Nuclear Receptors Product Listing Edition 2 GBP

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1 uclear Product Listing Edition 2 GBP Kudzu Pueraria lobata A source of Daidzein uclear Products by Group: teroid ormone Group Thyroid ormone -like Group Retinoid X -like Group teroidogenic Factor-like Group

2 Tocris Product Listing eries Contents This listing contains over 150 products from Tocris, including a wide range of nuclear receptor agonists and antagonists available for each nuclear receptor group. Related products are also listed, alongside a selection of relevant scientific literature available from Introduction...3 teroid ormone Group...5 Androgen (AR)... 5 Estrogen (ER)... 5 Estrogen-related (ERR)... 7 Glucocorticoid (GR)... 7 Mineralocorticoid (MR)... 7 Progesterone (PR)... 7 Thyroid ormone -like Group...8 Constitutive Androstane (CAR)... 8 Farnesoid X (FXR)... 8 Liver X (LXR)... 8 Peroxisome Proliferator-activated (PPAR)... 8 Thyroid ormone -like Group (continued) Pregnane X (PXR)... 9 Retinoic Acid (RAR) Rev-Erb Thyroid ormone (TR) Vitamin D (VDR) Retinoid X -like Group epatocyte uclear Factor-4 (F-4) Retinoid X (RXR) teroidogenic Factor-like Group Liver omolog-1 (LR-1) teroidogenic Factor-1 (F-1) Related Products Aromatase (CYP19) Aryl ydrocarbon (AhR)

3 UCLEAR RECEPTR Introduction uclear receptors, also referred to as nuclear hormone receptors, are a subset of ligand-activated transcription factors that can bind to specific sites on DA and recruit transcription machinery, influencing gene expression. The 48 known nuclear receptors have been broadly classified into six main groups according to their sequence, with an additional, non-da binding group of receptors DAX-like receptors (group 0) also described (Figure 1). Figure 1 assification of uclear Group 1: Thyroid ormone -like Group 2: Retinoid X -like Group 3: teroid ormone Group 4: erve Growth Factor IB-like Group 5: teroidogenic Factor-like Group 6: Germ Cell uclear Factor Constitutive Androstane CUP-TF-like Androgen erve Growth Factor IB Liver omolog 1 Germ Cell uclear Factor Farnesoid X epatocyte uclear Factor-4 Estrogen euron-derived rphan 1 teroidogenic Factor 1 Liver X Retinoid X Estrogen-related uclear -related 1 PPAR Tailless-like Glucocorticoid Pregnane X Testicular Mineralocorticoid RAR-related rphan Progesterone Miscellaneous group Retinoic Acid Rev-Erb Group 0: DAX-like Thyroid ormone DAX1 Vitamin D P 3

4 Tocris Product Listing eries Introduction continued All nuclear receptors comprise five major domains: an -terminal regulatory domain, a DA-binding domain, a hinge region, a ligand-binding domain and a C-terminal domain (Figure 2). ome of these domains, such as the DA-binding domain, are highly conserved between nuclear receptors whereas others, for example the -terminal regulatory domain, are more variable. In addition to the phylogenetic classification of nuclear receptors (as described by the uclear omenclature Committee), nuclear receptors can also be separated into distinct types according to their functional characteristics. The principal difference between the types is in the location of the unbound nuclear receptor; prior to ligand binding, some nuclear receptors are located in the cytosol in a complex with heat shock proteins, whereas others exist in the nucleus where they bind to DA in a complex with transcriptional corepressors. The involvement of nuclear receptors in almost every cellular process, coupled with their innate ability to bind ligands and influence transcription, has led to significant drug discovery programs targeted at these receptors. Indeed, synthetic ligands for nuclear receptors such as estrogen receptors, glucocorticoid receptors and peroxisome proliferator-activated receptors, are currently used in the treatment of cancer, inflammatory disorders and metabolic disorders respectively. Further research into the physiological functions of these receptors may identify additional therapeutic targets within the nuclear receptor family. Figure 2 Canonical uclear tructure -terminal Domain DA-binding Domain Ligand-binding Domain C-terminal Domain inge Region A/B C D E F Key Functions Activation function-1 (AF-1) Ligand-independent transactivation Key Functions DA binding Dimerization Key Functions Activation function-2 (AF-2) Ligand binding Transactivation Dimerization uclear localization Coregulator binding ighly variable structure Function unknown For further information on nuclear receptor structure and function, please refer to Gronemeyer et al (2004) at Rev Drug Discov Tocris has a unique collection of products for nuclear receptors, from established biochemical standards to novel and exclusive licensed compounds. The information listed within is correct at the time of printing. For the latest information, and to request free scientific literature, please visit 4

