Literature DB >> 26650443

The Concise Guide to PHARMACOLOGY 2015/16: Nuclear hormone receptors.

Stephen Ph Alexander1, John A Cidlowski2, Eamonn Kelly3, Neil Marrion3, John A Peters4, Helen E Benson5, Elena Faccenda5, Adam J Pawson5, Joanna L Sharman5, Christopher Southan5, Jamie A Davies5.   

Abstract

The Concise Guide to PHARMACOLOGY 2015/16 provides concise overviews of the key properties of over 1750 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13352/full. Nuclear hormone receptors are one of the eight major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, ligand-gated ion channels, voltage-gated ion channels, other ion channels, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The Concise Guide is published in landscape format in order to facilitate comparison of related targets. It is a condensed version of material contemporary to late 2015, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presented in the previous Guides to Receptors & Channels and the Concise Guide to PHARMACOLOGY 2013/14. It is produced in conjunction with NC-IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR-DB and GRAC and provides a permanent, citable, point-in-time record that will survive database updates.
© 2015 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society.

Entities:  

Mesh：

Substances：

Year:  2015        PMID： 26650443      PMCID： PMC4718213          DOI： 10.1111/bph.13352

Source DB:  PubMed          Journal:  Br J Pharmacol        ISSN： 0007-1188            Impact factor:   8.739


Conflict of interest

The authors state that there are no conflicts of interest to declare.

Overview

Nuclear hormone receptors are specialised transcription factors with commonalities of sequence and structure, which bind as homo‐ or heterodimers to specific consensus sequences of DNA (response elements) in the promoter region of particular target genes. They regulate (either promoting or repressing) transcription of these target genes in response to a variety of endogenous ligands. Endogenous agonists are hydrophobic entities which, when bound to the receptor promote conformational changes in the receptor to allow recruitment (or dissociation) of protein partners, generating a large multiprotein complex. Two major subclasses of nuclear receptors with identified endogenous agonists can be identified: steroid and non‐steroid hormone receptors. Steroid hormone receptors function typically as dimeric entities and are thought to be resident outside the nucleus in the unliganded state in a complex with chaperone proteins, which are liberated upon agonist binding. Migration to the nucleus and interaction with other regulators of gene transcription, including RNA polymerase, acetyltransferases and deacetylases, allows gene transcription to be regulated. Non‐steroid hormone receptors typically exhibit a greater distribution in the nucleus in the unliganded state and interact with other nuclear receptors to form heterodimers, as well as with other regulators of gene transcription, leading to changes in gene transcription upon agonist binding. Selectivity of gene regulation is brought about through interaction of nuclear receptors with particular consensus sequences of DNA, which are arranged typically as repeats or inverted palindromes to allow accumulation of multiple transcription factors in the promoter regions of genes.

Family structure

5958 1A. Thyroid hormone receptors 5959 1B. Retinoic acid receptors 5960 1C. Peroxisome proliferator‐activated receptors 5961 1D. Rev‐Erb receptors 5962 1F. Retinoic acid‐related orphans 5963 1H. Liver X receptor‐like receptors 5964 1I. Vitamin D receptor‐like receptors 5965 2A. Hepatocyte nuclear factor‐4 receptors 5966 2B. Retinoid X receptors 5967 2C. Testicular receptors 5968 2E. Tailless‐like receptors 5969 2F. COUP‐TF‐like receptors 5970 3B. Estrogen‐related receptors 5971 4A. Nerve growth factor IB‐like receptors 5972 5A. Fushi tarazu F1‐like receptors 5973 6A. Germ cell nuclear factor receptors 5974 0B. DAX‐like receptors 5975 Steroid hormone receptors 5975 3A. Estrogen receptors 5976 3C. 3‐Ketosteroid receptors

1A. Thyroid hormone receptors

Overview

Thyroid hormone receptors (TRs, nomenclature as agreed by the Subcommittee on Nuclear Hormone Receptors []) are nuclear hormone receptors of the NR1A family, with diverse roles regulating macronutrient metabolism, cognition and cardiovascular homeostasis. TRs are activated by thyroxine (T) and thyroid hormone (triiodothyronine). Once activated by a ligand, the receptor acts as a transcription factor either as a monomer, homodimer or heterodimer with members of the retinoid X receptor family. NH‐3 has been described as an antagonist at TRs with modest selectivity for TRβ[111].

Comments

An interaction with integrin αVβ3 has been suggested to underlie plasma membrane localization of TRs and non‐genomic signalling [9].One splice variant, TRα2, lacks a functional DNA‐binding domain and appears to act as a transcription suppressor. Although radioligand binding assays have been described for these receptors, the radioligands are not commercially available.

Further Reading

Bianco AC. (2011) Minireview: cracking the metabolic code for thyroid hormone signaling. Endocrinology 152: 3306‐11 [PMID:21712363] Brent GA. (2012) Mechanisms of thyroid hormone action. J. Clin. Invest. 122: 3035‐43 [PMID:22945636] Flamant F et al. (2006) International Union of Pharmacology. LIX. The pharmacology and classification of the nuclear receptor superfamily: thyroid hormone receptors. Pharmacol. Rev. 58: 705‐11 [PMID:17132849] Pramfalk C et al. (2011) Role of thyroid receptor β in lipid metabolism. Biochim. Biophys. Acta 1812: 929‐37 [PMID:21194564] Sirakov M et al. (2011) The thyroid hormones and their nuclear receptors in the gut: from developmental biology to cancer. Biochim. Biophys. Acta 1812: 938‐46 [PMID:21194566] Tancevski I et al. (2011) Thyromimetics: a journey from bench to bed‐side. Pharmacol. Ther. 131: 33‐9 [PMID:21504761]

1B. Retinoic acid receptors

Retinoic acid receptors (nomenclature as agreed by the Subcommittee on Nuclear Hormone Receptors []) are nuclear hormone receptors of the NR1B family activated by the vitamin A‐derived agonists tretinoin (ATRA) and alitretinoin, and the RAR‐selective synthetic agonists TTNPB and adapalene. BMS493 is a family‐selective antagonist [47]. Ro 41‐5253 has been suggested to be a PPARγ agonist [131]. LE135 is an antagonist with selectivity for RARα and RARβ compared with RARγ[85]. Bour G et al. (2007) Protein kinases and the proteasome join in the combinatorial control of transcription by nuclear retinoic acid receptors. Trends Cell Biol. 17: 302‐9 [PMID:17467991] Duong V et al. (2011) The molecular physiology of nuclear retinoic acid receptors. From health to disease. Biochim. Biophys. Acta 1812: 1023‐31 [PMID:20970498] Germain P et al. (2006) International Union of Pharmacology. LX. Retinoic acid receptors. Pharmacol. Rev. 58: 712‐25 [PMID:17132850] Maden M. (2007) Retinoic acid in the development, regeneration and maintenance of the nervous system. Nat. Rev. Neurosci. 8: 755‐65 [PMID:17882253] Mark M et al. (2006) Function of retinoid nuclear receptors: lessons from genetic and pharmacological dissections of the retinoic acid signaling pathway during mouse embryogenesis. Annu. Rev. Pharmacol. Toxicol. 46: 451‐80 [PMID:16402912]

