Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOSH9L5)

• DOT Name: CTTNBP2 N-terminal-like protein (CTTNBP2NL)
• Gene Name: CTTNBP2NL
• UniProt ID: CT2NL_HUMAN
• Pfam ID: PF09727
• Sequence:
  MNLEKLSKPELLTLFSILEGELEARDLVIEALKAQHRDTFIEERYGKYNISDPLMALQRD
  FETLKEKNDGEKQPVCTNPLSILKVVMKQCKNMQERMLSQLAAAESRHRKVILDLEEERQ
  RHAQDTAEGDDVTYMLEKERERLTQQLEFEKSQVKKFEKEQKKLSSQLEEERSRHKQLSS
  MLVLECKKATNKAAEEGQKAGELSLKLEKEKSRVSKLEEELAAERKRGLQTEAQVEKQLS
  EFDIEREQLRAKLNREENRTKTLKEEMESLKKIVKDLEASHQHSSPNEQLKKPVTVSKGT
  ATEPLMLMSVFCQTESFPAERTHGSNIAKMTNTGLPGPATPAYSYAKTNGHCDPEIQTTR
  ELTAGNNVENQVPPREKSVALAQEKPVENGGCPVGIETPVPMPSPLSSSGSSLSPSSTAS
  SSLTSSPCSSPVLTKRLLGSSASSPGYQSSYQVGINQRFHAARHKFQSQADQDQQASGLQ
  SPPSRDLSPTLIDNSAAKQLARNTVTQVLSRFTSQQGPIKPVSPNSSPFGTDYRNLANTA
  NPRGDTSHSPTPGKVSSPLSPLSPGIKSPTIPRAERGNPPPIPPKKPGLTPSPSATTPLT
  KTHSQAASLTTAEDLASSCSSNTVVANGKDVELLLPTSS
• Function: Regulates lamellipodial actin dynamics in a CTTN-dependent manner.

Molecular Interaction Atlas (MIA) of This DOT

4 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of CTTNBP2 N-terminal-like protein (CTTNBP2NL).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of CTTNBP2 N-terminal-like protein (CTTNBP2NL).	[7]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of CTTNBP2 N-terminal-like protein (CTTNBP2NL).	[9]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of CTTNBP2 N-terminal-like protein (CTTNBP2NL).	[9]

8 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 CTTNBP2 N-terminal-like protein (CTTNBP2NL).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of CTTNBP2 N-terminal-like protein (CTTNBP2NL).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of CTTNBP2 N-terminal-like protein (CTTNBP2NL).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of CTTNBP2 N-terminal-like protein (CTTNBP2NL).	[5]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of CTTNBP2 N-terminal-like protein (CTTNBP2NL).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of CTTNBP2 N-terminal-like protein (CTTNBP2NL).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of CTTNBP2 N-terminal-like protein (CTTNBP2NL).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of CTTNBP2 N-terminal-like protein (CTTNBP2NL).	[11]

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] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] 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.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.