pregnane x receptor

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.

TTA-A2 is a selective T-type calcium channel antagonist as a potent anticonvulsant that the Cav3.1 isoform plays a prominent role in mediating. TTA-A2 is equally potent against the Cav3.1 (a1G) and Cav3.2 (a1H) channels with IC50 values of 89 nM and 92 nM, respectively, at -80 and -100 mV holding potentials. TTA-A2 can be used for the research of a variety of human neurological diseases, including sleep disorders and epilepsy.

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.

Diethanolamine hydrochloride has a variety of biological activities and is an inhibitor of HSD17B4 (hydroxysteroid 17-beta dehydrogenase 4) and pregnane X receptor (PXR), as well as an agonist of p53 and an antagonist of Estrogen receptor.

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].

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.

SJYHJ-026 (compound 37) is a pregnane X receptor (PXR) degrader with a DC50 value of 86.6 nM and a maximum degradation efficacy of 66.4%. This compound demonstrates cytotoxicity in SNU-C4 HiBiT-PXR KI cells, with IC50 values of 97.4 μM (24 h) and 99.5 μM (72 h).

SJPUT-328 is a potent activator of the Pregnane X Receptor (PXR), which plays a crucial role in drug metabolism and drug interactions.

DL5050 is a selective agonist for the human constitutive androstane receptor (hCAR). This compound demonstrates superior affinity and selectivity for hCAR by inducing expression of CYP2B6 (the target of hCAR) at the mRNA and protein levels, rather than CYP3A4 (the target of the human pregnane X receptor, hPXR). As a selective hCAR agonist, DL5050 not only serves as a crucial tool molecule for studying hCAR's biological function but also holds potential as a lead compound for the development of therapeutic applications targeting hCAR.

4,8-Dioxa-3H-perfluorononanoic acid, a type of per- and polyfluoroalkyl substance (PFAS), exhibits affinity for the human pregnane X receptor (hPXR) and demonstrates potential agonistic activity.

FKK6 is a selective agonist of the pregnane X receptor (PXR) with an EC50 of 1.2 µM. It demonstrates strong affinity for plasma proteins and exhibits favorable metabolic characteristics in human microsomes. FKK6 inhibits the PXR-related NF-κB signaling pathway, reducing the expression of inflammatory factors and showing anti-inflammatory activity in a mouse model of DSS-induced colitis.

MI-883 is an orally active Constitutive Androstane Receptor (CAR, EC50=73 nM) agonist and a Pregnane X Receptor (PXR, IC50=0.1 μM) antagonist. It enhances CAR LBD assembly (EC50=0.38 µM) and activates the CAR3 variant (EC50=0.074 µM), inducing CYP2B6 mRNA expression in HepaRG and primary human hepatocytes. Additionally, MI-883 inhibits the basal activity of PXR (IC50=2.03 µM) and reduces CYP3A4 mRNA expression in transiently transfected HepG2 cells. It also regulates cholesterol metabolism and bile acid excretion, improving hypercholesterolemia in mouse models.

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.

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

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

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

Pyributicarb (TSH-888) is a potent activator of both CYP3A4 gene and human pregnane X receptor (hPXR).

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.

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.

JMV7048 is an effective PROTAC degrader targeting the PXR (Pregnane X Receptor), with a DC50 of 379 nM. It induces the polyubiquitination and degradation of PXR protein by recruiting the E3 CRBN ubiquitin ligase and the 26S proteasome. This degradation of PXR significantly enhances the chemosensitivity of colorectal cancer stem cells, substantially delaying cancer recurrence in vivo. The composition of JMV7048 includes the PXR agonist JMV6944, a linker, and Thalidomide 5-fluoride.

Hyperforin, a natural product from Hypericum, is commonly used as an antidepressant and also has neurological, inflammatory, antimicrobial, antitumor and antiangiogenic effects. Hyperforin acts as a monoamine reuptake inhibitor (MRI) in vitro, including serotonin, norepinephrine, dopamine, GABA, and glutamate, with an IC 50 of ≈0.1 μg/mL. Hyperforin is also capable of inducing the cytochrome P450 enzymes, CYP3A4 and CYP2C9, through binding to and activation of the pregnane X receptor. Hyperforin is capable of activating TRPC6 channels by binding to a specific motif.