055	Tspo	Peripheral benzodiazepine receptor; translocator protein
ATG_PPRE_CIS_up	0.053	PPARA, PPARD, PPARG	Peroxisome proliferator-activated receptor, alpha, delta and gamma	6, 18, 37, 51, 72, 163, 166, 206
OT_ER_ERbERb_0480	0.053	ESR2	Estrogen receptor 2	29^a, 30^a, 146^a, 165^a, 167^a, 200^a
BSK_LPS_PGE2_down	0.052	PTGER2	Prostaglandin E receptor 2
TOX21_AhR_LUC_Agonist	0.051	AHR	Aryl hydrocarbon receptor	21, 41, 57, 131 150
NVS_NR_hGR	0.047	NR3C1	Glucocorticoid receptor	14, 64, 66, 71
NVS_MP_hPBR	0.047	TSPO	Peripheral benzodiazepine receptor; translocator protein
OT_ER_ERaERb_1440	0.046	ESR1, ESR2	Estrogen receptor 1 and 2	29, 30, 146, 165^a, 167, 200
OT_ER_ERbERb_1440	0.046	ESR2	Estrogen receptor 2	29^a, 30^a, 146^a, 165^a, 167^a, 200^a
NVS_NR_mERa	0.045	Esr1	Estrogen receptor 1	29, 30, 146, 165^a, 167, 200
NVS_OR_gSIGMA_NonSelective	0.042	Sigmar1	Sigma nonopioid intracellular receptor 1
NVS_NR_cAR	0.042	AR	Androgen receptor	19, 23, 111, 117
NVS_ENZ_hCK2a2b2	0.040	CSNK2A1	Casein kinase II alpha 1
OT_ERa_EREGFP_0120	0.039	ESR1	Estrogen receptor 1	29, 30, 146, 165^a, 167, 200
NVS_NR_bER	0.038	ESR1	Estrogen receptor 1	29, 30, 146, 165^a, 167, 200
ATG_DR5_CIS_up	0.038	RARA, RARB, RARG	Retinoic acid receptors alpha, beta, gamma
BSK_LPS_TNFa_down	0.038	TNF	Tumor necrosis factor
OT_ERa_EREGFP_0480	0.038	ESR1	Estrogen receptor 1	29, 30, 146, 165^a, 167, 200
BSK_3C_HLADR_down	0.037	HLA-DRA	Major histocompatability complex, class II, DRalpha
NVS_ENZ_hPDE5	0.037	PDE5A	Phosphodiesterase 5A
NVS_IC_rNaCh_site2	0.036	Scn1a	Sodium-voltage gated channel alpha subunit 1; Nav1.1	197
NVS_NR_hPR	0.035	PGR	Progesterone receptor
NVS_NR_hCAR_Antagonist	0.034	NR1I3	Constitutive androstane receptor (CAR)	58, 107
NVS_TR_hNET	0.033	SLC6A2	Norepinephrine transporter
NVS_ENZ_rMAOBC	0.033	Maob	Monoamine oxidase B
OT_ER_ERaERa_0480	0.033	ESR1	Estrogen receptor 1	29, 30, 146, 165^a, 167, 200
NVS_GPCR_h5HT7	0.032	HTR7	5-Hydroxytryptamine receptor 7	98^a, 97^a, 195^a, 204^a, 203^a
NVS_ENZ_rMAOAC	0.031	Maoa	Monoamine oxidase A
BSK_SAg_Eselectin_down	0.031	SELE	Eselectin; endothelial leukocyte adhesion molecule 1
ATG_PBREM_CIS_up	0.031	NR1I3	Constitutive androstane receptor (CAR)	58, 107
BSK_hDFCGF_CollagenIII_down	0.030	COL3A1	Collagen type III alpha 1 chain
BSK_hDFCGF_IP10_down	0.030	CXCL10	Chemokine ligand 10
BSK_hDFCGF_PAI1_down	0.030	SERPINE1	Serpin peptidase inhibitor, clade E
ATG_Oct_MLP_CIS_up	0.029	POU2F1	POU class 2 homeobox
NVS_ENZ_oCOX2	0.029	PTGS2	Cyclooxygenase 2	28, 63, 100–103, 228
TOX21_Aromatase_Inhibition	0.029	CYP19A1	Aromatase	7, 25, 153
BSK_CASM3C_IL6_down	0.029	IL6	Interleukin 6
NVS_GPCR_hM4	0.028	CHRM4	Cholinergic receptor muscarinic 4
OT_ER_ERaERa_1440	0.028	ESR1	Estrogen receptor 1	29, 30, 146, 165^a, 167, 200
ATG_SREBP_CIS_up	0.028	SREBF1	Sterol regulatory element binding transcription factor
NVS_ENZ_oCOX1	0.027	PTGS1	Cyclooxygenase 1	177, 227

The top 95th and 90th percentiles of assays are represented along with relevant AOPs in the AOP-Wiki (https:aopkb.org), as of October 2017. Intended targets and target names in bold font indicate potential novel MIE targets for AOP development.

AOP is related to the intended target, but the intended target is not specified in the MIE.