Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB1WOZA)

• DOT Name: Dehydrogenase/reductase SDR family member 9 (DHRS9)
• Synonyms: EC 1.1.1.209; EC 1.1.1.53; 3-alpha hydroxysteroid dehydrogenase; 3-alpha-HSD; NADP-dependent retinol dehydrogenase/reductase; RDH-E2; RDHL; Retinol dehydrogenase 15; EC 1.1.1.105; Short chain dehydrogenase/reductase family 9C member 4; Short-chain dehydrogenase/reductase retSDR8; Tracheobronchial epithelial cell-specific retinol dehydrogenase; RDH-TBE
• Gene Name: DHRS9
• UniProt ID: DHRS9_HUMAN
• EC Number: 1.1.1.105; 1.1.1.209; 1.1.1.53
• Pfam ID: PF00106
• Sequence:
  MLFWVLGLLILCGFLWTRKGKLKIEDITDKYIFITGCDSGFGNLAARTFDKKGFHVIAAC
  LTESGSTALKAETSERLRTVLLDVTDPENVKRTAQWVKNQVGEKGLWGLINNAGVPGVLA
  PTDWLTLEDYREPIEVNLFGLISVTLNMLPLVKKAQGRVINVSSVGGRLAIVGGGYTPSK
  YAVEGFNDSLRRDMKAFGVHVSCIEPGLFKTNLADPVKVIEKKLAIWEQLSPDIKQQYGE
  GYIEKSLDKLKGNKSYVNMDLSPVVECMDHALTSLFPKTHYAAGKDAKIFWIPLSHMPAA
  LQDFLLLKQKAELANPKAV
• Function: 3-alpha-hydroxysteroid dehydrogenase that converts 3-alpha-tetrahydroprogesterone (allopregnanolone) to dihydroxyprogesterone and 3-alpha-androstanediol to dihydroxyprogesterone. Also plays a role in the biosynthesis of retinoic acid from retinaldehyde. Can utilize both NADH and NADPH.
• Tissue Specificity: Highly expressed in trachea and epidermis. Detected at lower levels in spinal cord, bone marrow, brain, tongue, esophagus, heart, colon, testis, placenta, lung, skeletal muscle and lymph node.
• 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:HS01113-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

16 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 Dehydrogenase/reductase SDR family member 9 (DHRS9).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Dehydrogenase/reductase SDR family member 9 (DHRS9).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Dehydrogenase/reductase SDR family member 9 (DHRS9).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Dehydrogenase/reductase SDR family member 9 (DHRS9).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Dehydrogenase/reductase SDR family member 9 (DHRS9).	[5]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Dehydrogenase/reductase SDR family member 9 (DHRS9).	[6]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Dehydrogenase/reductase SDR family member 9 (DHRS9).	[7]
Phenobarbital	DMXZOCG	Approved	Phenobarbital increases the expression of Dehydrogenase/reductase SDR family member 9 (DHRS9).	[8]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Dehydrogenase/reductase SDR family member 9 (DHRS9).	[9]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Dehydrogenase/reductase SDR family member 9 (DHRS9).	[10]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Dehydrogenase/reductase SDR family member 9 (DHRS9).	[11]
Alitretinoin	DMME8LH	Approved	Alitretinoin increases the expression of Dehydrogenase/reductase SDR family member 9 (DHRS9).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Dehydrogenase/reductase SDR family member 9 (DHRS9).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Dehydrogenase/reductase SDR family member 9 (DHRS9).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Dehydrogenase/reductase SDR family member 9 (DHRS9).	[14]
Octanal	DMTN0OK	Investigative	Octanal increases the expression of Dehydrogenase/reductase SDR family member 9 (DHRS9).	[15]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [3] Characterization of a novel airway epithelial cell-specific short chain alcohol dehydrogenase/reductase gene whose expression is up-regulated by retinoids and is involved in the metabolism of retinol. J Biol Chem. 2001 Jun 29;276(26):24194-202. doi: 10.1074/jbc.M100332200. Epub 2001 Apr 13.
• [4] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [5] 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.
• [6] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [7] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [8] Dose- and time-dependent effects of phenobarbital on gene expression profiling in human hepatoma HepaRG cells. Toxicol Appl Pharmacol. 2009 Feb 1;234(3):345-60.
• [9] 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.
• [10] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [11] 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.
• [12] Genome-wide transcriptional and functional analysis of human T lymphocytes treated with benzo[alpha]pyrene. Int J Mol Sci. 2018 Nov 17;19(11).
• [13] BET bromodomain protein inhibition is a therapeutic option for medulloblastoma. Oncotarget. 2013 Nov;4(11):2080-95.
• [14] Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.
• [15] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.