The pregnane X receptor (PXR, encoded by the NR1I2 gene) is a ligand-regulated transcription factor originally described as a master regulator of xenobiotic detoxification. Later, however, PXR was also shown to interact with endogenous metabolism and to be further associated with various pathological states. This review focuses predominantly on such aspects, currently less covered in literature, as the control of PXR expression per se in the context of inter-individual differences in drug metabolism. There is growing evidence that non-coding RNAs post-transcriptionally regulate PXR. Effects on PXR have especially been reported for microRNAs (miRNAs), which include miR-148a, miR-18a-5p, miR-140-3p, miR-30c-1-3p and miR-877-5p. Likewise, miRNAs control the expression of both transcription factors involved in PXR expression and regulators of PXR function. The impact of NR1I2 genetic polymorphisms on miRNA-mediated PXR regulation is also discussed. As revealed recently, long non-coding RNAs (lncRNAs) appear to interfere with PXR expression. Reciprocally, PXR activation regulates non-coding RNA expression, thus comprising another level of PXR action in addition to the direct transactivation of protein-coding genes. PXR expression is further controlled by several transcription factors (cross-regulation) giving rise to different PXR transcript variants. Controversies remain regarding the suggested role of feedback regulation (auto-regulation) of PXR expression. In this review, we comprehensively summarize the miRNA-mediated, lncRNA-mediated and transcriptional regulation of PXR expression, and we propose that deciphering the precise mechanisms of PXR expression may bridge our knowledge gap in inter-individual differences in drug metabolism and toxicity.

• Klíčová slova
• CYP3A4, Gene expression, Non-coding RNA, Post-transcriptional regulation, Pregnane X receptor, microRNA,
• MeSH
• biologická variabilita populace * MeSH
• biotransformace MeSH
• farmakogenetika MeSH
• farmakogenomické varianty * MeSH
• fenotyp MeSH
• genetická transkripce * MeSH
• genotyp MeSH
• lidé MeSH
• mikro RNA genetika   metabolismus   MeSH
• posttranskripční úpravy RNA * MeSH
• pregnanový X receptor genetika   metabolismus   MeSH
• RNA dlouhá nekódující genetika   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• mikro RNA MeSH
• NR1I2 protein, human MeSH Prohlížeč
• pregnanový X receptor MeSH
• RNA dlouhá nekódující MeSH

Pregnane X receptor (PXR) is the major regulator of xenobiotic metabolism. PXR itself is controlled by various signaling molecules including glucocorticoids. Moreover, negative feed-back regulation has been proposed at the transcriptional level. We examined the involvement of the 3'-untranslated region (3'-UTR) of NR1I2 mRNA and microRNAs in PXR- and glucocorticoid receptor (GR)-mediated regulation of NR1I2 gene expression. PXR ligands were found to significantly downregulate NR1I2 mRNA expression in a set of 14 human hepatocyte cultures. Similarly, PXR was downregulated by PCN in the C57/BL6 mice liver. In mechanistic studies with the full-length 3'-UTR cloned into luciferase reporter or expression vectors, we showed that the 3'-UTR reduces PXR expression. From the miRNAs tested, miR-18a-5p inhibited both NR1I2 expression and CYP3A4 gene induction. Importantly, we observed significant upregulation of miR-18a-5p expression 6 h after treatment with the PXR ligand rifampicin, which indicates a putative mechanism underlying NR1I2 negative feed-back regulation in hepatic cells. Additionally, glucocorticoids upregulated NR1I2 expression not only through the promoter region but also via 3'-UTR regulation, which likely involves downregulation of miR-18a-5p. We conclude that miR-18a-5p is involved in the down-regulation of NR1I2 expression by its ligands and in the upregulation of NR1I2 mRNA expression by glucocorticoids in hepatic cells.

