Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL9FSGF)

• DOT Name: Retinol dehydrogenase 10 (RDH10)
• Synonyms: EC 1.1.1.300; Short chain dehydrogenase/reductase family 16C member 4
• Gene Name: RDH10
• Related Disease:
  Non-small-cell lung cancer
  Carcinoma
  Glioma
  Hepatocellular carcinoma
  Neoplasm
  Thyroid tumor
• UniProt ID: RDH10_HUMAN
• EC Number: 1.1.1.300
• Pfam ID: PF00106
• Sequence:
  MNIVVEFFVVTFKVLWAFVLAAARWLVRPKEKSVAGQVCLITGAGSGLGRLFALEFARRR
  ALLVLWDINTQSNEETAGMVRHIYRDLEAADAAALQAGNGEEEILPHCNLQVFTYTCDVG
  KRENVYLTAERVRKEVGEVSVLVNNAGVVSGHHLLECPDELIERTMMVNCHAHFWTTKAF
  LPTMLEINHGHIVTVASSLGLFSTAGVEDYCASKFGVVGFHESLSHELKAAEKDGIKTTL
  VCPYLVDTGMFRGCRIRKEIEPFLPPLKPDYCVKQAMKAILTDQPMICTPRLMYIVTFMK
  SILPFEAVVCMYRFLGADKCMYPFIAQRKQATNNNEAKNGI
• Function: Retinol dehydrogenase with a clear preference for NADP. Converts all-trans-retinol to all-trans-retinal. Has no detectable activity towards 11-cis-retinol, 9-cis-retinol and 13-cis-retinol.
• Tissue Specificity: Detected in retina, kidney, liver, small intestine, placenta, lung, heart and skeletal muscle.
• KEGG Pathway:
  Retinol metabolism (hsa00830)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  RA biosynthesis pathway (R-HSA-5365859)
  The canonical retinoid cycle in rods (twilight vision) (R-HSA-2453902)
• BioCyc Pathway: MetaCyc:ENSG00000121039-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
Non-small-cell lung cancer	DIS5Y6R9	Definitive	Altered Expression	[1]
Carcinoma	DISH9F1N	Strong	Altered Expression	[2]
Glioma	DIS5RPEH	Strong	Altered Expression	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[4]
Neoplasm	DISZKGEW	Strong	Altered Expression	[5]
Thyroid tumor	DISLVKMD	Strong	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Retinol dehydrogenase 10 (RDH10).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Retinol dehydrogenase 10 (RDH10).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Retinol dehydrogenase 10 (RDH10).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Retinol dehydrogenase 10 (RDH10).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Retinol dehydrogenase 10 (RDH10).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Retinol dehydrogenase 10 (RDH10).	[11]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Retinol dehydrogenase 10 (RDH10).	[12]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Retinol dehydrogenase 10 (RDH10).	[13]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Retinol dehydrogenase 10 (RDH10).	[14]
Pioglitazone	DMKJ485	Approved	Pioglitazone increases the expression of Retinol dehydrogenase 10 (RDH10).	[15]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Retinol dehydrogenase 10 (RDH10).	[16]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Retinol dehydrogenase 10 (RDH10).	[18]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 increases the expression of Retinol dehydrogenase 10 (RDH10).	[19]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Retinol dehydrogenase 10 (RDH10).	[20]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Retinol dehydrogenase 10 (RDH10).	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Retinol dehydrogenase 10 (RDH10).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Retinol dehydrogenase 10 (RDH10).	[21]

References

• [1] Identification of genes associated with non-small-cell lung cancer promotion and progression.Lung Cancer. 2010 Feb;67(2):151-9. doi: 10.1016/j.lungcan.2009.04.010. Epub 2009 May 26.
• [2] Retinoid acid receptor expression is helpful to distinguish between adenoma and well-differentiated carcinoma in the thyroid.Virchows Arch. 2013 Jun;462(6):619-32. doi: 10.1007/s00428-013-1419-z. Epub 2013 May 4.
• [3] Retinol dehydrogenase 10 promotes metastasis of glioma cells via the transforming growth factor-/SMAD signaling pathway.Chin Med J (Engl). 2019 Oct 20;132(20):2430-2437. doi: 10.1097/CM9.0000000000000478.
• [4] Forced expression of RDH10 gene retards growth of HepG2 cells.Cancer Biol Ther. 2007 Feb;6(2):238-44. doi: 10.4161/cbt.6.2.3625. Epub 2007 Feb 25.
• [5] Retinol dehydrogenase-10 promotes development and progression of human glioma via the TWEAK-NF-B axis.Oncotarget. 2017 Oct 27;8(62):105262-105275. doi: 10.18632/oncotarget.22166. eCollection 2017 Dec 1.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [7] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [8] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [9] 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.
• [10] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [11] 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.
• [12] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [13] PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006 Oct 2;203(10):2351-62.
• [14] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [15] Peroxisome proliferator activated receptor gamma (PPAR-gama) ligand pioglitazone regulated gene networks in term human primary trophoblast cells. Reprod Toxicol. 2018 Oct;81:99-107.
• [16] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [17] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [18] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [19] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [20] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [21] 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.
• [22] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.