Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTISP28)

• DTT Name: Retinoic acid receptor beta (RARB)
• Synonyms: RAR-epsilon; RAR-beta; Nuclear receptor subfamily 1 group B member 2; NR1B2; HBV-activated protein; HAP
• Gene Name: RARB
• DTT Type: Successful target; [1]
• BioChemical Class: Nuclear hormone receptor
• UniProt ID: RARB_HUMAN
• TTD ID: T61657
• Sequence:
  MTTSGHACPVPAVNGHMTHYPATPYPLLFPPVIGGLSLPPLHGLHGHPPPSGCSTPSPAT
  IETQSTSSEELVPSPPSPLPPPRVYKPCFVCQDKSSGYHYGVSACEGCKGFFRRSIQKNM
  IYTCHRDKNCVINKVTRNRCQYCRLQKCFEVGMSKESVRNDRNKKKKETSKQECTESYEM
  TAELDDLTEKIRKAHQETFPSLCQLGKYTTNSSADHRVRLDLGLWDKFSELATKCIIKIV
  EFAKRLPGFTGLTIADQITLLKAACLDILILRICTRYTPEQDTMTFSDGLTLNRTQMHNA
  GFGPLTDLVFTFANQLLPLEMDDTETGLLSAICLICGDRQDLEEPTKVDKLQEPLLEALK
  IYIRKRRPSKPHMFPKILMKITDLRSISAKGAERVITLKMEIPGSMPPLIQEMLENSEGH
  EPLTPSSSGNTAEHSPSISPSSVENSGVSQSPLVQ
• 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 RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence or presence of hormone ligand, acts mainly as an activator of gene expression due to weak binding to corepressors. In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function. Receptor for retinoic acid.
• KEGG Pathway:
  Pathways in cancer (hsa05200)
  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

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Alitretinoin	DMME8LH	Kaposi sarcoma	2B57	Approved	[1]

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tamibarotene	DM3G74J	T-cell leukaemia	2A90	Phase 3	[2]

3 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID27336223-Compound-10	DMYUP6G	N. A.	N. A.	Patented	[3]
PMID27336223-Compound-7	DM9QM6I	N. A.	N. A.	Patented	[3]
PMID27336223-Compound-8	DM460D1	N. A.	N. A.	Patented	[3]

6 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AC261066	DMSKE1I	Discovery agent	N.A.	Investigative	[4]
AC55649	DM4JNY9	Discovery agent	N.A.	Investigative	[4]
AGN193109	DMC0YOE	Discovery agent	N.A.	Investigative	[5]
BMS641	DMRT7G3	Discovery agent	N.A.	Investigative	[6]
CD666	DMC8X9Y	Discovery agent	N.A.	Investigative	[7]
TTNPB	DMSABD0	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
Alzheimer's disease	8A00.0	Entorhinal cortex	9.92E-02	-0.05	-0.21

References

• [1] 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.
• [2] Tamibarotene: a candidate retinoid drug for Alzheimer's disease. Biol Pharm Bull. 2012;35(8):1206-12.
• [3] Therapeutic use of selective synthetic ligands for retinoic acid receptors: a patent review.Expert Opin Ther Pat. 2016 Aug;26(8):957-71.
• [4] Discovery of a potent, orally available, and isoform-selective retinoic acid beta2 receptor agonist. J Med Chem. 2005 Dec 1;48(24):7517-9.
• [5] Therapeutic applications for ligands of retinoid receptors. Curr Pharm Des. 2000 Jan;6(1):25-58.
• [6] Rational design of RAR-selective ligands revealed by RARbeta crystal stucture. EMBO Rep. 2004 Sep;5(9):877-82.
• [7] Identification of synthetic retinoids with selectivity for human nuclear retinoic acid receptor gamma. Biochem Biophys Res Commun. 1992 Jul 31;186(2):977-83.
• [8] 9-cis-retinoic acid analogues with bulky hydrophobic rings: new RXR-selective agonists. Bioorg Med Chem Lett. 2004 Dec 20;14(24):6117-22.