• Klíčová slova
• 3′-UTR, 3′-untranslated region, CAR, constitutive androstane receptor, CYP3A4, cytochrome P450 3A4, Cytochrome P450 3A4, DEX, dexamethasone, DMEs, drug metabolizing enzymes, DMSO, dimethyl sulfoxide, ER, estrogen receptor, GRα, glucocorticoid receptor α, Gene expression, Gluc, Gaussia luciferase, Glucocorticoid, LBD, ligand binding domain, MRE, miRNA-response element, MicroRNA, NR, nuclear receptor, PB, phenobarbital, PCN, pregnenolone 16α-carbonitrile, PHHs, primary human hepatocytes, PPARα, peroxisome proliferator-activated receptor α, PXR, pregnane X receptor, Pregnane X receptor, RXRα, retinoid X receptor α, Regulation, Rif, rifampicin, SEAP, secreted alkaline phosphatase, miRNA, microRNA,
• Publikační typ
• časopisecké články MeSH

Resveratrol (RSV) is a stilbene phytochemical common in food and red wine. RSV inhibits cytochrome P450 CYP3A4 activity and interacts with the pregnane X receptor (PXR), the central regulator of drug/xenobiotic metabolizing enzyme expression. In this work, we comprehensively examined the effects of 13 stilbenes (trans- and cis-resveratrol, trans- and cis-piceatannol, oxyresveratrol, pterostilbene, pinostilbene, a,b-dihydroresveratrol, trans- and cis-trismethoxyresveratrol, trans-3,4,5,4'-tetramethoxystilbene, trans-2,4,3',5'-tetramethoxystilbene, trans-4-methoxystilbene), on CYP3A4 and CYP2B6 mRNA induction, and on CYP3A4/5, CYP2C8/9/19, CYP2D6, CYP2A6, CYP2E1, CYP1A2 and CYP2B6 cytochrome P450 enzyme activities. Expression experiments in five different primary human hepatocyte preparations, reporter gene assays, and ligand binding assays with pregnane X (PXR) and constitutive androstane (CAR) receptors were performed. Inhibition of cytochrome P450 enzymes was examined in human microsomes. We found that only polymethoxylated stilbenes are prone to significantly induce CYP2B6 or CYP3A4 in primary human hepatocytes via pregnane X receptor (PXR) interaction. Natural resveratrol derivatives such as trans- and cis-RSV, oxyresveratrol, pinostilbene and pterostilbene significantly inhibit CYP3A4/5 enzymatic activities; however, only trans-RSV significantly inhibits CYP3A4/5 activity (both testosterone 6β-hydroxylation and midazolam 1´-hydroxylation) in micromolar concentrations by a non-competitive mechanism, suggesting a potential risk of food-drug interactions with CYP3A4/5 substrates.

• Klíčová slova
• Cytochrome P450, Drug metabolism, Food-drug interactions, Pregnane X receptor, Resveratrol, Stilbenes,
• MeSH
• hepatocyty účinky léků   MeSH
• inhibitory cytochromu P450 metabolismus   MeSH
• interakce mezi potravou a léky * MeSH
• kultivované buňky MeSH
• lidé MeSH
• resveratrol MeSH
• steroidní receptory metabolismus   MeSH
• stilbeny metabolismus   farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• inhibitory cytochromu P450 MeSH
• resveratrol MeSH
• steroidní receptory MeSH
• stilbeny MeSH

The constitutive androstane receptor (CAR) is a nuclear receptor involved mainly in xenobiotic and endobiotic metabolism regulation. CAR is activated directly by its ligands via the ligand binding domain (LBD) or indirectly by inhibition of the epidermal growth factor (EGF) signaling. We found that leflunomide (LEF) and its main metabolite teriflunomide (TER), both used for autoimmune diseases treatment, induce the prototype CAR target gene CYP2B6 in primary human hepatocytes. As TER was discovered to be an EGF receptor antagonist, we sought to determine if TER is an indirect activator of CAR. In primary human hepatocytes and in differentiated HepaRG cells, we found that LEF and TER up-regulate CAR target genes CYP2B6 and CYP3A4 mRNAs and enzymatic activities. TER stimulated CAR+A mutant translocation into the nucleus but neither LEF nor TER activated the CAR LBD, CAR3 variant or pregnane X receptor (PXR) in gene reporter assays. Interestingly, TER significantly up-regulated CAR mRNA expression, a result which could be a consequence of both EGF receptor and ELK-1 transcription factor inhibition by TER or by TER-mediated activation of glucocorticoid receptor (GR), an upstream hormonal regulator of CAR. We can conclude that TER is a novel indirect CAR activator which through EGF inhibition and GR activation controls both detoxification and some intermediary metabolism genes.