5 UCLEAR RECEPTR teroid ormone Group teroid hormones and their receptors are involved in a vast range of biological processes, from development to cholesterol regulation. Certain members of this family, such as estrogen receptors and androgen receptors, are also important targets for cancer research due to their involvement in tumor cell proliferation. Category Cat. o. Product ame Description Unit ize GBP Androgen (AR) Agonists A-1 teroidal androgen receptor agonist 10 mg Testosterone Endogenous androgen receptor agonist 55 Antagonists 3389 Bicalutamide on-steroidal androgen receptor antagonist 10 mg Flutamide on-steroidal androgen receptor antagonist ilutamide Androgen receptor antagonist. rally active 100 mg PF on-steroidal androgen receptor antagonist 10 mg Modulators 3813 TFM-4A-1 elective androgen receptor modulator (ARM) 10 mg ther 4626 Andrographolide Inhibits F-κB; blocks AR expression Finasteride Type II 5α-reductase inhibitor; antiandrogen 55 6 Piperlongumine Induces apoptosis; depletes androgen receptors in prostate cancer cells 10 mg 115 Estrogen (ER) Agonists 1417 Daidzein ER agonist. Also induces cell cycle arrest DP ighly potent ERβ agonist 10 mg ERB 041 Potent ERβ agonist 10 mg α-estradiol Endogenous ER agonist β-estradiol Endogenous ER agonist 100 mg FERb 033 Potent and selective ERβ agonist 10 mg Liquiritigenin elective ERβ agonist 10 mg 1426 PPT ubtype-selective ERα agonist 10 mg (R,R)-TC Potent subtype-selective ligand; ERα agonist/erβ antagonist 10 mg WAY elective ERβ agonist 10 mg Key products for Estrogen Me F CF3 F F ERB 041 (4276) Potent ERβ agonist ICI 182,780 (1047) ER antagonist Liquiritigenin (3819) elective ERβ agonist 5

6 Tocris Product Listing eries Category Cat. o. Product ame Description Unit ize GBP Antagonists 0743 DPPE Antiestrogen; displays antiproliferative activity in vitro 10 mg Endoxifen Potent antiestrogen; ERα ligand 10 mg 1047 ICI 182,780 ER antagonist 1 mg 10 mg MPP ighly selective ERα antagonist 10 mg 2662 PTPP elective ERβ antagonist 10 mg 3224 RU Pure antiestrogen 10 mg Tamoxifen Antiestrogen; ER partial agonist/antagonist 100 mg (R,R)-TC Potent subtype-selective ligand; ERα agonist/erβ antagonist 10 mg ZK Potent ER antagonist 10 mg Ligands 1110 Genistein ER ligand. Also tyrosine kinase inhibitor 10 mg Zearalenone ER ligand; mycotoxin 10 mg Modulators 3999 Cyclofenil elective ER modulator 10 mg Raloxifene elective ER modulator Y 134 elective ERα modulator 10 mg 495 elective ERRβ and ERRγ Agonist GK 4716 Cat. o Glucocorticoid Agonist GK 9027 Cat. o CF 3 GK 4716 is a selective agonist at estrogen-related receptors ERRβ and ERRγ. The compound displays selectivity for ERRβ and ERRγ over ERRα and the classical estrogen receptors. F Et C 2 CF 3 GK 9027 is a glucocorticoid receptor agonist (pic 50 = 8). The compound inhibits production of the proinflammatory mediator IL-6 in vivo. Ph (old for research purposes under agreement from GlaxomithKline) Et F 3 C 2 C 2 6 C 2 C 2 Et

