Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLTDGK7)

• DOT Name: Testican-1 (SPOCK1)
• Synonyms: Protein SPOCK
• Gene Name: SPOCK1
• UniProt ID: TICN1_HUMAN
• Pfam ID: PF07648 ; PF10591 ; PF00086
• Sequence:
  MPAIAVLAAAAAAWCFLQVESRHLDALAGGAGPNHGNFLDNDQWLSTVSQYDRDKYWNRF
  RDDDYFRNWNPNKPFDQALDPSKDPCLKVKCSPHKVCVTQDYQTALCVSRKHLLPRQKKG
  NVAQKHWVGPSNLVKCKPCPVAQSAMVCGSDGHSYTSKCKLEFHACSTGKSLATLCDGPC
  PCLPEPEPPKHKAERSACTDKELRNLASRLKDWFGALHEDANRVIKPTSSNTAQGRFDTS
  ILPICKDSLGWMFNKLDMNYDLLLDPSEINAIYLDKYEPCIKPLFNSCDSFKDGKLSNNE
  WCYCFQKPGGLPCQNEMNRIQKLSKGKSLLGAFIPRCNEEGYYKATQCHGSTGQCWCVDK
  YGNELAGSRKQGAVSCEEEQETSGDFGSGGSVVLLDDLEYERELGPKDKEGKLRVHTRAV
  TEDDEDEDDDKEDEVGYIW
• Function: May play a role in cell-cell and cell-matrix interactions. May contribute to various neuronal mechanisms in the central nervous system.

Molecular Interaction Atlas (MIA) of This DOT

3 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 Testican-1 (SPOCK1).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Testican-1 (SPOCK1).	[13]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Testican-1 (SPOCK1).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Testican-1 (SPOCK1).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Testican-1 (SPOCK1).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Testican-1 (SPOCK1).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Testican-1 (SPOCK1).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Testican-1 (SPOCK1).	[6]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Testican-1 (SPOCK1).	[7]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Testican-1 (SPOCK1).	[8]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Testican-1 (SPOCK1).	[9]
Enzalutamide	DMGL19D	Approved	Enzalutamide decreases the expression of Testican-1 (SPOCK1).	[10]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Testican-1 (SPOCK1).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Testican-1 (SPOCK1).	[11]
Curcumin	DMQPH29	Phase 3	Curcumin increases the expression of Testican-1 (SPOCK1).	[12]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Testican-1 (SPOCK1).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Testican-1 (SPOCK1).	[16]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Testican-1 (SPOCK1).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Testican-1 (SPOCK1).	[18]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Testican-1 (SPOCK1).	[19]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Testican-1 (SPOCK1).	[20]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Testican-1 (SPOCK1).	[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] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [3] 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.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
• [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] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [8] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [9] Evaluation of developmental toxicity using undifferentiated human embryonic stem cells. J Appl Toxicol. 2015 Feb;35(2):205-18.
• [10] 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.
• [11] 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.
• [12] Curcumin suppresses growth of mesothelioma cells in vitro and in vivo, in part, by stimulating apoptosis. Mol Cell Biochem. 2011 Nov;357(1-2):83-94. doi: 10.1007/s11010-011-0878-2. Epub 2011 May 19.
• [13] 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.
• [14] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [15] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [16] 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.
• [17] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [18] 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.
• [19] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [20] Molecular targets of chloropicrin in human airway epithelial cells. Toxicol In Vitro. 2017 Aug;42:247-254.
• [21] Linking site-specific loss of histone acetylation to repression of gene expression by the mycotoxin ochratoxin A. Arch Toxicol. 2018 Feb;92(2):995-1014.