• Klíčová slova
• CAR, cytochrome P450, gene regulation, metabolism, nuclear receptor,
• Publikační typ
• časopisecké články MeSH

AIM: To investigate the effect of resveratrol on biliary secretion of cholephilic compounds in healthy and bile duct-obstructed rats. METHODS: Resveratrol (RSV) or saline were administered to rats by daily oral gavage for 28 d after sham operation or reversible bile duct obstruction (BDO). Bile was collected 24 h after the last gavage during an intravenous bolus dose of the Mdr1/Mrp2 substrate azithromycin. Bile acids, glutathione and azithromycin were measured in bile to quantify their level of biliary secretion. Liver expression of enzymes and transporters relevant for bile production and biliary secretion of major bile constituents and drugs were analyzed at the mRNA and protein levels using qRT-PCR and Western blot analysis, respectively. The TR-FRET PXR Competitive Binding Assay kit was used to determine the agonism of RSV at the pregnane X receptor. RESULTS: RSV increased bile flow in sham-operated rats due to increased biliary secretion of bile acids (BA) and glutathione. This effect was accompanied by the induction of the hepatic rate-limiting transporters for bile acids and glutathione, Bsep and Mrp2, respectively. RSV also induced Cyp7a1, an enzyme that is crucial for bile acid synthesis; Mrp4, a transporter important for BA secretion from hepatocytes to blood; and Mdr1, the major apical transporter for xenobiotics. The findings were supported by increased biliary secretion of azithromycin. The TR-FRET PXR competitive binding assay confirmed RSV as a weak agonist of the human nuclear receptor PXR, which is a transcriptional regulator of Mdr1/Mrp2. RSV demonstrated significant hepatoprotective properties against BDO-induced cirrhosis. RSV also reduced bile flow in BDO rats without any corresponding change in the levels of the transporters and enzymes involved in RSV-mediated hepatoprotection. CONCLUSION: Resveratrol administration for 28 d has a distinct effect on bile flow and biliary secretion of cholephilic compounds in healthy and bile duct-obstructed rats.

• Klíčová slova
• Azithromycin, Bile acids, Bile production, Pregnane X receptor, Resveratrol,
• MeSH
• ABC transportéry metabolismus   MeSH
• antiflogistika nesteroidní farmakologie   terapeutické užití   MeSH
• antioxidancia farmakologie   terapeutické užití   MeSH
• aplikace orální MeSH
• azithromycin farmakokinetika   MeSH
• cholestáza farmakoterapie   etiologie   patofyziologie   MeSH
• glutathion metabolismus   MeSH
• hepatocyty účinky léků   metabolismus   MeSH
• játra účinky léků   metabolismus   patofyziologie   MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• potkani Wistar MeSH
• pregnanový X receptor MeSH
• resveratrol MeSH
• steroidní receptory agonisté   MeSH
• stilbeny farmakologie   terapeutické užití   MeSH
• žlučové kyseliny a soli chemie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ABC transportéry MeSH
• antiflogistika nesteroidní MeSH
• antioxidancia MeSH
• azithromycin MeSH
• glutathion MeSH
• pregnanový X receptor MeSH
• resveratrol MeSH
• steroidní receptory MeSH
• stilbeny MeSH
• žlučové kyseliny a soli MeSH