1C. Peroxisome proliferator‐activated receptors

Peroxisome proliferator‐activated receptors (PPARs, nomenclature as agreed by the Subcommittee on Nuclear Hormone Receptors[]) are nuclear hormone receptors of the NR1C family, with diverse roles regulating lipid homeostasis, cellular differentiation, proliferation and the immune response. PPARs have many potential endogenous agonists [14, 101], including 15‐deoxy‐, prostacyclin (PGI), many fatty acids and their oxidation products, lysophosphatidic acid (LPA) [98], 13‐HODE, 15S‐HETE, Paz‐PC, azelaoyl‐PAF and leukotriene B4 (LTB). Bezafibrate acts as a non‐selective agonist for the PPAR family [159]. These receptors also bind hypolipidaemic drugs (PPARα) and anti‐diabetic thiazolidinediones (PPARγ), as well as many non‐steroidal anti‐inflammatory drugs, such as sulindac and indomethacin. Once activated by a ligand, the receptor forms a heterodimer with members of the retinoid X receptor family and can act as a transcription factor. Although radioligand binding assays have been described for all three receptors, the radioligands are not commercially available. Commonly, receptor occupancy studies are conducted using fluorescent ligands and truncated forms of the receptor limited to the ligand binding domain. As with the estrogen receptor antagonists, many agents show tissue‐selective efficacy (e.g. [13, 110, 125]). Agonists with mixed activity at PPARα and PPARγ have also been described (e.g [35, 52, 163]). Huang JV et al. (2012) PPAR‐γ as a therapeutic target in cardiovascular disease: evidence and uncertainty. J. Lipid Res. 53: 1738‐54 [PMID:22685322] Michalik L et al. (2006) International Union of Pharmacology. LXI. Peroxisome proliferator‐activated receptors. Pharmacol. Rev. 58: 726‐41 [PMID:17132851] Michalik L et al. (2008) PPARs Mediate Lipid Signaling in Inflammation and Cancer. PPAR Res 2008: 134059 [PMID:19125181] Peters JM et al. (2012) The role of peroxisome proliferator‐activated receptors in carcinogenesis and chemoprevention. Nat. Rev. Cancer 12: 181‐95 [PMID:22318237] Pirat C et al. (2012) Targeting peroxisome proliferator‐activated receptors (PPARs): development of modulators. J. Med. Chem. 55: 4027‐61 [PMID:22260081] Varga T et al. (2011) PPARs are a unique set of fatty acid regulated transcription factors controlling both lipid metabolism and inflammation. Biochim. Biophys. Acta 1812: 1007‐22 [PMID:21382489] Youssef J et al. (2011) Peroxisome proliferator‐activated receptors and cancer: challenges and opportunities. Br. J. Pharmacol. 164: 68‐82 [PMID:21449912]

1D. Rev‐Erb receptors

Rev‐erb receptors (nomenclature as agreed by the Subcommittee on Nuclear Hormone Receptors []) have yet to be officially paired with an endogenous ligand, but are thought to be activated by heme. Benoit G et al. (2006) International Union of Pharmacology. LXVI. Orphan nuclear receptors. Pharmacol. Rev. 58: 798‐836 [PMID:17132856] Duez H et al. (2009) Rev‐erb‐alpha: an integrator of circadian rhythms and metabolism. J. Appl. Physiol. 107: 1972‐80 [PMID:19696364] Germain P et al. (2006) Overview of nomenclature of nuclear receptors. Pharmacol. Rev. 58: 685‐704 [PMID:17132848] Huang P et al. (2010) Structural overview of the nuclear receptor superfamily: insights into physiology and therapeutics. Annu. Rev. Physiol. 72: 247‐72 [PMID:20148675] Phelan CA et al. (2010) Structure of Rev‐erbalpha bound to N‐CoR reveals a unique mechanism of nuclear receptor‐co‐repressor interaction. Nat. Struct. Mol. Biol. 17: 808‐14 [PMID:20581824] Sladek FM. (2011) What are nuclear receptor ligands? Mol. Cell. Endocrinol. 334: 3‐13 [PMID:20615454] Yin L et al. (2010) Nuclear receptor Rev‐erbalpha: a heme receptor that coordinates circadian rhythm and metabolism. Nucl Recept Signal 8: e001 [PMID:20414452]

1F. Retinoic acid‐related orphans

Retinoic acid receptor‐related orphan receptors (ROR, nomenclature as agreed by the Subcommittee on Nuclear Hormone Receptors []) have yet to be assigned a definitive endogenous ligand, although RORα may be synthesized with a ‘captured’ agonist such as cholesterol[66, 67]. tretinoin shows selectivity for RORβ within the ROR family [139]. RORα has been suggested to be a nuclear receptor responding to melatonin[158]. Benoit G et al. (2006) International Union of Pharmacology. LXVI. Orphan nuclear receptors. Pharmacol. Rev. 58: 798‐836 [PMID:17132856]

