Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTH029C)

• DTT Name: Retinoic acid receptor RXR-gamma (RXRG)
• Synonyms: Retinoid X receptor gamma; Nuclear receptor subfamily 2 group B member 3; NR2B3
• Gene Name: RXRG
• DTT Type: Successful target; [1]
• BioChemical Class: Nuclear hormone receptor
• UniProt ID: RXRG_HUMAN
• TTD ID: T46456
• Sequence:
  MYGNYSHFMKFPAGYGGSPGHTGSTSMSPSAALSTGKPMDSHPSYTDTPVSAPRTLSAVG
  TPLNALGSPYRVITSAMGPPSGALAAPPGINLVAPPSSQLNVVNSVSSSEDIKPLPGLPG
  IGNMNYPSTSPGSLVKHICAICGDRSSGKHYGVYSCEGCKGFFKRTIRKDLIYTCRDNKD
  CLIDKRQRNRCQYCRYQKCLVMGMKREAVQEERQRSRERAESEAECATSGHEDMPVERIL
  EAELAVEPKTESYGDMNMENSTNDPVTNICHAADKQLFTLVEWAKRIPHFSDLTLEDQVI
  LLRAGWNELLIASFSHRSVSVQDGILLATGLHVHRSSAHSAGVGSIFDRVLTELVSKMKD
  MQMDKSELGCLRAIVLFNPDAKGLSNPSEVETLREKVYATLEAYTKQKYPEQPGRFAKLL
  LRLPALRSIGLKCLEHLFFFKLIGDTPIDTFLMEMLETPLQIT
• Function: Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. The high affinity ligand for RXRs is 9-cis retinoic acid. Receptor for retinoic acid.
• KEGG Pathway:
  PPAR signaling pathway (hsa03320)
  Thyroid hormone signaling pathway (hsa04919)
  Adipocytokine signaling pathway (hsa04920)
  Pathways in cancer (hsa05200)
  Transcriptional misregulation in cancer (hsa05202)
  Thyroid cancer (hsa05216)
  Small cell lung cancer (hsa05222)
  Non-small cell lung cancer (hsa05223)
• Reactome Pathway: Nuclear Receptor transcription pathway (R-HSA-383280)

Molecular Interaction Atlas (MIA) of This DTT

2 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Alitretinoin	DMME8LH	Kaposi sarcoma	2B57	Approved	[2]
Vitamin A	DMJ2AH4	Night blindness	9D45	Approved	[1]

3 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
NRX-4204	DMYXOU2	Diabetic complication	5A2Y	Phase 2	[3]
9cUAB-30	DMYKPXJ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[4]
IRX4204	DM9SCME	Breast cancer	2C60-2C65	Phase 1	[5]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
SR-11237	DMQG3CK	Solid tumour/cancer	2A00-2F9Z	Terminated	[6]

2 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AGN-34	DM5ECDM	Discovery agent	N.A.	Investigative	[7]
LG100754	DMEK4FY	Discovery agent	N.A.	Investigative	[8]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Prostate cancer	2C82	Prostate	4.44E-02	-0.25	-0.41

References

• [1] Vitamins and cofactors: highlights of ESBOC 2009. Nat Chem Biol. 2009 Aug;5(8):530-3.
• [2] Retinoic acid receptors and retinoid X receptors: interactions with endogenous retinoic acids. Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):30-4.
• [3] DOI: 10.1038/scibx.2010.766
• [4] In vitro metabolic characterization, phenotyping, and kinetic studies of 9cUAB30, a retinoid X receptor-specific retinoid. Drug Metab Dispos. 2007 Jul;35(7):1157-64.
• [5] Selective brain penetrable Nurr1 transactivator for treating Parkinson's disease.Oncotarget.2016 Feb 16;7(7):7469-79.
• [6] Silicon analogues of the RXR-selective retinoid agonist SR11237 (BMS649): chemistry and biology. ChemMedChem. 2009 Jul;4(7):1143-52.
• [7] Farnesoid X receptor: from structure to potential clinical applications. J Med Chem. 2005 Aug 25;48(17):5383-403.
• [8] Activation of specific RXR heterodimers by an antagonist of RXR homodimers. Nature. 1996 Oct 3;383(6599):450-3.