7 UCLEAR RECEPTR teroid ormone Group continued Category Cat. o. Product ame Description Unit ize GBP Estrogen-related (ERR) Agonists 2266 DY131 elective ERRβ and ERRγ agonist 10 mg GK 4716 elective ERRβ and ERRγ agonist 10 mg Antagonists 3928 XCT 790 elective ERRα antagonist/inverse agonist 10 mg 115 Glucocorticoid (GR) Agonists 2671 Budesonide ynthetic glucocorticoid; anti-inflammatory and 69 chemopreventive agent 3685 Corticosterone Endogenous glucocorticoid Dexamethasone Anti-inflammatory glucocorticoid 100 mg Fluticasone elective, high affinity glucocorticoid agonist 10 mg GK 9027 Glucocorticoid receptor agonist 10 mg ydrocortisone Adrenal glucocorticoid; immunosuppressant Mometasone ynthetic corticosteroid; anti-inflammatory agent 85 Antagonists 1479 Mifepristone Glucocorticoid and progesterone receptor antagonist 100 mg 69 Mineralocorticoid (MR) Agonists 3685 Corticosterone Endogenous glucocorticoid and mineralocorticoid 45 receptor agonist Antagonists 3934 Benidipine Mineralocorticoid receptor antagonist. Also blocks Ca 2+ channels 10 mg 3281 Canrenone Mineralocorticoid receptor antagonist Eplerenone elective mineralocorticoid receptor antagonist 10 mg 2970 RU Mineralocorticoid receptor antagonist 10 mg RU Potent, selective mineralocorticoid receptor antagonist 10 mg 2968 pironolactone Mineralocorticoid receptor antagonist 55 Progesterone (PR) Agonists 4833 Levonorgestrel ynthetic progesterone analog Mometasone ynthetic corticosteroid; progesterone receptor agonist Progesterone Endogenous progesterone receptor agonist 100 mg 55 Antagonists 1479 Mifepristone Progesterone and glucocorticoid receptor antagonist 100 mg

8 Tocris Product Listing eries Thyroid ormone -like Group Members of the thyroid hormone receptor-like group are involved in a wide range of cellular processes, including embryogenesis and cellular differentiation (retinoic acid receptors), bone homeostasis (vitamin D receptors) and the detection and clearance of foreign toxic substances (pregnane X receptors). Category Cat. o. Product ame Description Unit ize GBP Constitutive Androstane (CAR) Agonists 3683 CITC elective CAR agonist 10 mg TCPBP CAR agonist 10 mg Farnesoid X (FXR) Agonists 2563 Fexaramine Potent, selective farnesoid X receptor agonist 10 mg 2473 GW 4064 elective farnesoid X receptor agonist 10 mg Liver X (LXR) Agonists 2474 GW 3965 rally active liver X receptor agonist 1 mg 10 mg T Potent liver X receptor agonist 10 mg Peroxisome Proliferator-activated (PPAR) Agonists 1307 Ciglitazone elective PPARγ agonist 10 mg CP elective, high affinity PPARα agonist 10 mg Fenofibrate PPARα agonist GW 0742 ighly selective, potent PPARδ agonist 10 mg GW 1929 elective PPARγ agonist; orally active 10 mg 1677 GW 7647 ighly selective, potent PPARα agonist; orally active 10 mg L-165,041 Potent PPARδ agonist 10 mg 3831 LG RXR:PPAR agonist; sensitizes PPARγ 10 mg 2150 ntzdpa Potent, selective PPARγ partial agonist 10 mg leylethanolamide PPARα agonist. Also GPR55 agonist 10 mg Palmitoylethanolamide Endogenous lipid with PPARα agonist activity 10 mg Pioglitazone elective PPARγ agonist; antidiabetic agent 10 mg deoxy- - 12,14 -Prostaglandin J 2 Endogenous PPARγ agonist 1 mg elective PPARγ agonist; antidiabetic agent 10 mg 3965 Tesaglitazar PPARα/γ agonist 10 mg 3114 Troglitazone elective PPARγ agonist; antidiabetic agent 10 mg WY elective PPARα agonist 10 mg