1H. Liver X receptor‐like receptors

Liver X and farnesoid X receptors (LXR and FXR, nomenclature as agreed by the Subcommittee on Nuclear Hormone Receptors[]) are members of a steroid analogue‐activated nuclear receptor subfamily, which form heterodimers with members of the retinoid X receptor family. Endogenous ligands for LXRs include hydroxycholesterols (OHC), while FXRs appear to be activated by bile acids. T0901317[123] and GW3965[28] are synthetic agonists acting at both LXRα and LXRβ with less than 10‐fold selectivity. A‐González N et al. (2011) Liver X receptors as regulators of macrophage inflammatory and metabolic pathways. Biochim. Biophys. Acta 1812: 982‐94 [PMID:21193033] Calkin AC et al. (2010) Liver x receptor signaling pathways and atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 30: 1513‐8 [PMID:20631351] Chen WD et al. (2011) Nuclear bile acid receptor FXR in the hepatic regeneration. Biochim. Biophys. Acta 1812: 888‐92 [PMID:21167938] Claudel T et al. (2011) Role of nuclear receptors for bile acid metabolism, bile secretion, cholestasis, and gallstone disease. Biochim. Biophys. Acta 1812: 867‐78 [PMID:21194565] El‐Hajjaji FZ et al. (2011) Liver X receptors, lipids and their reproductive secrets in the male. Biochim. Biophys. Acta 1812: 974‐81 [PMID:21334438] Gadaleta RM et al. (2010) Bile acids and their nuclear receptor FXR: Relevance for hepatobiliary and gastrointestinal disease. Biochim. Biophys. Acta 1801: 683‐92 [PMID:20399894] Gardmo C et al. (2011) Proteomics for the discovery of nuclear bile acid receptor FXR targets. Biochim. Biophys. Acta 1812: 836‐41 [PMID:21439373] Kemper JK. (2011) Regulation of FXR transcriptional activity in health and disease: Emerging roles of FXR cofactors and post‐translational modifications. Biochim. Biophys. Acta 1812: 842‐50 [PMID:21130162] Matsubara T et al. (2013) FXR signaling in the enterohepatic system. Mol. Cell. Endocrinol. 368: 17‐29 [PMID:22609541] Moore DD et al. (2006) International Union of Pharmacology. LXII. The NR1H and NR1I receptors: constitutive androstane receptor, pregnene X receptor, farnesoid X receptor alpha, farnesoid X receptor beta, liver X receptor alpha, liver X receptor beta, and vitamin D receptor. Pharmacol. Rev. 58: 742‐59 [PMID:17132852]

1I. Vitamin D receptor‐like receptors

Vitamin D (VDR), Pregnane X (PXR) and Constitutive Androstane (CAR) receptors (nomenclature as agreed by the Subcommittee on Nuclear Hormone Receptors[]) are members of the NR1I family of nuclear receptors, which form heterodimers with members of the retinoid X receptor family. PXR and CAR are activated by a range of exogenous compounds, with no established endogenous physiological agonists, although high concentrations of bile acids and bile pigments activate PXR and CAR [105]. Bikle DD. (2011) Vitamin D: an ancient hormone. Exp. Dermatol. 20: 7‐13 [PMID:21197695] Campbell FC et al. (2010) The yin and yang of vitamin D receptor (VDR) signaling in neoplastic progression: operational networks and tissue‐specific growth control. Biochem. Pharmacol. 79: 1‐9 [PMID:19737544] Chen Y et al. (2012) Nuclear receptors in the multidrug resistance through the regulation of drug‐metabolizing enzymes and drug transporters. Biochem. Pharmacol. 83: 1112‐26 [PMID:22326308] Cheng J et al. (2012) Pregnane X receptor as a target for treatment of inflammatory bowel disorders. Trends Pharmacol. Sci. 33: 323‐30 [PMID:22609277] Ihunnah CA et al. (2011) Nuclear receptor PXR, transcriptional circuits and metabolic relevance. Biochim. Biophys. Acta 1812: 956‐63 [PMID:21295138] Kachaylo EM et al. (2011) Constitutive androstane receptor (CAR) is a xenosensor and target for therapy. Biochemistry Mosc. 76: 1087‐97 [PMID:22098234] Moore DD et al. (2006) International Union of Pharmacology. LXII. The NR1H and NR1I receptors: constitutive androstane receptor, pregnene X receptor, farnesoid X receptor alpha, farnesoid X receptor beta, liver X receptor alpha, liver X receptor beta, and vitamin D receptor. Pharmacol. Rev. 58: 742‐59 [PMID:17132852] Plum LA et al. (2010) Vitamin D, disease and therapeutic opportunities. Nat Rev Drug Discov 9: 941‐55 [PMID:21119732] Staudinger JL et al. (2013) Nuclear‐receptor‐mediated regulation of drug‐ and bile‐acid‐transporter proteins in gut and liver. Drug Metab. Rev. 45: 48‐59 [PMID:23330541]

2A. Hepatocyte nuclear factor‐4 receptors

The nomenclature of hepatocyte nuclear factor‐4 receptors is agreed by the Subcommittee on Nuclear Hormone Receptors []. While linoleic acid has been identified as the endogenous ligand for HNF4α its function remains ambiguous [167]. HNF4γ has yet to be paired with an endogenous ligand. Benoit G et al. (2006) International Union of Pharmacology. LXVI. Orphan nuclear receptors. Pharmacol. Rev. 58: 798‐836 [PMID:17132856] Germain P et al. (2006) Overview of nomenclature of nuclear receptors. Pharmacol. Rev. 58: 685‐704 [PMID:17132848] Huang P et al. (2010) Structural overview of the nuclear receptor superfamily: insights into physiology and therapeutics. Annu. Rev. Physiol. 72: 247‐72 [PMID:20148675] Hwang‐Verslues WW et al. (2010) HNF4α–role in drug metabolism and potential drug target? Curr Opin Pharmacol 10: 698‐705 [PMID:20833107] Sladek FM. (2011) What are nuclear receptor ligands? Mol. Cell. Endocrinol. 334: 3‐13 [PMID:20615454]

2B. Retinoid X receptors

Retinoid X receptors (nomenclature as agreed by the Subcommittee on Nuclear Hormone Receptors []) are NR2B family members activated by alitretinoin and the RXR‐selective agonists bexarotene and LG100268, sometimes referred to as rexinoids. UVI3003[109] and HX 531 [37] have been described as a pan‐RXR antagonists. These receptors form RXR‐RAR heterodimers and RXR‐RXR homodimers [23, 97]. Bour G et al. (2007) Protein kinases and the proteasome join in the combinatorial control of transcription by nuclear retinoic acid receptors. Trends Cell Biol. 17: 302‐9 [PMID:17467991] Duong V et al. (2011) The molecular physiology of nuclear retinoic acid receptors. From health to disease. Biochim. Biophys. Acta 1812: 1023‐31 [PMID:20970498] Germain P et al. (2006) International Union of Pharmacology. LXIII. Retinoid X receptors. Pharmacol. Rev. 58: 760‐72 [PMID:17132853] Lefebvre P et al. (2010) Retinoid X receptors: common heterodimerization partners with distinct functions. Trends Endocrinol. Metab. 21: 676‐83 [PMID:20674387] Maden M. (2007) Retinoic acid in the development, regeneration and maintenance of the nervous system. Nat. Rev. Neurosci. 8: 755‐65 [PMID:17882253] Mark M et al. (2006) Function of retinoid nuclear receptors: lessons from genetic and pharmacological dissections of the retinoic acid signaling pathway during mouse embryogenesis. Annu. Rev. Pharmacol. Toxicol. 46: 451‐80 [PMID:16402912] Pérez E et al. (2011) Modulation of RXR function through ligand design. Biochim Biophys Acta [PMID:21515403]

