pxr

Specific PXR antagonist 70 is a selective pregnane X receptor (PXR) antagonist with an IC50 of 540 nM and Ki of 390 nM for human PCR and enhances the chemosensitivity of cancer cells.

Forskolin (Coleonol) is a natural product, an adenylate cyclase activator (EC50=0.5 μM). Forskolin increases cAMP levels, activates PXR and FXR, and induces autophagy. Forskolin produces positive inotropic effects in the heart, and has platelet anticoagulant and antihypertensive effects.

BMS-903452 is a potent and selective GPR119 agonist with an EC50 of 14 nM, indicated for the treatment of acute and chronic rodent diabetes. GPR119 is mainly expressed in pancreatic b cells and gastrointestinal endocrine cells. BMS-903452 shows no significant inhibitory effect on 9 cytochrome P450 enzymes (IC50 > 40 μM), does not activate PXR (EC50 > 50 μM), and is not toxic to liver (HEPG2) cell lines.

Cecropin B acetate induces NF-κB activation and suppresses CYP3A29 by disrupting the association of the PXR/retinoid X receptor alpha (RXR-α) complex with DNA sequences. Cecropin B acetate exhibits strong antimicrobial activity.

Praeruptorin B is an inhibitor of sterol regulatory element-binding proteins (SREBPs) and can significantly up-regulate CYP3A4 expression and activity via the PXR-mediated pathway.

SR12813 (GW 485801) is a pregnane X receptor (PXR) agonist.

CITCO inhibits growth and expansion of brain tumour stem cells (BTSCs) and has an EC50 of 49 nM over pregnane X receptor (PXR), and no activity on other nuclear receptors. CITCO is an imidazothiazole derivative and it also is a selective Constitutive androstane receptor (CAR) agonist.

1. Desmethoxyyangonin (5,6-Dehydrokavain) protects LPS or LPS/D-GalN-induced damages in cell or liver tissues mainly through de-regulating IKK/NFκB and Jak2/STAT3 signaling pathways. 2. The induction of CYP3A23 by dihydromethysticin and Desmethoxy yangonin involves transcription activation, probably through a PXR-independent or PXR-involved indirect mechanism.

Isosilybin (Isosilibinin) and Silybin might be suitable candidates to design potent PXR antagonists to prevent drug-drug interactions via CYP3A4 in cancer patients.

BMS-695735, a benzimidazole inhibitor of insulin-like growth factor-1 receptor, has broad-spectrum antitumor activity in vivo. It was found that BMS-695735 had strong inhibition of CYP3A4, induction of CYP3A4 mediated by PXR transactivation, poor water so

Lynestrenol is a synthetic progestational hormone, is the progesterone receptor agonist

Isoetharine mesylate salt (Isoetarine mesilate) is a β-adrenergic receptor agonist. it also is pregnane X receptor (PXR) activator capable of upregulating CYP450 expression.

Isopteropodine (Uncarine E) is an isoyohimbine-type octindole alkaloid isolated from Hamelia patens micropropagated and has antimicrobial activity and stimulates the immune system. Isopteropodine has antimicrobial activity and stimulates the immune system.Isopteropodine is a positive modulator of muscarinic M1 and 5-HT2 receptors and a PXR activator that induces contraction of the rat myometrium.

B-Raf IN 6 is a potent inhibitor (IC50: 1.7 nM) of the protein kinase B-Raf, which does not bind the secondary target PXR and is resistant to rapid metabolism.B-Raf IN 6 has shown research potential in cancer diseases.

Tolindate, a potent PXR agonist, demonstrates antifungal activity and possesses an EC50 value of 8.3 µM.

Dendrogenin A (DDA) is a compound acting as a selective liver X receptor (LXR) modulator, cholesterol epoxide hydrolase inhibitor (Ki = 120 nM), and a metabolic product of cholesterol, originating from 5,6α-epoxy cholesterol through histamine conjugation via DDA synthase. This compound is present in non-cancerous human mammary epithelial cells and melanocytes, but absent or minimally present in various breast carcinoma, melanoma cells, and isolated human breast tumor tissues. DDA impedes the activation of LXRβ and LXRα induced by 22(R)-hydroxy cholesterol (IC50s = 76 and 362 nM, respectively), yet it also functions as a partial LXR agonist, boosting the protein levels of Nur77, NOR-1, LC3-I, and LC3-II in B16/F10 murine melanoma cells. It shows a preference for LXRα and LXRβ modulation while displaying selectivity over other receptors including pregnane X receptor (PXR), and various others at a concentration of 2.5 µM. Moreover, DDA enhances LC3-II protein levels in cancer cells and prompts autophagic cell death at specific concentrations. Notably, DDA (0.37 µg/kg) has been shown to diminish tumor growth in melanoma and mammary cancer murine models and promotes cancer cell differentiation both in vitro and in vivo.

BYAKANGELICIN,a main furanocoumarin constituent isolated and characterized as an aldose reductase inhibitor,and is effective for the treatment of sugar cataracts and diabetic neuropathy and hence might be useful as a lead compound for the development of new type drugs for clinical use.

5α-Androstan-3β-ol, a steroidal androgen, demonstrates selective interaction with cellular components, showing affinity for the androgen receptor (AR) with an IC50 of 1.7 µM and activating the pregnane X receptor (PXR) in HepG2 cells with an EC50 of 0.8 µM. It selectively inhibits the hydroxylase activities of 16α- and 6β-hydroxylase over 16β- or 7α-hydroxylase, with IC50 values of 70 and 110 µM, compared to >150 µM for the latter enzymes, indicating a specificity in its enzyme inhibition profile. Additionally, administration of this compound at a dosage of 30 mg/kg results in a decrease in testis weight and sperm production in mice, highlighting its biological effects on male reproductive parameters.

CCCTP is a potent inhibitor of the 11β-HSD-1 enzyme with reduced pregnane-X receptor (PXR) transactivation activity.

7α-Hydroxy-4-cholesten-3-one is an intermediate in bile acid synthesis from cholesterol, a PXR agonist, and a biomarker for bile acid loss and diseases related to defective bile acid biosynthesis. It is also the physiological substrate for [CYP8B1].

Pregnenolone Carbonitrile (5-Pregnen-3β-ol-20-one-16α-carbonitrile) is an activator of rodent-PXR and induces the expression of CYP3A.

B-Raf IN 5 is a potent inhibitor of the protein kinase B-Raf (IC50: 2.0 nM). B-Raf IN 5 resists rapid metabolism and does not bind to the secondary target PXR.

Desmethyl bosentan, an active metabolite of the endothelin receptor antagonist bosentan, activates the pregnane X receptor (PXR) in CV-1 monkey kidney cells expressing the human receptor in a reporter assay at a concentration of 25 μM.

Cecropin B is a small antibacterial peptide from the giant silkmoth, Hyalophora cecropia.