Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT09ZWHM)

• DOT Name: Spindlin-4 (SPIN4)
• Gene Name: SPIN4
• UniProt ID: SPIN4_HUMAN
• PDB ID: 4UY4
• Pfam ID: PF02513
• Sequence:
  MSPPTVPPMGVDGVSAYLMKKRHTHRKQRRKPTFLTRRNIVGCRIQHGWKEGNEPVEQWK
  GTVLEQVSVKPTLYIIKYDGKDSVYGLELHRDKRVLALEILPERVPTPRIDSRLADSLIG
  KAVEHVFEGEHGTKDEWKGMVLARAPVMDTWFYITYEKDPVLYMYTLLDDYKDGDLRIIP
  DSNYYFPTAEQEPGEVVDSLVGKQVEHAKDDGSKRTGIFIHQVVAKPSVYFIKFDDDIHI
  YVYGLVKTP
• Function: Exhibits H3K4me3-binding activity.

Molecular Interaction Atlas (MIA) of This DOT

20 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 Spindlin-4 (SPIN4).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Spindlin-4 (SPIN4).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Spindlin-4 (SPIN4).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Spindlin-4 (SPIN4).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Spindlin-4 (SPIN4).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Spindlin-4 (SPIN4).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Spindlin-4 (SPIN4).	[7]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Spindlin-4 (SPIN4).	[7]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Spindlin-4 (SPIN4).	[8]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Spindlin-4 (SPIN4).	[9]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Spindlin-4 (SPIN4).	[10]
Urethane	DM7NSI0	Phase 4	Urethane affects the expression of Spindlin-4 (SPIN4).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Spindlin-4 (SPIN4).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Spindlin-4 (SPIN4).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Spindlin-4 (SPIN4).	[15]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Spindlin-4 (SPIN4).	[8]
Milchsaure	DM462BT	Investigative	Milchsaure affects the expression of Spindlin-4 (SPIN4).	[16]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Spindlin-4 (SPIN4).	[5]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of Spindlin-4 (SPIN4).	[6]
Resorcinol	DMM37C0	Investigative	Resorcinol increases the expression of Spindlin-4 (SPIN4).	[9]

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 increases the methylation of Spindlin-4 (SPIN4).	[12]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] 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.
• [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] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [6] 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.
• [7] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [8] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [9] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [10] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] 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.
• [13] 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.
• [14] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [15] 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.
• [16] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.