2C. Testicular receptors

Testicular receptors (nomenclature as agreed by the Subcommittee on Nuclear Hormone Receptors []) have yet to be officially paired with an endogenous ligand, although testicular receptor 4 has been reported to respond to retinoids. Benoit G et al. (2006) International Union of Pharmacology. LXVI. Orphan nuclear receptors. Pharmacol. Rev. 58: 798‐836 [PMID:17132856] Duez H et al. (2009) Rev‐erb‐alpha: an integrator of circadian rhythms and metabolism. J. Appl. Physiol. 107: 1972‐80 [PMID:19696364] Germain P et al. (2006) Overview of nomenclature of nuclear receptors. Pharmacol. Rev. 58: 685‐704 [PMID:17132848] Huang P et al. (2010) Structural overview of the nuclear receptor superfamily: insights into physiology and therapeutics. Annu. Rev. Physiol. 72: 247‐72 [PMID:20148675] Phelan CA et al. (2010) Structure of Rev‐erbalpha bound to N‐CoR reveals a unique mechanism of nuclear receptor‐co‐repressor interaction. Nat. Struct. Mol. Biol. 17: 808‐14 [PMID:20581824] Schimmer BP et al. (2010) Minireview: steroidogenic factor 1: its roles in differentiation, development, and disease. Mol. Endocrinol. 24: 1322‐37 [PMID:20203099] Sladek FM. (2011) What are nuclear receptor ligands? Mol. Cell. Endocrinol. 334: 3‐13 [PMID:20615454] Yin L et al. (2010) Nuclear receptor Rev‐erbalpha: a heme receptor that coordinates circadian rhythm and metabolism. Nucl Recept Signal 8: e001 [PMID:20414452] Zhang Y et al. (2011) Role of nuclear receptor SHP in metabolism and cancer. Biochim. Biophys. Acta 1812: 893‐908 [PMID:20970497] Zhao Y et al. (2010) NR4A orphan nuclear receptors: transcriptional regulators of gene expression in metabolism and vascular biology. Arterioscler. Thromb. Vasc. Biol. 30: 1535‐41 [PMID:20631354]

2E. Tailless‐like receptors

Tailless‐like receptors (nomenclature as agreed by the Subcommittee on Nuclear Hormone Receptors []) have yet to be officially paired with an endogenous ligand. Benoit G et al. (2006) International Union of Pharmacology. LXVI. Orphan nuclear receptors. Pharmacol. Rev. 58: 798‐836 [PMID:17132856] Germain P et al. (2006) Overview of nomenclature of nuclear receptors. Pharmacol. Rev. 58: 685‐704 [PMID:17132848] Gui H et al. (2011) A tale of tailless. Dev. Neurosci. 33: 1‐13 [PMID:21124006] Huang P et al. (2010) Structural overview of the nuclear receptor superfamily: insights into physiology and therapeutics. Annu. Rev. Physiol. 72: 247‐72 [PMID:20148675] Sladek FM. (2011) What are nuclear receptor ligands? Mol. Cell. Endocrinol. 334: 3‐13 [PMID:20615454]

2F. COUP‐TF‐like receptors

COUP‐TF‐like receptors (nomenclature as agreed by the Subcommittee on Nuclear Hormone Receptors []) have yet to be officially paired with an endogenous ligand. Benoit G et al. (2006) International Union of Pharmacology. LXVI. Orphan nuclear receptors. Pharmacol. Rev. 58: 798‐836 [PMID:17132856] Germain P et al. (2006) Overview of nomenclature of nuclear receptors. Pharmacol. Rev. 58: 685‐704 [PMID:17132848] Huang P et al. (2010) Structural overview of the nuclear receptor superfamily: insights into physiology and therapeutics. Annu. Rev. Physiol. 72: 247‐72 [PMID:20148675] Lin FJ et al. (2011) Coup d'Etat: an orphan takes control. Endocr. Rev. 32: 404‐21 [PMID:21257780] Sladek FM. (2011) What are nuclear receptor ligands? Mol. Cell. Endocrinol. 334: 3‐13 [PMID:20615454]

3B. Estrogen‐related receptors

Estrogen‐related receptors (nomenclature as agreed by the Subcommittee on Nuclear Hormone Receptors []) have yet to be officially paired with an endogenous ligand. Benoit G et al. (2006) International Union of Pharmacology. LXVI. Orphan nuclear receptors. Pharmacol. Rev. 58: 798‐836 [PMID:17132856] Deblois G et al. (2011) Functional and physiological genomics of estrogen‐related receptors (ERRs) in health and disease. Biochim. Biophys. Acta 1812: 1032‐40 [PMID:21172432] Deblois G et al. (2013) Oestrogen‐related receptors in breast cancer: control of cellular metabolism and beyond. Nat. Rev. Cancer 13: 27‐36 [PMID:23192231] Germain P et al. (2006) Overview of nomenclature of nuclear receptors. Pharmacol. Rev. 58: 685‐704 [PMID:17132848] Huang P et al. (2010) Structural overview of the nuclear receptor superfamily: insights into physiology and therapeutics. Annu. Rev. Physiol. 72: 247‐72 [PMID:20148675] Hwang‐Verslues WW et al. (2010) HNF4α–role in drug metabolism and potential drug target? Curr Opin Pharmacol 10: 698‐705 [PMID:20833107] Sladek FM. (2011) What are nuclear receptor ligands? Mol. Cell. Endocrinol. 334: 3‐13 [PMID:20615454]

4A. Nerve growth factor IB‐like receptors

Nerve growth factor IB‐like receptors (nomenclature as agreed by the Subcommittee on Nuclear Hormone Receptors []) have yet to be officially paired with an endogenous ligand. Benoit G et al. (2006) International Union of Pharmacology. LXVI. Orphan nuclear receptors. Pharmacol. Rev. 58: 798‐836 [PMID:17132856] Germain P et al. (2006) Overview of nomenclature of nuclear receptors. Pharmacol. Rev. 58: 685‐704 [PMID:17132848] Huang P et al. (2010) Structural overview of the nuclear receptor superfamily: insights into physiology and therapeutics. Annu. Rev. Physiol. 72: 247‐72 [PMID:20148675] McMorrow JP et al. (2011) Inflammation: a role for NR4A orphan nuclear receptors? Biochem. Soc. Trans. 39: 688‐93 [PMID:21428963] Mohan HM et al. (2012) Molecular pathways: the role of NR4A orphan nuclear receptors in cancer. Clin. Cancer Res. 18: 3223‐8 [PMID:22566377] Pearen MA et al. (2010) Minireview: Nuclear hormone receptor 4A signaling: implications for metabolic disease. Mol. Endocrinol. 24: 1891‐903 [PMID:20392876] Sladek FM. (2011) What are nuclear receptor ligands? Mol. Cell. Endocrinol. 334: 3‐13 [PMID:20615454] Zhao Y et al. (2010) NR4A orphan nuclear receptors: transcriptional regulators of gene expression in metabolism and vascular biology. Arterioscler. Thromb. Vasc. Biol. 30: 1535‐41 [PMID:20631354] van Tiel CM et al. (2012) NR4All in the vessel wall. J. Steroid Biochem. Mol. Biol. 130: 186‐93 [PMID:21277978]