9 UCLEAR RECEPTR Thyroid ormone -like Group continued Category Cat. o. Product ame Description Unit ize GBP Antagonists 1326 BADGE PPARγ antagonist 10 mg F 535 PPARγ/δ antagonist. Also inhibits Wnt/β-catenin signaling 10 mg GK 0660 elective PPARδ antagonist 10 mg GK 3787 Potent and selective PPARδ antagonist 10 mg 4618 GW 6471 PPARα antagonist 10 mg 1508 GW 9662 elective PPARγ antagonist 10 mg MK 886 PPARα antagonist. Also inhibits FLAP 10 mg R 202 elective PPARγ antagonist; antidiabetic and antiobesity agent 10 mg T ighly potent and selective PPARγ antagonist 10 mg Ligands 1110 Genistein PPARγ ligand. Also estrogen receptor ligand and EGFR 10 mg 45 inhibitor 4409 R 1664 igh affinity PPARγ ligand; blocks Cdk5-dependent PPARγ 10 mg phosphorylation 495 Pregnane X (PXR) Agonists 4245 Meclizine Pregnane X receptor agonist. Also 1 antagonist Rifampicin Pregnane X receptor agonist; antibiotic R Pregnane X receptor agonist 10 mg Key Products for PPAR CF 3 Et C 2 Pioglitazone (4124) elective PPARγ agonist; antidiabetic agent Tesaglitazar (3965) PPARα/γ agonist GK 3787 (3961) Potent and selective PPARδ antagonist Ph 2 C Et F 3 C 2 GW 6471 (4618) R 1664 (4409) PPARα antagonist igh affinity PPARγ ligand 9

10 Tocris Product Listing eries Category Cat. o. Product ame Description Unit ize GBP Retinoic Acid (RAR) Agonists 4046 AC RARβ2 agonist 10 mg AC elective RARβ2 agonist 10 mg Adapalene RARβ and RARγ agonist 10 mg AM 580 Retinoic acid analog; RARα agonist 10 mg 3507 AM 80 RARα agonist; anticancer 10 mg BM 453 ynthetic retinoid. RARβ agonist; also RARα and RARγ 10 mg antagonist 3505 BM 753 RARα-selective agonist 10 mg BM 961 elective RARγ agonist 10 mg CD 1530 Potent and selective RARγ agonist 10 mg 1549 CD 437 RARγ-selective agonist 10 mg 2020 Ch 55 Potent RAR agonist 10 mg Retinoic acid Endogenous retinoic acid receptor agonist TTPB Retinoic acid analog; RAR agonist 10 mg Antagonists 3660 BM elective RARα antagonist 10 mg BM 453 ynthetic retinoid. RARβ agonist; also RARα and RARγ 10 mg antagonist 3509 BM 493 Pan-RAR inverse agonist 10 mg CD 2665 elective RARβ/γ antagonist 10 mg 3823 ER elective RARα antagonist 10 mg LE elective RARβ antagonist 10 mg MM 13 RARγ-selective antagonist 10 mg 495 ther 4011 EC 23 ynthetic retinoid; induces differentiation of stem cells 10 mg 1396 Fenretinide ynthetic retinoid; potent anticancer agent 10 mg Tazarotene -selective retinoid; binds RARβ and RARγ 10 mg

