Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXSY21F)

• DOT Name: Ankyrin repeat domain-containing protein 37 (ANKRD37)
• Synonyms: Low-density lipoprotein receptor-related protein 2-binding protein; hLrp2bp
• Gene Name: ANKRD37
• UniProt ID: ANR37_HUMAN
• Pfam ID: PF12796
• Sequence:
  MLLLDCNPEVDGLKHLLETGASVNAPPDPCKQSPVHLAAGSGLACFLLWQLQTGADLNQQ
  DVLGEAPLHKAAKVGSLECLSLLVASDAQIDLCNKNGQTAEDLAWSCGFPDCAKFLTTIK
  CMQTIKASEHPDRNDCVAVLRQKRSLGSVENTSGKRKC
• Tissue Specificity: Mainly expressed in testis, small intestine, colon, blood leukocytes and in pancreatic adenocarcinoma cells.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Ankyrin repeat domain-containing protein 37 (ANKRD37).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Ankyrin repeat domain-containing protein 37 (ANKRD37).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Ankyrin repeat domain-containing protein 37 (ANKRD37).	[3]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Ankyrin repeat domain-containing protein 37 (ANKRD37).	[2]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Ankyrin repeat domain-containing protein 37 (ANKRD37).	[2]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Ankyrin repeat domain-containing protein 37 (ANKRD37).	[4]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Ankyrin repeat domain-containing protein 37 (ANKRD37).	[5]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Ankyrin repeat domain-containing protein 37 (ANKRD37).	[4]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Ankyrin repeat domain-containing protein 37 (ANKRD37).	[6]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Ankyrin repeat domain-containing protein 37 (ANKRD37).	[7]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Ankyrin repeat domain-containing protein 37 (ANKRD37).	[8]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Ankyrin repeat domain-containing protein 37 (ANKRD37).	[9]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of Ankyrin repeat domain-containing protein 37 (ANKRD37).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Ankyrin repeat domain-containing protein 37 (ANKRD37).	[12]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Ankyrin repeat domain-containing protein 37 (ANKRD37).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Ankyrin repeat domain-containing protein 37 (ANKRD37).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Ankyrin repeat domain-containing protein 37 (ANKRD37).	[15]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Ankyrin repeat domain-containing protein 37 (ANKRD37).	[6]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Ankyrin repeat domain-containing protein 37 (ANKRD37).	[16]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Ankyrin repeat domain-containing protein 37 (ANKRD37).	[17]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of Ankyrin repeat domain-containing protein 37 (ANKRD37).	[2]
Resorcinol	DMM37C0	Investigative	Resorcinol increases the expression of Ankyrin repeat domain-containing protein 37 (ANKRD37).	[18]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde increases the expression of Ankyrin repeat domain-containing protein 37 (ANKRD37).	[19]

1 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 affects the methylation of Ankyrin repeat domain-containing protein 37 (ANKRD37).	[11]

References

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• [2] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [3] 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.
• [4] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [5] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [6] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [7] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [8] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [9] Gene-expression profiling during curcumin-induced apoptosis reveals downregulation of CXCR4. Exp Hematol. 2007 Jan;35(1):84-95.
• [10] Human relevance of an in vitro gene signature in HaCaT for skin sensitization. Toxicol In Vitro. 2015 Feb;29(1):81-4. doi: 10.1016/j.tiv.2014.08.010. Epub 2014 Sep 16.
• [11] 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.
• [12] Targeting MYC dependence in cancer by inhibiting BET bromodomains. Proc Natl Acad Sci U S A. 2011 Oct 4;108(40):16669-74. doi: 10.1073/pnas.1108190108. Epub 2011 Sep 26.
• [13] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [14] 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.
• [15] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [16] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [17] Effects of nickel treatment on H3K4 trimethylation and gene expression. PLoS One. 2011 Mar 24;6(3):e17728. doi: 10.1371/journal.pone.0017728.
• [18] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [19] Gene expression profile and cytotoxicity of human bronchial epithelial cells exposed to crotonaldehyde. Toxicol Lett. 2010 Aug 16;197(2):113-22.