5A. Fushi tarazu F1‐like receptors

Fushi tarazu F1‐like receptors (nomenclature as agreed by the Subcommittee on Nuclear Hormone Receptors []) have yet to be officially paired with an endogenous ligand. Benoit G et al. (2006) International Union of Pharmacology. LXVI. Orphan nuclear receptors. Pharmacol. Rev. 58: 798‐836 [PMID:17132856] Büdefeld T et al. (2012) Steroidogenic factor 1 and the central nervous system. J. Neuroendocrinol. 24: 225‐35 [PMID:21668533] El‐Khairi R et al. (2011) Role of DAX‐1 (NR0B1) and steroidogenic factor‐1 (NR5A1) in human adrenal function. Endocr Dev 20: 38‐46 [PMID:21164257] Fernandez‐Marcos PJ et al. (2011) Emerging actions of the nuclear receptor LRH‐1 in the gut. Biochim. Biophys. Acta 1812: 947‐55 [PMID:21194563] Ferraz‐de‐Souza B et al. (2011) Steroidogenic factor‐1 (SF‐1, NR5A1) and human disease. Mol. Cell. Endocrinol. 336: 198‐205 [PMID:21078366] Germain P et al. (2006) Overview of nomenclature of nuclear receptors. Pharmacol. Rev. 58: 685‐704 [PMID:17132848] Huang P et al. (2010) Structural overview of the nuclear receptor superfamily: insights into physiology and therapeutics. Annu. Rev. Physiol. 72: 247‐72 [PMID:20148675] Lazarus KA et al. (2012) Therapeutic potential of Liver Receptor Homolog‐1 modulators. J. Steroid Biochem. Mol. Biol. 130: 138‐46 [PMID:22266285] Mlnynarczuk J et al. (2010) The role of the orphan receptor SF‐1 in the development and function of the ovary. Reprod Biol 10: 177‐93 [PMID:21113200] Schimmer BP et al. (2010) Minireview: steroidogenic factor 1: its roles in differentiation, development, and disease. Mol. Endocrinol. 24: 1322‐37 [PMID:20203099] Sladek FM. (2011) What are nuclear receptor ligands? Mol. Cell. Endocrinol. 334: 3‐13 [PMID:20615454]

6A. Germ cell nuclear factor receptors

Germ cell nuclear factor receptors (nomenclature as agreed by the Subcommittee on Nuclear Hormone Receptors []) have yet to be officially paired with an endogenous ligand. Benoit G et al. (2006) International Union of Pharmacology. LXVI. Orphan nuclear receptors. Pharmacol. Rev. 58: 798‐836 [PMID:17132856] Germain P et al. (2006) Overview of nomenclature of nuclear receptors. Pharmacol. Rev. 58: 685‐704 [PMID:17132848] Huang P et al. (2010) Structural overview of the nuclear receptor superfamily: insights into physiology and therapeutics. Annu. Rev. Physiol. 72: 247‐72 [PMID:20148675] Sladek FM. (2011) What are nuclear receptor ligands? Mol. Cell. Endocrinol. 334: 3‐13 [PMID:20615454]

0B. DAX‐like receptors

Dax‐like receptors (nomenclature as agreed by the Subcommittee on Nuclear Hormone Receptors []) have yet to be officially paired with an endogenous ligand. Benoit G et al. (2006) International Union of Pharmacology. LXVI. Orphan nuclear receptors. Pharmacol. Rev. 58: 798‐836 [PMID:17132856] Chanda D et al. (2008) Molecular basis of endocrine regulation by orphan nuclear receptor Small Heterodimer Partner. Endocr. J. 55: 253‐68 [PMID:17984569] Ehrlund A et al. (2012) Ligand‐independent actions of the orphan receptors/corepressors DAX‐1 and SHP in metabolism, reproduction and disease. J. Steroid Biochem. Mol. Biol. 130: 169‐79 [PMID:21550402] El‐Khairi R et al. (2011) Role of DAX‐1 (NR0B1) and steroidogenic factor‐1 (NR5A1) in human adrenal function. Endocr Dev 20: 38‐46 [PMID:21164257] Germain P et al. (2006) Overview of nomenclature of nuclear receptors. Pharmacol. Rev. 58: 685‐704 [PMID:17132848] Huang P et al. (2010) Structural overview of the nuclear receptor superfamily: insights into physiology and therapeutics. Annu. Rev. Physiol. 72: 247‐72 [PMID:20148675] Mlnynarczuk J et al. (2010) The role of the orphan receptor SF‐1 in the development and function of the ovary. Reprod Biol 10: 177‐93 [PMID:21113200] Sladek FM. (2011) What are nuclear receptor ligands? Mol. Cell. Endocrinol. 334: 3‐13 [PMID:20615454] Zhang Y et al. (2011) Role of nuclear receptor SHP in metabolism and cancer. Biochim. Biophys. Acta 1812: 893‐908 [PMID:20970497]

Steroid hormone receptors

Steroid hormone receptors (nomenclature as agreed by the Subcommittee on Nuclear Hormone Receptors [, ]) are nuclear hormone receptors of the NR3 class, with endogenous agonists that may be divided into 3‐hydroxysteroids (estrone and 17β‐estradiol) and 3‐ketosteroids (dihydrotestosterone[DHT], aldosterone, cortisol, corticosterone, progesterone and testosterone). These receptors exist as dimers coupled with chaperone molecules (such as hsp90β(, P08238) and immunophilin FKBP52:, Q02790), which are shed on binding the steroid hormone. Although rapid signalling phenomena are observed [84, 120], the principal signalling cascade appears to involve binding of the activated receptors to nuclear hormone response elements of the genome, with a 15‐nucleotide consensus sequence AGAACAnnnTGTTCT (i.e. an inverted palindrome) as homo‐ or heterodimers. They also affect transcription by protein‐protein interactions with other transcription factors, such as activator protein 1 (AP‐1) and nuclear factor κB (NF‐κB). Splice variants of each of these receptors can form functional or non‐functional monomers that can dimerize to form functional or non‐functional receptors. For example, alternative splicing of PR mRNA produces A and B monomers that combine to produce functional AA, AB and BB receptors with distinct characteristics [150]. A 7TM receptor responsive to estrogen (, Q99527, also known as GPR30, see [119]) has been described. Human orthologues of 7TM 'membrane progestin receptors' (, and ), initially discovered in fish [174, 175], appear to localize to intracellular membranes and respond to 'non‐genomic' progesterone analogues independently of G proteins [137].