11 UCLEAR RECEPTR Thyroid ormone -like Group continued Category Cat. o. Product ame Description Unit ize GBP Rev-Erb Agonists 3663 GK 4112 elective Rev-Erbα agonist 10 mg Antagonists 4463 R 8278 Rev-Erbα antagonist 10 mg 459 Thyroid ormone (TR) Agonists 4554 GC 1 igh affinity TRα and TRβ agonist; thyromimetic 10 mg Vitamin D (VDR) Agonists 2551 Calcitriol Active metabolite of vitamin D 3 ; VDR agonist 50 µg Doxercalciferol Vitamin D 2 analog; VDR agonist 1 mg 3993 EB 1089 VDR agonist 1 mg 3970 Ercalcitriol Active metabolite of vitamin D 2 ; VDR agonist 1 mg ther 9 Alfacalcidol Prodrug of vitamin D 3 (Cat. o. 6) 1 mg 4036 Calcifediol Prohormone of calcitriol (Cat. o. 2551). Major circulating 1 mg 85 form of vitamin D 2700 Calcipotriol Vitamin D 3 analog 10 mg Ercalcidiol Metabolite of vitamin D 2 1 mg xacalcitriol on-calcemic vitamin D 3 (Cat. o. 6) analog 1 mg 7 Tacalcitol ynthetic vitamin D 3 (Cat. o. 6) analog 1 mg Vitamin D 3 Precursor of calcifediol (Cat. o. 4036). aturally occurring form of vitamin D 39 Key Products for Thyroid ormone -like Group C 2 MM 13 (3822) RARγ-selective antagonist C 2 Et CITC (3683) elective CAR agonist C 2 Me BM 453 (3409) RARβ agonist; RARα and RARγ antagonist R 8278 (4463) Rev-Erbα antagonist Me Me C 2 Calcipotriol (2700) Vitamin D 3 analog GC 1 (4554) igh affinity TRα and TRβ agonist; thyromimetic 11

12 Tocris Product Listing eries Retinoid X -like Group This group of nuclear receptors is involved in diverse biological processes, including development, metabolism and stem cell differentiation. Members of this family have also been linked to diseases: retinoid X receptor agonists exhibit anticancer activity, whilst mutations in hepatocyte nuclear factor-4 have been associated with type II diabetes mellitus. Category Cat. o. Product ame Description Unit ize GBP epatocyte uclear Factor-4 (F-4) Antagonists 4641 BI 6015 epatocyte nuclear factor-4α receptor antagonist 10 mg 469 Retinoid X (RXR) Agonists 3302 CD 3254 Potent and selective RXRα agonist 10 mg 3687 Docosahexaenoic acid RXR agonist 100 mg Fluorobexarotene RXR agonist 10 mg LG RXR:PPAR agonist 10 mg 3411 R Pan RXR agonist 10 mg 50mg 479 Antagonists 3912 X 531 RXR antagonist 10 mg UVI 3003 RXR antagonist 10 mg 115 Modulators 3508 LG elective RXR modulator 10 mg 535 ther 3913 X 630 RXR synergist 10 mg epatocyte uclear Factor-4α Antagonist BI 6015 Cat. o Retinoid X Antagonist X 531 Cat. o C 2 BI 6015 is a hepatocyte nuclear factor-4α (F-4α) antagonist that represses expression of known F-4 target genes. The compound decreases F-4α-DA binding and exhibits cytotoxicity in a range of human tumor cell lines, including human hepatocellular carcinoma. 2 X 531 is a potent RXR antagonist (IC 50 = 18 nm). The compound suppresses docosahexaenoic acid-induced adipose differentiation-related protein (ADRP) expression in BeWo cells. (old under license) 12

13 teroidogenic Factor-like Group UCLEAR RECEPTR teroidogenic factor-like receptors regulate the differentiation and function of endocrine glands. They are classed as orphan receptors because no endogenous ligands for these receptors have been identified. Details of their transcriptional activity and how these receptors are regulated also remain unclear. Category Cat. o. Product ame Description Unit ize GBP Liver omolog-1 (LR-1) Agonists 4378 DLPC elective LR-1 agonist 39 teroidogenic Factor-1 (F-1) Antagonists 3043 AC F-1 inverse agonist 10 mg ID elective steroidogenic factor-1 (F-1, R5A1) antagonist 10 mg teroidogenic Factor-1 Inverse Agonist AC Cat. o elective teroidogenic Factor-1 Antagonist ID Cat. o AC is a selective inverse agonist at the orphan nuclear receptor steroidogenic factor-1 (F-1) (IC 50 = nm). The compound displays no activity at estrogen, LR-1, RR, ERR or urr receptors. AC inhibits FRE-mediated transcription. Et ID is a selective steroidogenic factor-1 (F-1, R5A1) antagonist (IC 50 values are 0.76, >33 and >33 µm at F-1, RRα and VP16 receptors respectively). The compound inhibits F-1-dependent luciferase expression in EK293T cells in vitro (IC 50 = 30 nm). Me Me 13