Stevia rebaudiana Bertoni is a herb known for the high content of natural sweeteners in its leaves. Its main secondary metabolite stevioside is used as non-caloric sweetener. No information, however, is available on whether stevioside or steviol interact with drug-metabolizing enzymes and pose the potential risk of food-drug interactions. Similarly, data are lacking on the interactions of steviol and stevioside with key nuclear receptors controlling the expression of the main drug metabolizing enzymes. We studied the interactions of steviol and stevioside with the pregnane X (PXR), vitamin D (VDR), constitutive androstane (CAR), farnesoid X (FXR), glucocorticoid (GR) and aryl hydrocarbon (AHR) receptors, which control expression of genes of xenobiotic metabolism. In addition, the inhibitory activities of steviol and stevioside towards the major cytochrome P450 enzymes CYP3A4, CYP2C9, CYP2D6, CYP1A2 and CYP2B6 were evaluated in vitro. We found that steviol moderately activated the PXR and AHR, resulting in the induction of their target genes including CYP3A4 and CYP1A2 in primary human hepatocytes. A weak inhibition of CYP3A4 and CYP2C9 with steviol was also found. Our results provide mechanistic data indicating that stevioside and stevia sweeteners may have the potential to induce food-drug interactions, a finding that warrants future prospective clinical investigation.

• Klíčová slova
• Drug metabolism, Food-drug interactions, Nuclear receptors, Steviol, Stevioside,
• MeSH
• cytochrom P-450 CYP1A2 genetika   metabolismus   MeSH
• diterpeny kauranové metabolismus   MeSH
• hepatocyty metabolismus   MeSH
• kultivované buňky MeSH
• lidé MeSH
• metabolická inaktivace MeSH
• pregnanový X receptor MeSH
• receptory aromatických uhlovodíků genetika   metabolismus   MeSH
• rostlinné extrakty metabolismus   MeSH
• senioři MeSH
• sladidla metabolismus   MeSH
• steroidní receptory genetika   metabolismus   MeSH
• Stevia chemie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cytochrom P-450 CYP1A2 MeSH
• diterpeny kauranové MeSH
• pregnanový X receptor MeSH
• receptory aromatických uhlovodíků MeSH
• rostlinné extrakty MeSH
• sladidla MeSH
• steroidní receptory MeSH
• steviol MeSH Prohlížeč

The Pregnane X (PXR), Vitamin D (VDR) and Farnesoid X (FXR) nuclear receptors have been shown to be receptors of bile acids controlling their detoxification or synthesis. Chenodeoxycholic (CDCA) and lithocholic (LCA) acids are ligands of FXR and VDR, respectively, whereas 3-keto and acetylated derivates of LCA have been described as ligands for all three receptors. In this study, we hypothesized that oxidation or acetylation at position 3, 7 and 12 of bile acids DCA (deoxycholic acid), LCA, CA (cholic acid), and CDCA by detoxification enzymes or microbiome may have an effect on the interactions with bile acid nuclear receptors. We employed reporter gene assays in HepG2 cells, the TR-FRET assay with recombinant PXR and RT-PCR to study the effects of acetylated and keto bile acids on the nuclear receptors activation and their target gene expression in differentiated hepatic HepaRG cells. We demonstrate that the DCA 3,12-diacetate and CA 3,7,12-triacetate derivatives are ligands of PXR and DCA 3,12-diacetate induces PXR target genes such as CYP3A4, CYP2B6 and ABCB1/MDR1. In conclusion, we found that acetylated DCA and CA are potent ligands of PXR. Whether the acetylated bile acid derivatives are novel endogenous ligands of PXR with detoxification or physiological functions should be further studied in ongoing experiments.

• Klíčová slova
• Bile acids, FXR, Metabolism, Nuclear receptors, PXR,
• MeSH
• acetylace MeSH
• buněčné kultury MeSH
• buňky Hep G2 MeSH
• cytochrom P-450 CYP3A genetika   MeSH
• cytochrom P450 CYP2B6 genetika   MeSH
• hepatocyty účinky léků   enzymologie   metabolismus   MeSH
• kyselina cholová chemie   metabolismus   farmakologie   MeSH
• kyselina deoxycholová chemie   metabolismus   farmakologie   MeSH
• lidé MeSH
• ligandy MeSH
• myši MeSH
• oxidace-redukce MeSH
• P-glykoprotein genetika   MeSH
• plazmidy MeSH
• pregnanový X receptor MeSH
• receptory cytoplazmatické a nukleární chemie   genetika   metabolismus   MeSH
• receptory kalcitriolu chemie   genetika   metabolismus   MeSH
• reportérové geny MeSH
• simulace molekulového dockingu MeSH
• steroidní receptory chemie   genetika   metabolismus   MeSH
• techniky dvojhybridového systému MeSH
• transfekce MeSH
• vazba proteinů MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cytochrom P-450 CYP3A MeSH
• cytochrom P450 CYP2B6 MeSH
• farnesoid X-activated receptor MeSH Prohlížeč
• kyselina cholová MeSH
• kyselina deoxycholová MeSH
• ligandy MeSH
• P-glykoprotein MeSH
• pregnanový X receptor MeSH
• receptory cytoplazmatické a nukleární MeSH
• receptory kalcitriolu MeSH
• steroidní receptory MeSH

