Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0EICG3)

• DOT Name: Cysteine-rich protein 1 (CRIP1)
• Synonyms: CRP-1; Cysteine-rich heart protein; CRHP; hCRHP; Cysteine-rich intestinal protein; CRIP
• Gene Name: CRIP1
• Related Disease:
  Colon cancer
  Colon carcinoma
  Hepatocellular carcinoma
  Acute myelogenous leukaemia
  Acute myocardial infarction
  Advanced cancer
  Bone osteosarcoma
  Cervical cancer
  Cervical carcinoma
  Colorectal carcinoma
  Epilepsy
  Metastatic malignant neoplasm
  Osteosarcoma
  Pulmonary fibrosis
  Schizophrenia
  Thyroid gland carcinoma
  Bacterial infection
  Hypoglycemia
  Stroke
  Asthma
  Breast cancer
  Breast carcinoma
  Neoplasm
• UniProt ID: CRIP1_HUMAN
• Pfam ID: PF00412
• Sequence:
  MPKCPKCNKEVYFAERVTSLGKDWHRPCLKCEKCGKTLTSGGHAEHEGKPYCNHPCYAAM
  FGPKGFGRGGAESHTFK
• Function: Seems to have a role in zinc absorption and may function as an intracellular zinc transport protein.

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colon cancer	DISVC52G	Definitive	Altered Expression	[1]
Colon carcinoma	DISJYKUO	Definitive	Altered Expression	[1]
Hepatocellular carcinoma	DIS0J828	Definitive	Biomarker	[2]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[3]
Acute myocardial infarction	DISE3HTG	Strong	Biomarker	[4]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[5]
Cervical cancer	DISFSHPF	Strong	Biomarker	[6]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[6]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[7]
Epilepsy	DISBB28L	Strong	Biomarker	[8]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[9]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[5]
Pulmonary fibrosis	DISQKVLA	Strong	Altered Expression	[10]
Schizophrenia	DISSRV2N	Strong	Biomarker	[8]
Thyroid gland carcinoma	DISMNGZ0	Strong	Altered Expression	[11]
Bacterial infection	DIS5QJ9S	moderate	Biomarker	[12]
Hypoglycemia	DISRCKR7	moderate	Biomarker	[13]
Stroke	DISX6UHX	moderate	Biomarker	[14]
Asthma	DISW9QNS	Limited	Altered Expression	[15]
Breast cancer	DIS7DPX1	Limited	Biomarker	[9]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[9]
Neoplasm	DISZKGEW	Limited	Biomarker	[7]

2 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 Cysteine-rich protein 1 (CRIP1).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Cysteine-rich protein 1 (CRIP1).	[30]

20 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 Cysteine-rich protein 1 (CRIP1).	[17]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Cysteine-rich protein 1 (CRIP1).	[18]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Cysteine-rich protein 1 (CRIP1).	[19]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Cysteine-rich protein 1 (CRIP1).	[20]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Cysteine-rich protein 1 (CRIP1).	[21]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Cysteine-rich protein 1 (CRIP1).	[22]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Cysteine-rich protein 1 (CRIP1).	[23]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Cysteine-rich protein 1 (CRIP1).	[24]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Cysteine-rich protein 1 (CRIP1).	[25]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Cysteine-rich protein 1 (CRIP1).	[22]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Cysteine-rich protein 1 (CRIP1).	[26]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Cysteine-rich protein 1 (CRIP1).	[27]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Cysteine-rich protein 1 (CRIP1).	[28]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Cysteine-rich protein 1 (CRIP1).	[26]
Lithium	DMZ3OU6	Phase 2	Lithium increases the expression of Cysteine-rich protein 1 (CRIP1).	[29]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Cysteine-rich protein 1 (CRIP1).	[31]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Cysteine-rich protein 1 (CRIP1).	[32]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Cysteine-rich protein 1 (CRIP1).	[33]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Cysteine-rich protein 1 (CRIP1).	[34]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine decreases the expression of Cysteine-rich protein 1 (CRIP1).	[35]

References

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• [2] C-reactive protein is an independent predictor for hepatocellular carcinoma recurrence after liver transplantation.PLoS One. 2019 May 29;14(5):e0216677. doi: 10.1371/journal.pone.0216677. eCollection 2019.
• [3] Weighted Gene Coexpression Network Analysis Identifies Cysteine-Rich Intestinal Protein 1 (CRIP1) as a Prognostic Gene Associated with Relapse in Patients with Acute Myeloid Leukemia.Med Sci Monit. 2019 Oct 2;25:7396-7406. doi: 10.12659/MSM.918092.
• [4] Selenoprotein P in Myocardial Infarction With Cardiogenic Shock.Shock. 2020 Jan;53(1):58-62. doi: 10.1097/SHK.0000000000001342.
• [5] CRIP1 expression is correlated with a favorable outcome and less metastases in osteosarcoma patients.Oncotarget. 2011 Dec;2(12):970-5. doi: 10.18632/oncotarget.398.
• [6] CRIP1 promotes cell migration, invasion and epithelial-mesenchymal transition of cervical cancer by activating the Wnt/catenin signaling pathway.Life Sci. 2018 Aug 15;207:420-427. doi: 10.1016/j.lfs.2018.05.054. Epub 2018 Jun 26.
• [7] Cysteine-rich intestinal protein 1 suppresses apoptosis and chemosensitivity to 5-fluorouracil in colorectal cancer through ubiquitin-mediated Fas degradation.J Exp Clin Cancer Res. 2019 Mar 8;38(1):120. doi: 10.1186/s13046-019-1117-z.
• [8] Cannabinoid Receptor Interacting Protein 1a (CRIP1a): Function and Structure.Molecules. 2019 Oct 12;24(20):3672. doi: 10.3390/molecules24203672.
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• [10] Cysteine-rich protein 1 is regulated by transforming growth factor-1 and expressed in lung fibrosis.J Cell Physiol. 2012 Jun;227(6):2605-12. doi: 10.1002/jcp.23000.
• [11] The Impact of Cysteine-Rich Intestinal Protein 1 (CRIP1) on Thyroid Carcinoma.Cell Physiol Biochem. 2017;43(5):2037-2046. doi: 10.1159/000484184. Epub 2017 Oct 23.
• [12] Neutralization of viral infectivity by zebrafish c-reactive protein isoforms.Mol Immunol. 2017 Nov;91:145-155. doi: 10.1016/j.molimm.2017.09.005. Epub 2017 Sep 12.
• [13] Mechanisms of action of a carbohydrate-reduced, high-protein diet in reducing the risk of postprandial hypoglycemia after Roux-en-Y gastric bypass surgery.Am J Clin Nutr. 2019 Aug 1;110(2):296-304. doi: 10.1093/ajcn/nqy310.
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• [18] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [19] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [20] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [21] 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.
• [22] 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.
• [23] 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.
• [24] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [25] Endometrial receptivity is affected in women with high circulating progesterone levels at the end of the follicular phase: a functional genomics analysis. Hum Reprod. 2011 Jul;26(7):1813-25.
• [26] 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.
• [27] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [28] Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
• [29] A genetic network model of cellular responses to lithium treatment and cocaine abuse in bipolar disorder. BMC Syst Biol. 2010 Nov 19;4:158. doi: 10.1186/1752-0509-4-158.
• [30] 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.
• [31] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [32] 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.
• [33] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.
• [34] 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.
• [35] Differential response of Mono Mac 6, BEAS-2B, and Jurkat cells to indoor dust. Environ Health Perspect. 2007 Sep;115(9):1325-32.