3A. Estrogen receptors

Estrogen receptor (ER) activity regulates diverse physiological processes via transcriptional modulation of target genes. The selection of target genes and the magnitude of the response, be it induction or repression, are determined by many factors, including the effect of the hormone ligand and DNA binding on ER structural conformation, and the local cellular regulatory environment. The cellular environment defines the specific complement of DNA enhancer and promoter elements present and the availability of coregulators to form functional transcription complexes. Together, these determinants control the resulting biological response. R,R‐THC exhibits partial agonist activity at ERα[99, 143]. Estrogen receptors may be blocked non‐selectively by tamoxifen and raloxifene and labelled by [ and [. Many agents thought initially to be antagonists at estrogen receptors appear to have tissue‐specific efficacy (e.g. Tamoxifen is an antagonist at estrogen receptors in the breast, but is an agonist at estrogen receptors in the uterus), hence the descriptor SERM (selective estrogen receptor modulator) or SnuRM (selective nuclear receptor modulator). Y134 has been suggested to be an ERα‐selective estrogen receptor modulator [112].

3C. 3‐Ketosteroid receptors

[ also binds to MRin vitro. PR antagonists have been suggested to subdivide into Type I (e.g. onapristone) and Type II (e.g. ZK112993) groups. These groups appear to promote binding of PR to DNA with different efficacies and evoke distinct conformational changes in the receptor, leading to a transcription‐neutral complex [43, 83]. Mutations in AR underlie testicular feminization and androgen insensibility syndromes, spinal and bulbar muscular atrophy (Kennedy's disease).
Nomenclature Thyroid hormone receptor‐α Thyroid hormone receptor‐β
Systematic nomenclatureNR1A1NR1A2
HGNC, UniProt THRA, P10827 THRB, P10828
Rank order of potency triiodothyronine>T4 triiodothyronine>T4
Agonists dextrothyroxine [20] dextrothyroxine [20]
Selective agonists– sobetirome (pK d 10.2) [27, 133]
Nomenclature Retinoic acid receptor‐α Retinoic acid receptor‐β Retinoic acid receptor‐γ
Systematic nomenclatureNR1B1NR1B2NR1B3
HGNC, UniProt RARA, P10276 RARB, P10826 RARG, P13631
Agonists tretinoin (pEC50 7.8) [26] tretinoin (pEC50 7.9) [26] tretinoin (pEC50 9.7) [26]
(Sub)family‐selective agonists tazarotene (pEC50 7.2) [26] tazarotene (pEC50 9.1) [26], adapalene (pK i 7.5) [25] tazarotene (pEC50 7.4) [26], adapalene (pK i 6.9) [25]
Selective agonists BMS753 (pK i 8.7) [53], Ro 40‐6055 (pK d 8.2) [33], tamibarotene (pIC50 6.9) [65, 108, 146] AC261066 (pEC50 7.9–8.1) [90], AC55649 (pEC50 6.5–7.3) [90] AHPN (pK i 7.1) [25]
Selective antagonists Ro 41‐5253 (pIC50 6.3–7.2) [2, 70]– MM 11253 [77]
Nomenclature Peroxisome proliferator‐activated receptor‐α Peroxisome proliferator‐activated receptor‐β/δ Peroxisome proliferator‐activated receptor‐γ
Systematic nomenclatureNR1C1NR1C2NR1C3
HGNC, UniProt PPARA, Q07869 PPARD, Q03181 PPARG, P37231
Agonists–– mesalazine (pIC50 1.8) [126]
Selective agonists GW7647 (pEC50 8.2) [18, 19], CP‐775146 (pEC50 7.3) [68], pirinixic acid (pEC50 5.3) [159], gemfibrozil (pEC50 4.2) [31], ciprofibrate GW0742X (pIC50 9) [50, 144], GW501516 (pEC50 9) [113] GW1929 (pK i 8.8) [18], bardoxolone (Partial agonist) (pK i 8) [153], rosiglitazone (pK d 7.4) [59, 81, 165], rosiglitazone (pK i 6.9) [88], troglitazone (pIC50 6.3) [59, 165], pioglitazone (pIC50 6.2) [59, 129, 165], troglitazone (pK i 5.8) [8], ciglitazone (pEC50 4.6) [59]
Selective antagonists GW6471 (pIC50 6.6) [162] GSK0660 (pIC50 6.5) [134] T0070907 (pK i 9) [78], GW9662 (Irreversible inhibition) (pIC50 8.1) [79], CDDO‐Me (pK i 6.9) [153]
Nomenclature Rev‐Erb‐α Rev‐Erb‐β
Systematic nomenclatureNR1D1NR1D2
HGNC, UniProt NR1D1, P20393 NR1D2, Q14995
Endogenous agonists heme (Selective) [122, 164] heme (Selective) [122, 164]
Selective agonists GSK4112 (pEC50 6.4) [51], GSK4112 (pIC50 5.6) [73]–
Selective antagonists SR8278 (pIC50 6.5) [73]–
Nomenclature RAR‐related orphan receptor‐α RAR‐related orphan receptor‐β RAR‐related orphan receptor‐γ
Systematic nomenclatureNR1F1NR1F2NR1F3
HGNC, UniProt RORA, P35398 RORB, Q92753 RORC, P51449
Endogenous agonists cholesterol (Selective) [67, 115]––
Selective agonists 7‐hydroxycholesterol [15], cholesterol sulphate [15, 67]––
Nomenclature Farnesoid X receptor Farnesoid X receptor‐β Liver X receptor‐α Liver X receptor‐β
Systematic nomenclatureNR1H4NR1H5NR1H3NR1H2
HGNC, UniProt NR1H4, Q96RI1 NR1H5P, – NR1H3, Q13133 NR1H2, P55055
Potency order chenodeoxycholic acid>lithocholic acid, deoxycholic acid [93, 116]– 20S‐hydroxycholesterol, 22R‐hydroxycholesterol, 24(S)‐hydroxycholesterol>25‐hydroxycholesterol, 27‐hydroxycholesterol [80] 20S‐hydroxycholesterol, 22R‐hydroxycholesterol, 24(S)‐hydroxycholesterol>25‐hydroxycholesterol, 27‐hydroxycholesterol [80]
Endogenous agonists– lanosterol (pEC50 6) [114] – Mouse––
Selective agonists GW4064 (pEC50 7.8) [95], obeticholic acid (pEC50 7) [117], fexaramine (pEC50 6.6) [36]–––
Selective antagonists guggulsterone (pIC50 5.7–6) [161]–––
Nomenclature Vitamin D receptor Pregnane X receptor Constitutive androstane receptor
Systematic nomenclatureNR1I1NR1I2NR1I3
HGNC, UniProt VDR, P11473 NR1I2, O75469 NR1I3, Q14994
Endogenous agonists 1,25‐dihydroxyvitamin D3 (pK d 8.9–9.2) [12, 39] 17β‐estradiol (Selective) [64]–
Selective agonists seocalcitol (pK d 9.6) [29, 157], doxercalciferol hyperforin (pEC50 7.6) [106, 156], 5β‐pregnane‐3,20‐dione (pIC50 6.4) [64], lovastatin (pEC50 5.3–6) [82], rifampicin (pEC50 5.5–6) [16, 82] TCPOBOP (pEC50 7.7) [149] – Mouse, CITCO (pEC50 7.3) [92]
Selective antagonists TEI‐9647 (pIC50 8.2) [128] – Chicken, ZK159222 (pIC50 7.5) [42, 60]––
Comments–– clotrimazole [107] and T0901317 [69] although acting at other sites, function as antagonists of the constitutive androstane receptor.
Nomenclature Hepatocyte nuclear factor‐4‐α Hepatocyte nuclear factor‐4‐γ
