Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT7LCTF)

• DTT Name: Pregnane X receptor (NR1I2)
• Synonyms: Steroid and xenobiotic receptor; SXR; PXR; Orphan nuclear receptor PXR; Orphan nuclear receptor PAR1; Nuclear receptor subfamily 1 group I member 2
• Gene Name: NR1I2
• DTT Type: Literature-reported target; [1]
• BioChemical Class: Nuclear hormone receptor
• UniProt ID: NR1I2_HUMAN
• TTD ID: T82702
• Sequence:
  MEVRPKESWNHADFVHCEDTESVPGKPSVNADEEVGGPQICRVCGDKATGYHFNVMTCEG
  CKGFFRRAMKRNARLRCPFRKGACEITRKTRRQCQACRLRKCLESGMKKEMIMSDEAVEE
  RRALIKRKKSERTGTQPLGVQGLTEEQRMMIRELMDAQMKTFDTTFSHFKNFRLPGVLSS
  GCELPESLQAPSREEAAKWSQVRKDLCSLKVSLQLRGEDGSVWNYKPPADSGGKEIFSLL
  PHMADMSTYMFKGIISFAKVISYFRDLPIEDQISLLKGAAFELCQLRFNTVFNAETGTWE
  CGRLSYCLEDTAGGFQQLLLEPMLKFHYMLKKLQLHEEEYVLMQAISLFSPDRPGVLQHR
  VVDQLQEQFAITLKSYIECNRPQPAHRFLFLKIMAMLTELRSINAQHTQRLLRIQDIHPF
  ATPLMQELFGITGS
• Function: Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes. Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds.
• Reactome Pathway:
  SUMOylation of intracellular receptors (R-HSA-4090294)
  Nuclear Receptor transcription pathway (R-HSA-383280)

Molecular Interaction Atlas (MIA) of This DTT

6 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
3-keto-lithocholic acid	DM5LUED	Discovery agent	N.A.	Investigative	[2]
Hyperforin	DM2L3PE	Discovery agent	N.A.	Investigative	[3]
pregnenolone-16alpha-carbonitrile	DM0LW7G	Discovery agent	N.A.	Investigative	[4]
schisandrin A	DMWQ480	Discovery agent	N.A.	Investigative	[1]
trihydroxycholestane	DMSP56N	Discovery agent	N.A.	Investigative	[5]
WAY-214950	DM8ODI7	Discovery agent	N.A.	Investigative	[6]

References

• [1] Traditional Chinese medicines Wu Wei Zi (Schisandra chinensis Baill) and Gan Cao (Glycyrrhiza uralensis Fisch) activate pregnane X receptor and inc... J Pharmacol Exp Ther. 2006 Mar;316(3):1369-77.
• [2] The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity. Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3369-74.
• [3] Pregnane X receptor (PXR) regulates P-glycoprotein at the blood-brain barrier: functional similarities between pig and human PXR. J Pharmacol Exp Ther. 2009 Apr;329(1):141-9.
• [4] An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway. Cell. 1998 Jan 9;92(1):73-82.
• [5] Identification of bile acid precursors as endogenous ligands for the nuclear xenobiotic pregnane X receptor. Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):223-8.
• [6] Indazole-based liver X receptor (LXR) modulators with maintained atherosclerotic lesion reduction activity but diminished stimulation of hepatic tr... J Med Chem. 2008 Nov 27;51(22):7161-8.