Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGX20TE)

• DOT Name: Transforming acidic coiled-coil-containing protein 1 (TACC1)
• Synonyms: Gastric cancer antigen Ga55; Taxin-1
• Gene Name: TACC1
• Related Disease:
  Advanced cancer
  Cleft lip
  Gastric cancer
  Gastric neoplasm
  Glioblastoma multiforme
  Isolated cleft lip
  Stomach cancer
  Breast cancer
  Breast carcinoma
  Gliosarcoma
  Neoplasm
• UniProt ID: TACC1_HUMAN
• Pfam ID: PF05010
• Sequence:
  MAFSPWQILSPVQWAKWTWSAVRGGAAGEDEAGGPEGDPEEEDSQAETKSLSFSSDSEGN
  FETPEAETPIRSPFKESCDPSLGLAGPGAKSQESQEADEQLVAEVVEKCSSKTCSKPSEN
  EVPQQAIDSHSVKNFREEPEHDFSKISIVRPFSIETKDSTDISAVLGTKAAHGCVTAVSG
  KALPSSPPDALQDEAMTEGSMGVTLEASAEADLKAGNSCPELVPSRRSKLRKPKPVPLRK
  KAIGGEFSDTNAAVEGTPLPKASYHFSPEELDENTSPLLGDARFQKSPPDLKETPGTLSS
  DTNDSGVELGEESRSSPLKLEFDFTEDTGNIEARKALPRKLGRKLGSTLTPKIQKDGISK
  SAGLEQPTDPVARDGPLSQTSSKPDPSQWESPSFNPFGSHSVLQNSPPLSSEGSYHFDPD
  NFDESMDPFKPTTTLTSSDFCSPTGNHVNEILESPKKAKSRLITSGCKVKKHETQSLALD
  ACSRDEGAVISQISDISNRDGHATDEEKLASTSCGQKSAGAEVKGEPEEDLEYFECSNVP
  VSTINHAFSSSEAGIEKETCQKMEEDGSTVLGLLESSAEKAPVSVSCGGESPLDGICLSE
  SDKTAVLTLIREEIITKEIEANEWKKKYEETRQEVLEMRKIVAEYEKTIAQMIEDEQRTS
  MTSQKSFQQLTMEKEQALADLNSVERSLSDLFRRYENLKGVLEGFKKNEEALKKCAQDYL
  ARVKQEEQRYQALKIHAEEKLDKANEEIAQVRTKAKAESAALHAGLRKEQMKVESLERAL
  QQKNQEIEELTKICDELIAKLGKTD
• Function: Involved in transcription regulation induced by nuclear receptors, including in T3 thyroid hormone and all-trans retinoic acid pathways. Might promote the nuclear localization of the receptors. Likely involved in the processes that promote cell division prior to the formation of differentiated tissues.
• Tissue Specificity: Isoform 1, isoform 3 and isoform 5 are ubiquitous. Isoform 2 is strongly expressed in the brain, weakly detectable in lung and colon, and overexpressed in gastric cancer. Isoform 4 is not detected in normal tissues, but strong expression was found in gastric cancer tissues. Down-regulated in a subset of cases of breast cancer.

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Cleft lip	DISV3XW6	Strong	Genetic Variation	[2]
Gastric cancer	DISXGOUK	Strong	Biomarker	[3]
Gastric neoplasm	DISOKN4Y	Strong	Altered Expression	[3]
Glioblastoma multiforme	DISK8246	Strong	Genetic Variation	[4]
Isolated cleft lip	DIS2O2JV	Strong	Genetic Variation	[2]
Stomach cancer	DISKIJSX	Strong	Biomarker	[3]
Breast cancer	DIS7DPX1	moderate	Biomarker	[1]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[1]
Gliosarcoma	DIS985MG	moderate	FusionGene	[5]
Neoplasm	DISZKGEW	Limited	Altered Expression	[6]