Systematic nomenclatureNR2A1NR2A2
HGNC, UniProt HNF4A, P41235 HNF4G, Q14541
Endogenous agonists linoleic acid (Selective) [167]–
Selective antagonists BI6015 [72]–
CommentsHNF4α has constitutive transactivation activity [167] and binds DNA as a homodimer [63].–
Nomenclature Retinoid X receptor‐α Retinoid X receptor‐β Retinoid X receptor‐γ
Systematic nomenclatureNR2B1NR2B2NR2B3
HGNC, UniProt RXRA, P19793 RXRB, P28702 RXRG, P48443
(Sub)family‐selective agonists bexarotene (pIC50 7.4) [17, 22, 146] bexarotene (pIC50 7.7) [17, 22, 146] bexarotene (pIC50 7.5) [17, 22, 146]
Selective agonists CD3254 (pIC50 8.5) [48]––
Nomenclature Testicular receptor 2 Testicular receptor 4
Systematic nomenclatureNR2C1NR2C2
HGNC, UniProt NR2C1, P13056 NR2C2, P49116
Endogenous agonists– retinol (Selective) [173], tretinoin (Selective) [173]
CommentsForms a heterodimer with TR4; gene disruption appears without effect on testicular development or function [135].Forms a heterodimer with TR2.
Nomenclature TLX PNR
Systematic nomenclatureNR2E1NR2E3
HGNC, UniProt NR2E1, Q9Y466 NR2E3, Q9Y5X4
CommentsGene disruption is associated with abnormal brain development [76, 104].–
Nomenclature COUP‐TF1 COUP‐TF2 V‐erbA‐related gene
Systematic nomenclatureNR2F1NR2F2NR2F6
HGNC, UniProt NR2F1, P10589 NR2F2, P24468 NR2F6, P10588
CommentsGene disruption is perinatally lethal [121].Gene disruption is embryonically lethal [118].Gene disruption impairs CNS development [155].
Nomenclature Estrogen‐related receptor‐α Estrogen‐related receptor‐β Estrogen‐related receptor‐γ
Systematic nomenclatureNR3B1NR3B2NR3B3
HGNC, UniProt ESRRA, P11474 ESRRB, O95718 ESRRG, P62508
CommentsActivated by some dietary flavonoids [141]; activated by the syntheticagonist GSK4716 [176] and blocked by XCT790 [160].May be activated by DY131 [166].May be activated by DY131 [166].
Nomenclature Nerve Growth factor IB Nuclear receptor related 1 Neuron‐derived orphan receptor 1
Systematic nomenclatureNR4A1NR4A2NR4A3
HGNC, UniProt NR4A1, P22736 NR4A2, P43354 NR4A3, Q92570
CommentsAn endogenous agonist, cytosporone B, has been described [168], although structural analysis and molecular modelling has not identified a ligand binding site [4, 40, 154].––
Nomenclature Steroidogenic factor 1 Liver receptor homolog‐1
Systematic nomenclatureNR5A1NR5A2
HGNC, UniProt NR5A1, Q13285 NR5A2, O00482
CommentsReported to be inhibited by AC45594 [32] and SID7969543 [91].–
Nomenclature Germ cell nuclear factor
Systematic nomenclatureNR6A1
HGNC, UniProt NR6A1, Q15406
Nomenclature DAX1 SHP
Systematic nomenclatureNR0B1NR0B2
HGNC, UniProt NR0B1, P51843 NR0B2, Q15466
Nomenclature Estrogen receptor‐α Estrogen receptor‐β
Systematic nomenclatureNR3A1NR3A2
HGNC, UniProt ESR1, P03372 ESR2, Q92731
Endogenous agonists estriol (pK i 8.7) [75], estrone (pK i 8.5) [75]–
Selective agonists propylpyrazoletriol (pK i 9.6) [74, 138], ethinyl estradiol (pIC50 8.7) [62] WAY200070 (pIC50 8.5–9) [94], diarylpropionitril (pK i 8.6) [100, 138], prinaberel (pIC50 8.3) [94]
(Sub)family‐selective antagonists bazedoxifene (pIC50 7.6) [103] bazedoxifene (pIC50 7.1) [103]
Selective antagonists clomiphene (pK i 8.9) [[3]], methyl‐piperidino‐pyrazole (pK i 8.6) [142] R,R‐THC (pK i 8.4) [99, 143], PHTPP (pK i 6.9) [172]
Nomenclature Androgen receptor Glucocorticoid receptor Mineralocorticoid receptor Progesterone receptor
Systematic nomenclatureNR3C4NR3C1NR3C2NR3C3
HGNC, UniProt AR, P10275 NR3C1, P04150 NR3C2, P08235 PGR, P06401
Rank order of potency dihydrotestosterone>testosterone cortisol, corticosterone≫aldosterone, deoxycortisone [127] corticosterone, cortisol, aldosterone, progesterone [127] progesterone
Endogenous agonists dihydrotestosterone (pK d 9.3) [147]– aldosterone (Selective) (pIC50 9.8–10) [58, 127] progesterone (Selective) (pEC50 8.8) [38]
Agonists methyltestosterone (Androgen receptor promoter activity in luciferase reporter assay) (pEC50 9.7) [1], danazol (pK i 8) [24] – Rat, ethylestrenol, nandrolone –––
Selective agonists testosterone propionate (pK i 9.6) [96], mibolerone (pIC50 9) [49], fluoxymesterone (pK i 8.2) [61], methyltrienolone (pEC50<5) [152], dromostanolone propionate fluticasone propionate (pIC50 9.3) [11], clobetasol propionate (pK i 9.2) [[3]], desoximetasone (pK i 8.9) [[3]], fluorometholone (pK i 8.8) [[3]], flunisolide (pK i 8.6) [[3]], diflorasone diacetate (pK i 8.5) [[3]], fluocinolone acetonide (pIC50 8.5) [[3]], beclometasone (pK i 8.4) [[3]], methylprednisolone (pK i 8.3) [[3]], fluocinonide (pIC50 8.3) [[3]], betamethasone (pIC50 8.1) [[3]], budesonide (pEC50 7.9) [102], triamcinolone (pIC50 7.7) [87], ZK216348 (pIC50 7.7) [132], ciclesonide (pK i 7.4) [6], prednisone (pK i 6.3) [[3]], RU26988 – Unknown, RU28362, difluprednate [145], fluticasone – medroxyprogesterone (Affinity at human PR‐A) (pK i 9.5) [170], ORG2058, levonorgestrel [10, 130]
Antagonists cyproterone acetate (pK i 7.8) [55] mifepristone (pK d 9.4) [57, 127] nimodipine (inhibition of aldosterone‐induced luciferase activity in a reporter system driven by the mineralocorticoid receptor ligand binding domain) (pIC50 6.8) [34]–
Selective antagonists bicalutamide (pK i 7.7) [71], PF0998425 (pIC50 7.1–7.5) [86], enzalutamide (pIC50 7.4) [148], nilutamide (pIC50 7.1–7.1) [136], hydroxyflutamide (pEC50 6.6) [152], galeterone (pIC50 6.4) [56], flutamide (Displacement of 3[H] testosterone from wild‐type androgen receptors) (pK i 5.4) [151] onapristone (pIC50 7.6) [169], ZK112993 finerenone (pIC50 7.7) [21], eplerenone (pK i 6.9) [5], onapristone (pIC50 6.3) [169], RU28318, ZK112993 ulipristal acetate (pIC50 9.7) [124], mifepristone (Mixed) (pK i 9) [171], onapristone (pK i 7.7) [54], ZK112993
Labelled ligands [3H]dihydrotestosterone (Selective Agonist), [3H]methyltrienolone (Selective Agonist), [3H]mibolerone (Agonist) [3H]dexamethasone (Agonist) [3H]aldosterone (Selective Agonist) (pK d 9.5–9.4) [44, 140] – Rat [3H]ORG2058 (Selective Agonist)
  107 in total

