Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBZQX97)

• DOT Name: Cell growth regulator with EF hand domain protein 1 (CGREF1)
• Synonyms: Cell growth regulatory gene 11 protein; Hydrophobestin
• Gene Name: CGREF1
• Related Disease: Liver cancer
• UniProt ID: CGRE1_HUMAN
• Sequence:
  MLPLTMTVLILLLLPTGQAAPKDGVTRPDSEVQHQLLPNPFQPGQEQLGLLQSYLKGLGR
  TEVQLEHLSREQVLLYLFALHDYDQSGQLDGLELLSMLTAALAPGAANSPTTNPVILIVD
  KVLETQDLNGDGLMTPAELINFPGVALRHVEPGEPLAPSPQEPQAVGRQSLLAKSPLRQE
  TQEAPGPREEAKGQVEARRESLDPVQEPGGQAEADGDVPGPRGEAEGQAEAKGDAPGPRG
  EAGGQAEAEGDAPGPRGEAGGQAEAEGDAPGPRGEAGGQAEARENGEEAKELPGETLESK
  NTQNDFEVHIVQVENDEI
• Function: Mediates cell-cell adhesion in a calcium-dependent manner. Able to inhibit growth in several cell lines.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Liver cancer	DISDE4BI	Strong	Biomarker	[1]

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 Cell growth regulator with EF hand domain protein 1 (CGREF1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Cell growth regulator with EF hand domain protein 1 (CGREF1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cell growth regulator with EF hand domain protein 1 (CGREF1).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cell growth regulator with EF hand domain protein 1 (CGREF1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Cell growth regulator with EF hand domain protein 1 (CGREF1).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Cell growth regulator with EF hand domain protein 1 (CGREF1).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Cell growth regulator with EF hand domain protein 1 (CGREF1).	[8]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Cell growth regulator with EF hand domain protein 1 (CGREF1).	[9]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Cell growth regulator with EF hand domain protein 1 (CGREF1).	[10]
Urethane	DM7NSI0	Phase 4	Urethane affects the expression of Cell growth regulator with EF hand domain protein 1 (CGREF1).	[11]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Cell growth regulator with EF hand domain protein 1 (CGREF1).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Cell growth regulator with EF hand domain protein 1 (CGREF1).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Cell growth regulator with EF hand domain protein 1 (CGREF1).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Cell growth regulator with EF hand domain protein 1 (CGREF1).	[14]

References

• [1] Discriminating between adaptive and carcinogenic liver hypertrophy in rat studies using logistic ridge regression analysis of toxicogenomic data: The mode of action and predictive models.Toxicol Appl Pharmacol. 2017 Mar 1;318:79-87. doi: 10.1016/j.taap.2017.01.006. Epub 2017 Jan 18.
• [2] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 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.
• [8] 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.
• [9] Induction of heme oxygenase-1 by cobalt protoporphyrin enhances the antitumour effect of bortezomib in adult T-cell leukaemia cells. Br J Cancer. 2007 Oct 22;97(8):1099-105. doi: 10.1038/sj.bjc.6604003. Epub 2007 Sep 25.
• [10] Characterizing the genetic basis for nicotine induced cancer development: a transcriptome sequencing study. PLoS One. 2013 Jun 18;8(6):e67252.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [13] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [14] 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.