Constitutive androstane receptor (CAR) is a key regulator of xenobiotic and endobiotic metabolism. Together with pregnane X (PXR) and aryl hydrocarbon (AHR) receptors, it is referred to as "xenobiotic receptor". The unique properties of human CAR, such as its high constitutive activity, both direct (ligand-binding domain-dependent) and indirect activation have hindered the discovery of direct selective human CAR ligands. Herein, we report a novel class of direct human CAR agonists in a group of 2-(3-methoxyphenyl)quinazoline derivatives. The compounds are even more potent activators of human CAR than is prototype 6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime (CITCO). The three most potent ligands are at the same time extremely potent activators of the other xenobiotic or hormonal receptors, namely PXR, AHR, and vitamin D receptor, which regulate major xenobiotic-metabolizing enzymes and efflux transporters. Thus, the novel CAR ligands can be also considered as constituting the first class of potent pan-xenobiotic receptor ligands that can serve as potential antidotes boosting overall metabolic elimination of xenobiotic or toxic compounds.

• MeSH
• buňky Hep G2 MeSH
• chinazoliny chemická syntéza   chemie   farmakologie   MeSH
• hepatocyty účinky léků   metabolismus   MeSH
• inhibitory enzymů chemická syntéza   chemie   farmakologie   MeSH
• konstitutivní androstanový receptor MeSH
• lidé MeSH
• molekulární modely MeSH
• molekulární struktura MeSH
• receptory cytoplazmatické a nukleární agonisté   MeSH
• systém (enzymů) cytochromů P-450 metabolismus   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• chinazoliny MeSH
• inhibitory enzymů MeSH
• konstitutivní androstanový receptor MeSH
• receptory cytoplazmatické a nukleární MeSH
• systém (enzymů) cytochromů P-450 MeSH

The organic cation transporter 1 (OCT1) is the dominant carrier of organic cationic drugs and some positively charged endogenous compounds into hepatocytes. OCT1 has unique expression pattern. It has the highest expression among drug transporters in normal human hepatocytes with large interindividual variability, but it has negligible expression in other tissues or their tumors. Nowadays, it is clear that the regulation of SLC22A1 gene encoding OCT1 transporter is rather complex and that transactivation with hepatocyte nuclear factor 4α (HNF4α) and CCAAT-enhancer-binding protein (C/EBPs) transcription factors as well as epigenetic regulation contribute to its unique hepatocyte-specific expression pattern. Unfortunately, species- and tissue-specific regulation of OCT1 and its orthologs as well as significant down-regulation in most immortalized cell lines hamper the study of SLC22A1 gene regulation. In the current review, we summarize our current understanding of human OCT1 transporter hepatic gene regulation and we propose potential post-transcriptional regulation by predicted miRNAs. We also discuss in detail recent findings on indirect regulation of the transporter via farnesoid X receptor (FXR), glucocorticoid receptor and pregnane X (PXR) receptor, which point out to potential novel mechanisms of xenobiotic-transporting and drug-metabolizing proteins regulation in the human liver as well as to potentially novel drug-drug interaction mechanisms. We also propose that comprehensive understanding of mechanisms of SLC22A1 gene regulation could direct research for other drug transporters and drug-metabolizing enzymes highly expressed in hepatocytes and controlled by HNF4α or other liver-enriched transcription factors.

