Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2BXCL0)

• DOT Name: Triple QxxK/R motif-containing protein (TRIQK)
• Synonyms: Triple repetitive-sequence of QXXK/R protein homolog
• Gene Name: TRIQK
• Related Disease: Alzheimer disease
• UniProt ID: TRIQK_HUMAN
• Pfam ID: PF15168
• Sequence:
  MGRKDAATIKLPVDQYRKQIGKQDYKKTKPILRATKLKAEAKKTAIGIKEVGLVLAAILA
  LLLAFYAFFYLRLTTDVDPDLDQDED
• Function: May play a role in cell growth and maintenance of cell morphology.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[1]

13 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 Triple QxxK/R motif-containing protein (TRIQK).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Triple QxxK/R motif-containing protein (TRIQK).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Triple QxxK/R motif-containing protein (TRIQK).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Triple QxxK/R motif-containing protein (TRIQK).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Triple QxxK/R motif-containing protein (TRIQK).	[6]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Triple QxxK/R motif-containing protein (TRIQK).	[7]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Triple QxxK/R motif-containing protein (TRIQK).	[8]
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of Triple QxxK/R motif-containing protein (TRIQK).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Triple QxxK/R motif-containing protein (TRIQK).	[10]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Triple QxxK/R motif-containing protein (TRIQK).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Triple QxxK/R motif-containing protein (TRIQK).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Triple QxxK/R motif-containing protein (TRIQK).	[13]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Triple QxxK/R motif-containing protein (TRIQK).	[14]

References

• [1] Genome-wide association study of Alzheimer's disease endophenotypes at prediagnosis stages.Alzheimers Dement. 2018 May;14(5):623-633. doi: 10.1016/j.jalz.2017.11.006. Epub 2017 Dec 20.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [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] 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.
• [7] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [8] 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.
• [9] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [10] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [11] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [12] 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.
• [13] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [14] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.