1.  Metabolic profiling of murine plasma reveals eicosapentaenoic acid metabolites protecting against endothelial activation and atherosclerosis.

Authors:  Yajin Liu; Xuan Fang; Xu Zhang; Jing Huang; Jinlong He; Liyuan Peng; Chenji Ye; Yingmei Wang; Fengxia Xue; Ding Ai; Dan Li; Yi Zhu
Journal:  Br J Pharmacol       Date:  2017-09-05       Impact factor: 8.739

2.  Single administration of recombinant IL-6 restores the gene expression of lipogenic enzymes in liver of fasting IL-6-deficient mice.

Authors:  A L Gavito; R Cabello; J Suarez; A Serrano; F J Pavón; M Vida; M Romero; V Pardo; D Bautista; S Arrabal; J Decara; A L Cuesta; A M Valverde; F Rodríguez de Fonseca; E Baixeras
Journal:  Br J Pharmacol       Date:  2016-02-22       Impact factor: 8.739

Review 3.  Cannabidiol regulation of emotion and emotional memory processing: relevance for treating anxiety-related and substance abuse disorders.

Authors:  Jonathan L C Lee; Leandro J Bertoglio; Francisco S Guimarães; Carl W Stevenson
Journal:  Br J Pharmacol       Date:  2017-03-09       Impact factor: 8.739

Review 4.  Allosteric pathways in nuclear receptors - Potential targets for drug design.

Authors:  Elias J Fernandez
Journal:  Pharmacol Ther       Date:  2017-10-31       Impact factor: 12.310

Review 5.  Branched-chain amino acids differently modulate catabolic and anabolic states in mammals: a pharmacological point of view.

Authors:  Francesco Bifari; Enzo Nisoli
Journal:  Br J Pharmacol       Date:  2016-10-25       Impact factor: 8.739

Review 6.  Curcumin, the golden nutraceutical: multitargeting for multiple chronic diseases.

Authors:  Ajaikumar B Kunnumakkara; Devivasha Bordoloi; Ganesan Padmavathi; Javadi Monisha; Nand Kishor Roy; Sahdeo Prasad; Bharat B Aggarwal
Journal:  Br J Pharmacol       Date:  2016-10-21       Impact factor: 8.739

Review 7.  Carotenoids: biochemistry, pharmacology and treatment.

Authors:  Alireza Milani; Marzieh Basirnejad; Sepideh Shahbazi; Azam Bolhassani
Journal:  Br J Pharmacol       Date:  2016-10-29       Impact factor: 8.739

Review 8.  Protein S-sulfhydration by hydrogen sulfide in cardiovascular system.

Authors:  Guoliang Meng; Shuang Zhao; Liping Xie; Yi Han; Yong Ji
Journal:  Br J Pharmacol       Date:  2017-05-24       Impact factor: 8.739

Review 9.  Probiotics, fibre and herbal medicinal products for functional and inflammatory bowel disorders.

Authors:  Diego Currò; Gianluca Ianiro; Silvia Pecere; Stefano Bibbò; Giovanni Cammarota
Journal:  Br J Pharmacol       Date:  2016-10-25       Impact factor: 8.739

Review 10.  The therapeutic and diagnostic potential of the prostate specific membrane antigen/glutamate carboxypeptidase II (PSMA/GCPII) in cancer and neurological disease.

Authors:  James C Evans; Meenakshi Malhotra; John F Cryan; Caitriona M O'Driscoll
Journal:  Br J Pharmacol       Date:  2016-09-23       Impact factor: 8.739
View more

北京卡尤迪生物科技股份有限公司 © 2022-2023.