Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE5CMEP)

• DOT Name: MANSC domain-containing protein 1 (MANSC1)
• Synonyms: Loss of heterozygosity 12 chromosomal region 3 protein
• Gene Name: MANSC1
• UniProt ID: MANS1_HUMAN
• Pfam ID: PF07502
• Sequence:
  MFFGGEGSLTYTLVIICFLTLRLSASQNCLKKSLEDVVIDIQSSLSKGIRGNEPVYTSTQ
  EDCINSCCSTKNISGDKACNLMIFDTRKTARQPNCYLFFCPNEEACPLKPAKGLMSYRII
  TDFPSLTRNLPSQELPQEDSLLHGQFSQAVTPLAHHHTDYSKPTDISWRDTLSQKFGSSD
  HLEKLFKMDEASAQLLAYKEKGHSQSSQFSSDQEIAHLLPENVSALPATVAVASPHTTSA
  TPKPATLLPTNASVTPSGTSQPQLATTAPPVTTVTSQPPTTLISTVFTRAAATLQAMATT
  AVLTTTFQAPTDSKGSLETIPFTEISNLTLNTGNVYNPTALSMSNVESSTMNKTASWEGR
  EASPGSSSQGSVPENQYGLPFEKWLLIGSLLFGVLFLVIGLVLLGRILSESLRRKRYSRL
  DYLINGIYVDI
• Tissue Specificity: Widely expressed.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of MANSC domain-containing protein 1 (MANSC1).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of MANSC domain-containing protein 1 (MANSC1).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of MANSC domain-containing protein 1 (MANSC1).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of MANSC domain-containing protein 1 (MANSC1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of MANSC domain-containing protein 1 (MANSC1).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of MANSC domain-containing protein 1 (MANSC1).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of MANSC domain-containing protein 1 (MANSC1).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of MANSC domain-containing protein 1 (MANSC1).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of MANSC domain-containing protein 1 (MANSC1).	[9]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of MANSC domain-containing protein 1 (MANSC1).	[10]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of MANSC domain-containing protein 1 (MANSC1).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of MANSC domain-containing protein 1 (MANSC1).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of MANSC domain-containing protein 1 (MANSC1).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of MANSC domain-containing protein 1 (MANSC1).	[15]

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 decreases the methylation of MANSC domain-containing protein 1 (MANSC1).	[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] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [3] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [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] 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.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.