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 Transforming acidic coiled-coil-containing protein 1 (TACC1).	[7]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Transforming acidic coiled-coil-containing protein 1 (TACC1).	[21]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Transforming acidic coiled-coil-containing protein 1 (TACC1).	[21]

21 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 Transforming acidic coiled-coil-containing protein 1 (TACC1).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Transforming acidic coiled-coil-containing protein 1 (TACC1).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Transforming acidic coiled-coil-containing protein 1 (TACC1).	[10]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Transforming acidic coiled-coil-containing protein 1 (TACC1).	[11]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Transforming acidic coiled-coil-containing protein 1 (TACC1).	[12]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Transforming acidic coiled-coil-containing protein 1 (TACC1).	[13]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Transforming acidic coiled-coil-containing protein 1 (TACC1).	[14]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Transforming acidic coiled-coil-containing protein 1 (TACC1).	[15]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Transforming acidic coiled-coil-containing protein 1 (TACC1).	[16]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Transforming acidic coiled-coil-containing protein 1 (TACC1).	[17]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Transforming acidic coiled-coil-containing protein 1 (TACC1).	[15]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Transforming acidic coiled-coil-containing protein 1 (TACC1).	[18]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of Transforming acidic coiled-coil-containing protein 1 (TACC1).	[12]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Transforming acidic coiled-coil-containing protein 1 (TACC1).	[18]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Transforming acidic coiled-coil-containing protein 1 (TACC1).	[19]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of Transforming acidic coiled-coil-containing protein 1 (TACC1).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Transforming acidic coiled-coil-containing protein 1 (TACC1).	[20]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Transforming acidic coiled-coil-containing protein 1 (TACC1).	[22]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Transforming acidic coiled-coil-containing protein 1 (TACC1).	[19]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Transforming acidic coiled-coil-containing protein 1 (TACC1).	[23]
Cycloheximide	DMGDA3C	Investigative	Cycloheximide increases the expression of Transforming acidic coiled-coil-containing protein 1 (TACC1).	[12]

References

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• [2] Molecular contribution to cleft palate production in cleft lip mice.Congenit Anom (Kyoto). 2014 May;54(2):94-9. doi: 10.1111/cga.12038.
• [3] Altered splicing pattern of TACC1 mRNA in gastric cancer.Cancer Genet Cytogenet. 2002 Nov;139(1):78-83. doi: 10.1016/s0165-4608(02)00607-6.
• [4] FGF receptors: cancer biology and therapeutics.Med Res Rev. 2014 Mar;34(2):280-300. doi: 10.1002/med.21288. Epub 2013 May 21.
• [5] Transforming fusions of FGFR and TACC genes in human glioblastoma.Science. 2012 Sep 7;337(6099):1231-5. doi: 10.1126/science.1220834. Epub 2012 Jul 26.
• [6] Deep Sequencing Reveals a Novel miR-22 Regulatory Network with Therapeutic Potential in Rhabdomyosarcoma.Cancer Res. 2016 Oct 15;76(20):6095-6106. doi: 10.1158/0008-5472.CAN-16-0709. Epub 2016 Aug 28.
• [7] 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.
• [8] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [9] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [12] Estrogen regulation in human breast cancer cells of new downstream gene targets involved in estrogen metabolism, cell proliferation and cell transformation. J Mol Endocrinol. 2004 Apr;32(2):397-414.
• [13] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [14] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [15] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [16] A genomic approach to predict synergistic combinations for breast cancer treatment. Pharmacogenomics J. 2013 Feb;13(1):94-104. doi: 10.1038/tpj.2011.48. Epub 2011 Nov 15.
• [17] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [18] 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.
• [19] Gene expression-signature of belinostat in cell lines is specific for histone deacetylase inhibitor treatment, with a corresponding signature in xenografts. Anticancer Drugs. 2009 Sep;20(8):682-92.
• [20] 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.
• [21] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [22] Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
• [23] Analysis of the prostate cancer cell line LNCaP transcriptome using a sequencing-by-synthesis approach. BMC Genomics. 2006 Sep 29;7:246. doi: 10.1186/1471-2164-7-246.