Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIZ2VK8)

• DOT Name: Ankyrin repeat domain-containing protein 10 (ANKRD10)
• Gene Name: ANKRD10
• UniProt ID: ANR10_HUMAN
• Pfam ID: PF00023 ; PF12796
• Sequence:
  MSAAGAGAGVEAGFSSEELLSLRFPLHRACRDGDLATLCSLLQQTPHAHLASEDSFYGWT
  PVHWAAHFGKLECLVQLVRAGATLNVSTTRYAQTPAHIAAFGGHPQCLVWLIQAGANINK
  PDCEGETPIHKAARSGSLECISALVANGAHVDLRNASGLTAADIAQTQGFQECAQFLLNL
  QNCHLNHFYNNGILNGGHQNVFPNHISVGTNRKRCLEDSEDFGVKKARTEAQSLDSAVPL
  TNGDTEDDADKMHVDREFAVVTDMKNSSSVSNTLTNGCVINGHLDFPSTTPLSGMESRNG
  QCLTGTNGISSGLAPGQPFPSSQGSLCISGTEEPEKTLRANPELCGSLHLNGSPSSCIAS
  RPSWVEDIGDNLYYGHYHGFGDTAESIPELNSVVEHSKSVKVQERYDSAVLGTMHLHHGS

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Topotecan	DMP6G8T	Approved	Ankyrin repeat domain-containing protein 10 (ANKRD10) affects the response to substance of Topotecan.	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Ankyrin repeat domain-containing protein 10 (ANKRD10).	[1]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Ankyrin repeat domain-containing protein 10 (ANKRD10).	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Ankyrin repeat domain-containing protein 10 (ANKRD10).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Ankyrin repeat domain-containing protein 10 (ANKRD10).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Ankyrin repeat domain-containing protein 10 (ANKRD10).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Ankyrin repeat domain-containing protein 10 (ANKRD10).	[5]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Ankyrin repeat domain-containing protein 10 (ANKRD10).	[6]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Ankyrin repeat domain-containing protein 10 (ANKRD10).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Ankyrin repeat domain-containing protein 10 (ANKRD10).	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Ankyrin repeat domain-containing protein 10 (ANKRD10).	[9]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Ankyrin repeat domain-containing protein 10 (ANKRD10).	[10]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Ankyrin repeat domain-containing protein 10 (ANKRD10).	[11]
Etoposide	DMNH3PG	Approved	Etoposide decreases the expression of Ankyrin repeat domain-containing protein 10 (ANKRD10).	[12]
Melphalan	DMOLNHF	Approved	Melphalan increases the expression of Ankyrin repeat domain-containing protein 10 (ANKRD10).	[13]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of Ankyrin repeat domain-containing protein 10 (ANKRD10).	[14]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Ankyrin repeat domain-containing protein 10 (ANKRD10).	[15]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Ankyrin repeat domain-containing protein 10 (ANKRD10).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Ankyrin repeat domain-containing protein 10 (ANKRD10).	[17]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Ankyrin repeat domain-containing protein 10 (ANKRD10).	[18]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Ankyrin repeat domain-containing protein 10 (ANKRD10).	[19]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde decreases the expression of Ankyrin repeat domain-containing protein 10 (ANKRD10).	[21]

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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] 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.
• [4] 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.
• [5] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [6] Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population. Environ Health Perspect. 2008 Apr;116(4):524-31. doi: 10.1289/ehp.10861.
• [7] 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.
• [8] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [9] 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.
• [10] 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.
• [11] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [12] Genomic profiling uncovers a molecular pattern for toxicological characterization of mutagens and promutagens in vitro. Toxicol Sci. 2011 Jul;122(1):185-97.
• [13] Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
• [14] Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
• [15] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [16] 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.
• [17] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [18] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [19] Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.
• [20] 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.
• [21] Gene expression profile and cytotoxicity of human bronchial epithelial cells exposed to crotonaldehyde. Toxicol Lett. 2010 Aug 16;197(2):113-22.
• [22] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.