Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT367U3E)

• DOT Name: Retinoic acid receptor beta (RARB)
• Synonyms: RAR-beta; HBV-activated protein; Nuclear receptor subfamily 1 group B member 2; RAR-epsilon
• Gene Name: RARB
• Related Disease:
  Microphthalmia, syndromic 12
  Matthew-Wood syndrome
• UniProt ID: RARB_HUMAN
• PDB ID: 1HRA; 1XAP; 4DM6; 4DM8; 4JYG; 4JYH; 4JYI; 5UAN; 6SSQ
• Pfam ID: PF00104 ; PF00105
• Sequence:
  MTTSGHACPVPAVNGHMTHYPATPYPLLFPPVIGGLSLPPLHGLHGHPPPSGCSTPSPAT
  IETQSTSSEELVPSPPSPLPPPRVYKPCFVCQDKSSGYHYGVSACEGCKGFFRRSIQKNM
  IYTCHRDKNCVINKVTRNRCQYCRLQKCFEVGMSKESVRNDRNKKKKETSKQECTESYEM
  TAELDDLTEKIRKAHQETFPSLCQLGKYTTNSSADHRVRLDLGLWDKFSELATKCIIKIV
  EFAKRLPGFTGLTIADQITLLKAACLDILILRICTRYTPEQDTMTFSDGLTLNRTQMHNA
  GFGPLTDLVFTFANQLLPLEMDDTETGLLSAICLICGDRQDLEEPTKVDKLQEPLLEALK
  IYIRKRRPSKPHMFPKILMKITDLRSISAKGAERVITLKMEIPGSMPPLIQEMLENSEGH
  EPLTPSSSGNTAEHSPSISPSSVENSGVSQSPLVQ
• Function: Receptor for retinoic acid. 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. The RXRA/RARB heterodimer can act as a repressor on the DR1 element and as an activator on the DR5 element. In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function.
• Tissue Specificity: Expressed in aortic endothelial cells (at protein level).
• KEGG Pathway:
  Pathways in cancer (hsa05200)
  Small cell lung cancer (hsa05222)
  Non-small cell lung cancer (hsa05223)
  Gastric cancer (hsa05226)
• Reactome Pathway:
  Signaling by Retinoic Acid (R-HSA-5362517)
  Activation of anterior HOX genes in hindbrain development during early embryogenesis (R-HSA-5617472)
  Nuclear Receptor transcription pathway (R-HSA-383280)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Microphthalmia, syndromic 12	DISCSXV3	Definitive	Autosomal dominant	[1]
Matthew-Wood syndrome	DISA7HR7	Supportive	Autosomal dominant	[2]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Retinoic acid receptor beta (RARB) decreases the response to substance of Tretinoin.	[41]

4 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Retinoic acid receptor beta (RARB).	[3]
Hydralazine	DMU8JGH	Approved	Hydralazine decreases the methylation of Retinoic acid receptor beta (RARB).	[22]
NVP-LAQ824	DM8JWNA	Phase 3	NVP-LAQ824 increases the acetylation of Retinoic acid receptor beta (RARB).	[27]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Retinoic acid receptor beta (RARB).	[31]

40 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Retinoic acid receptor beta (RARB).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Retinoic acid receptor beta (RARB).	[5]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Retinoic acid receptor beta (RARB).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Retinoic acid receptor beta (RARB).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Retinoic acid receptor beta (RARB).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Retinoic acid receptor beta (RARB).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Retinoic acid receptor beta (RARB).	[10]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Retinoic acid receptor beta (RARB).	[11]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Retinoic acid receptor beta (RARB).	[13]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Retinoic acid receptor beta (RARB).	[14]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Retinoic acid receptor beta (RARB).	[15]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Retinoic acid receptor beta (RARB).	[16]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Retinoic acid receptor beta (RARB).	[17]
Melphalan	DMOLNHF	Approved	Melphalan decreases the expression of Retinoic acid receptor beta (RARB).	[18]
Mitoxantrone	DMM39BF	Approved	Mitoxantrone increases the expression of Retinoic acid receptor beta (RARB).	[4]
Bicalutamide	DMZMSPF	Approved	Bicalutamide increases the expression of Retinoic acid receptor beta (RARB).	[19]
Beta-carotene	DM0RXBT	Approved	Beta-carotene increases the expression of Retinoic acid receptor beta (RARB).	[20]
Bexarotene	DMOBIKY	Approved	Bexarotene increases the expression of Retinoic acid receptor beta (RARB).	[21]
Vitamin A	DMJ2AH4	Approved	Vitamin A decreases the expression of Retinoic acid receptor beta (RARB).	[20]
Amsacrine	DMZKYIV	Approved	Amsacrine increases the expression of Retinoic acid receptor beta (RARB).	[4]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Retinoic acid receptor beta (RARB).	[23]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Retinoic acid receptor beta (RARB).	[13]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Retinoic acid receptor beta (RARB).	[24]
Fenretinide	DMRD5SP	Phase 3	Fenretinide increases the expression of Retinoic acid receptor beta (RARB).	[25]
Rigosertib	DMOSTXF	Phase 3	Rigosertib increases the expression of Retinoic acid receptor beta (RARB).	[26]
Peretinoin	DMESAZK	Phase 3	Peretinoin increases the expression of Retinoic acid receptor beta (RARB).	[28]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Retinoic acid receptor beta (RARB).	[29]
Amsilarotene	DMOB01U	Phase 2	Amsilarotene increases the expression of Retinoic acid receptor beta (RARB).	[30]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Retinoic acid receptor beta (RARB).	[32]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Retinoic acid receptor beta (RARB).	[33]
PD-153035	DM7KJTI	Discontinued in Phase 1	PD-153035 increases the expression of Retinoic acid receptor beta (RARB).	[4]
Scriptaid	DM9JZ21	Preclinical	Scriptaid increases the expression of Retinoic acid receptor beta (RARB).	[25]
Nobiletin	DM7R3B6	Preclinical	Nobiletin increases the expression of Retinoic acid receptor beta (RARB).	[34]
SR-11237	DMQG3CK	Terminated	SR-11237 increases the expression of Retinoic acid receptor beta (RARB).	[35]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Retinoic acid receptor beta (RARB).	[36]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Retinoic acid receptor beta (RARB).	[37]
all-trans-4-oxo-retinoic acid	DMM2R1N	Investigative	all-trans-4-oxo-retinoic acid increases the expression of Retinoic acid receptor beta (RARB).	[20]
15-deoxy-Delta(12, 14)-prostaglandin J(2)	DM8VUX3	Investigative	15-deoxy-Delta(12, 14)-prostaglandin J(2) increases the expression of Retinoic acid receptor beta (RARB).	[16]
chlordane	DMMHU8G	Investigative	chlordane increases the expression of Retinoic acid receptor beta (RARB).	[39]
CD2665	DM05M9X	Investigative	CD2665 increases the expression of Retinoic acid receptor beta (RARB).	[40]

2 Drug(s) Affected the Biochemical Pathways of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Decitabine	DMQL8XJ	Approved	Decitabine decreases the metabolism of Retinoic acid receptor beta (RARB).	[12]
CATECHIN	DMY38SB	Investigative	CATECHIN decreases the metabolism of Retinoic acid receptor beta (RARB).	[38]

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