Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIND43N)

• DOT Name: Retinol dehydrogenase 11 (RDH11)
• Synonyms: EC 1.1.1.300; Androgen-regulated short-chain dehydrogenase/reductase 1; HCV core-binding protein HCBP12; Prostate short-chain dehydrogenase/reductase 1; Retinal reductase 1; RalR1; Short chain dehydrogenase/reductase family 7C member 1
• Gene Name: RDH11
• Related Disease:
  Hepatocellular carcinoma
  Lymphoma
  Metastatic prostate carcinoma
  Retinitis pigmentosa
  Retinitis pigmentosa-juvenile cataract-short stature-intellectual disability syndrome
  Vitamin A deficiency
• UniProt ID: RDH11_HUMAN
• EC Number: 1.1.1.300
• Pfam ID: PF00106
• Sequence:
  MVELMFPLLLLLLPFLLYMAAPQIRKMLSSGVCTSTVQLPGKVVVVTGANTGIGKETAKE
  LAQRGARVYLACRDVEKGELVAKEIQTTTGNQQVLVRKLDLSDTKSIRAFAKGFLAEEKH
  LHVLINNAGVMMCPYSKTADGFEMHIGVNHLGHFLLTHLLLEKLKESAPSRIVNVSSLAH
  HLGRIHFHNLQGEKFYNAGLAYCHSKLANILFTQELARRLKGSGVTTYSVHPGTVQSELV
  RHSSFMRWMWWLFSFFIKTPQQGAQTSLHCALTEGLEILSGNHFSDCHVAWVSAQARNET
  IARRLWDVSCDLLGLPID
• Function: Retinol dehydrogenase with a clear preference for NADP. Displays high activity towards 9-cis, 11-cis and all-trans-retinol, and to a lesser extent on 13-cis-retinol. Exhibits a low reductive activity towards unsaturated medium-chain aldehydes such as cis -6-nonenal and no activity toward nonanal or 4-hydroxy-nonenal. Has no dehydrogenase activity towards steroid.
• Tissue Specificity: Predominantly expressed in the epithelial cells of prostate, in both basal and luminal secretory cell populations. Expressed at low levels in spleen, thymus, testis, ovary, small intestine, colon, peripherical blood leukocytes, kidney, adrenal gland and fetal liver. Not detected in prostatic fibromuscular stromal cells, endothelial cells, or infiltrating lymphocytes.
• KEGG Pathway:
  Retinol metabolism (hsa00830)
  Metabolic pathways (hsa01100)
  Biosynthesis of cofactors (hsa01240)
• Reactome Pathway:
  RA biosynthesis pathway (R-HSA-5365859)
  Retinoid metabolism and transport (R-HSA-975634)
  The canonical retinoid cycle in rods (twilight vision) (R-HSA-2453902)
• BioCyc Pathway: MetaCyc:HS01050-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[1]
Lymphoma	DISN6V4S	Strong	Altered Expression	[1]
Metastatic prostate carcinoma	DISVBEZ9	Strong	Biomarker	[2]
Retinitis pigmentosa	DISCGPY8	Strong	Genetic Variation	[3]
Retinitis pigmentosa-juvenile cataract-short stature-intellectual disability syndrome	DISGX883	Strong	Autosomal recessive	[4]
Vitamin A deficiency	DISBEPZO	Strong	Altered Expression	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Retinol dehydrogenase 11 (RDH11).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Retinol dehydrogenase 11 (RDH11).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Retinol dehydrogenase 11 (RDH11).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Retinol dehydrogenase 11 (RDH11).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Retinol dehydrogenase 11 (RDH11).	[10]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Retinol dehydrogenase 11 (RDH11).	[11]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Retinol dehydrogenase 11 (RDH11).	[12]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Retinol dehydrogenase 11 (RDH11).	[13]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Retinol dehydrogenase 11 (RDH11).	[14]
Haloperidol	DM96SE0	Approved	Haloperidol decreases the expression of Retinol dehydrogenase 11 (RDH11).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Retinol dehydrogenase 11 (RDH11).	[16]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Retinol dehydrogenase 11 (RDH11).	[18]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Retinol dehydrogenase 11 (RDH11).	[19]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Retinol dehydrogenase 11 (RDH11).	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Retinol dehydrogenase 11 (RDH11).	[17]

References

• [1] Interaction between hepatitis C virus core protein and translin protein--a possible molecular mechanism for hepatocellular carcinoma and lymphoma caused by hepatitis C virus.World J Gastroenterol. 2003 Feb;9(2):300-3. doi: 10.3748/wjg.v9.i2.300.
• [2] Proteomic Characterization of Prostate Cancer to Distinguish Nonmetastasizing and Metastasizing Primary Tumors and Lymph Node Metastases.Neoplasia. 2018 Feb;20(2):140-151. doi: 10.1016/j.neo.2017.10.009. Epub 2017 Dec 14.
• [3] New syndrome with retinitis pigmentosa is caused by nonsense mutations in retinol dehydrogenase RDH11. Hum Mol Genet. 2014 Nov 1;23(21):5774-80. doi: 10.1093/hmg/ddu291. Epub 2014 Jun 10.
• [4] Functional characterization of mouse RDH11 as a retinol dehydrogenase involved in dark adaptation in vivo. J Biol Chem. 2005 May 27;280(21):20413-20. doi: 10.1074/jbc.M413789200. Epub 2005 Mar 24.
• [5] Retinyl esters are elevated in progeny of retinol dehydrogenase 11 deficient dams.Chem Biol Interact. 2019 Apr 1;302:117-122. doi: 10.1016/j.cbi.2019.01.041. Epub 2019 Feb 4.
• [6] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [7] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [8] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [11] JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene. 2008 Aug 28;27(37):5033-44.
• [12] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [13] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [14] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [15] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [16] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [17] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [18] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [19] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.
• [20] Analysis of the prostate cancer cell line LNCaP transcriptome using a sequencing-by-synthesis approach. BMC Genomics. 2006 Sep 29;7:246. doi: 10.1186/1471-2164-7-246.