14 Tocris Product Listing eries Related Products uclear receptor function is also modulated by other receptors and enzymes that affect steroid hormone metabolism, such as aromatase and retinoic acid 4-hydrolase. The aryl hydrocarbon receptor also influences the function of steroid hormone receptors (e.g. estrogen receptors) through a number of different mechanisms. Category Cat. o. Product ame Description Unit ize GBP Aromatase (CYP19) Inhibitors 3388 Anastrozole Potent aromatase inhibitor 10 mg Letrozole Potent, reversible non-steroidal aromatase inhibitor 10 mg Liarozole Aromatase inhibitor. Also blocks retinoic acid metabolism 10 mg YM 511 Potent aromatase inhibitor 10 mg Aryl ydrocarbon (AhR) Agonists 1803 ITE AhR endogenous agonist 10 mg Antagonists 3858 C AhR antagonist 10 mg 50mg ,2ʹ,4ʹ-Trimethoxyflavone AhR antagonist 10 mg 50mg Ligands 3 L-Kynurenine Tryptophan catabolite; endogenous AhR ligand 39 Modulators 4628 DiMF elective AhR modulator 10 mg 435 Key uclear Related Products Me Liarazole (2705) Aromatase inhibitor. Also blocks retinoic acid metabolism ITE (1803) Aryl hydrocarbon receptor endogenous agonist C (3858) Potent aryl hydrocarbon receptor antagonist Prices are correct for For a full product listing please visit 14

UCLEAR RECEPTR Related literature from Tocris that you may be interested in: Pharmacology of Retinoid Alexander R.

of cancer. Due to this, there has been a tremendous effort to develop safe and receptor-selective compounds.

Cancer Research Product Guide ver 350 Products for Cancer Research ur updated guide contains products with supporting information and figures to

Invasion and Metastasis Cardiovascular Research Product Guide ver 250 Products for Cardiovascular Research ur new guide contains products with

Atherosclerosis Myocardial Infarction and Ischemia/Reperfusion Injury Arrhythmias eart Failure Peptide ormone Product Listing ver 200 Products for

15 UCLEAR RECEPTR Related literature from Tocris that you may be interested in: Pharmacology of Retinoid Alexander R. Moise, University of Kansas Retinoid signaling can induce cellular differentiation or apoptosis, which is particularly relevant in the treatment of cancer. Due to this, there has been a tremendous effort to develop safe and receptor-selective compounds. This review summarizes the nature of retinoid receptors, their isotype and isoform variants and modulation of retinoid signaling. Cancer Research Product Guide ver 350 Products for Cancer Research ur updated guide contains products with supporting information and figures to illustrate the relevance of each target within the areas of: ignaling Cell Cycle and DA Damage Repair Cell Death and Drug Resistance Angiogenesis Invasion and Metastasis Cardiovascular Research Product Guide ver 250 Products for Cardiovascular Research ur new guide contains products with supporting information and figures to illustrate the relevance of each target within the areas of: ypertension Thrombosis and emostasis Atherosclerosis Myocardial Infarction and Ischemia/Reperfusion Injury Arrhythmias eart Failure Peptide ormone Product Listing ver 200 Products for Peptide ormone ur new product listing contains products for key peptide hormone receptors including: Angiotensin Ghrelin xytocin omatostatin Vasopressin To download or request copies, please visit

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Nuclear Receptor Monoclonal Antibodies

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