• Klíčová slova
• Gene regulation, hepatic uptake, liver, nuclear receptors, organic cation transporter 1, transporter,
• MeSH
• epigeneze genetická MeSH
• hepatocytární jaderný faktor 4 metabolismus   MeSH
• hepatocyty metabolismus   MeSH
• lidé MeSH
• mikro RNA metabolismus   MeSH
• pregnanový X receptor MeSH
• přenašeč organických kationtů 1 metabolismus   MeSH
• proteiny vázající zesilovač transkripce CCAAT metabolismus   MeSH
• receptory cytoplazmatické a nukleární metabolismus   MeSH
• receptory glukokortikoidů metabolismus   MeSH
• regulace genové exprese * MeSH
• steroidní receptory metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• farnesoid X-activated receptor MeSH Prohlížeč
• hepatocytární jaderný faktor 4 MeSH
• mikro RNA MeSH
• pregnanový X receptor MeSH
• přenašeč organických kationtů 1 MeSH
• proteiny vázající zesilovač transkripce CCAAT MeSH
• receptory cytoplazmatické a nukleární MeSH
• receptory glukokortikoidů MeSH
• steroidní receptory MeSH

BACKGROUND AND PURPOSE: The organic cation transporter 1 (OCT1) transports cationic drugs into hepatocytes. The high hepatic expression of OCT1 is controlled by the HNF4α and USF transcription factors. Pregnane X receptor (PXR) mediates induction of the principal xenobiotic metabolizing enzymes and transporters in the liver. Here, we have assessed the down-regulation of OCT1 expression by PXR activation. EXPERIMENTAL APPROACH: We used primary human hepatocytes and related cell lines to measure OCT1 expression and activity, by assaying MPP(+) accumulation. Western blotting, qRT-PCR, the OCT1 promoter gene reporter constructs and chromatin immunoprecipitation assays were also used. KEY RESULTS: OCT1 mRNA in human hepatocytes was down-regulated along with reduced [(3) H]MPP(+) accumulation in differentiated HepaRG cells after treatment with rifampicin. Rifampicin and hyperforin as well as the constitutively active PXR mutant T248D suppressed activity of the 1.8 kb OCT1 promoter construct in gene reporter assays. Silencing of both PXR and HNF4α in HepaRG cells blocked the PXR ligand-mediated down-regulation of OCT1 expression. The mutation of HNF4α and USF1 (E-box) responsive elements reversed the PXR-mediated inhibition in gene reporter assays. Chromatin immunoprecipitation assays indicated that PXR activation sequestrates the SRC-1 coactivator from the HNF4α response element and E-box of the OCT1 promoter. Consistent with these findings, exogenous overexpression of the SRC-1, but not the PGC1α coactivator, relieved the PXR-mediated repression of OCT1 transactivation. CONCLUSIONS AND IMPLICATIONS: PXR ligands reduced the HNF4α-mediated and USF-mediated transactivation of OCT1 gene expression by competing for SRC-1 and decreased delivery of a model OCT1 substrate into hepatocytes.

• MeSH
• buňky Hep G2 MeSH
• down regulace MeSH
• floroglucinol analogy a deriváty   farmakologie   MeSH
• hepatocyty metabolismus   MeSH
• koaktivátor 1 jaderných receptorů metabolismus   MeSH
• lidé MeSH
• nádorové buňky kultivované MeSH
• oktamerní transkripční faktor 1 genetika   metabolismus   MeSH
• pregnanový X receptor MeSH
• rifampin farmakologie   MeSH
• steroidní receptory metabolismus   MeSH
• terpeny farmakologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• floroglucinol MeSH
• hyperforin MeSH Prohlížeč
• koaktivátor 1 jaderných receptorů MeSH
• NCOA1 protein, human MeSH Prohlížeč
• oktamerní transkripční faktor 1 MeSH
• POU2F1 protein, human MeSH Prohlížeč
• pregnanový X receptor MeSH
• rifampin MeSH
• steroidní receptory MeSH
• terpeny MeSH