Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTISDG5X)

• DOT Name: Cellular retinoic acid-binding protein 1 (CRABP1)
• Synonyms: Cellular retinoic acid-binding protein I; CRABP-I
• Gene Name: CRABP1
• Related Disease:
  Thyroid tumor
  Adenoma
  Cardiac disease
  Cardiac failure
  Clear cell renal carcinoma
  Colon cancer
  Congestive heart failure
  Endometrium adenocarcinoma
  Esophageal squamous cell carcinoma
  Head-neck squamous cell carcinoma
  Hepatitis C virus infection
  Hepatocellular carcinoma
  Keloid
  Liver cancer
  Moyamoya disease
  Neoplasm
  Neuroblastoma
  Obesity
  Papillary renal cell carcinoma
  Psoriasis
  Renal cell carcinoma
  Squamous cell carcinoma
  Thyroid gland papillary carcinoma
  Advanced cancer
  Carcinoma
  Neuroendocrine neoplasm
  Synovial sarcoma
  Breast neoplasm
  Triple negative breast cancer
  Acute myelogenous leukaemia
  Metabolic disorder
  Promyelocytic leukaemia
  Rheumatoid arthritis
• UniProt ID: RABP1_HUMAN
• PDB ID: 7A9Y; 7A9Z
• Pfam ID: PF00061
• Sequence:
  MPNFAGTWKMRSSENFDELLKALGVNAMLRKVAVAAASKPHVEIRQDGDQFYIKTSTTVR
  TTEINFKVGEGFEEETVDGRKCRSLATWENENKIHCTQTLLEGDGPKTYWTRELANDELI
  LTFGADDVVCTRIYVRE
• Function: Cytosolic CRABPs may regulate the access of retinoic acid to the nuclear retinoic acid receptors.
• Reactome Pathway: RA biosynthesis pathway (R-HSA-5365859)

Molecular Interaction Atlas (MIA) of This DOT

33 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Thyroid tumor	DISLVKMD	Definitive	Biomarker	[1]
Adenoma	DIS78ZEV	Strong	Biomarker	[2]
Cardiac disease	DISVO1I5	Strong	Biomarker	[3]
Cardiac failure	DISDC067	Strong	Biomarker	[3]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[4]
Colon cancer	DISVC52G	Strong	Genetic Variation	[5]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[3]
Endometrium adenocarcinoma	DISY6744	Strong	Altered Expression	[6]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[7]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Altered Expression	[8]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[9]
Hepatocellular carcinoma	DIS0J828	Strong	Posttranslational Modification	[10]
Keloid	DISV09JY	Strong	Biomarker	[11]
Liver cancer	DISDE4BI	Strong	Biomarker	[12]
Moyamoya disease	DISO62CA	Strong	Altered Expression	[13]
Neoplasm	DISZKGEW	Strong	Altered Expression	[14]
Neuroblastoma	DISVZBI4	Strong	Altered Expression	[15]
Obesity	DIS47Y1K	Strong	Biomarker	[16]
Papillary renal cell carcinoma	DIS25HBV	Strong	Biomarker	[4]
Psoriasis	DIS59VMN	Strong	Biomarker	[17]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[4]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[18]
Thyroid gland papillary carcinoma	DIS48YMM	Strong	Biomarker	[19]
Advanced cancer	DISAT1Z9	moderate	Altered Expression	[20]
Carcinoma	DISH9F1N	moderate	Biomarker	[21]
Neuroendocrine neoplasm	DISNPLOO	moderate	Altered Expression	[20]
Synovial sarcoma	DISEZJS7	moderate	Altered Expression	[20]
Breast neoplasm	DISNGJLM	Disputed	Altered Expression	[14]
Triple negative breast cancer	DISAMG6N	Disputed	Biomarker	[14]
Acute myelogenous leukaemia	DISCSPTN	Limited	Biomarker	[22]
Metabolic disorder	DIS71G5H	Limited	Biomarker	[16]
Promyelocytic leukaemia	DISYGG13	Limited	Altered Expression	[22]
Rheumatoid arthritis	DISTSB4J	Limited	Biomarker	[14]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Alitretinoin	DMME8LH	Approved	Cellular retinoic acid-binding protein 1 (CRABP1) decreases the response to substance of Alitretinoin.	[4]

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 Cellular retinoic acid-binding protein 1 (CRABP1).	[23]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Cellular retinoic acid-binding protein 1 (CRABP1).	[33]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cellular retinoic acid-binding protein 1 (CRABP1).	[24]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Cellular retinoic acid-binding protein 1 (CRABP1).	[25]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Cellular retinoic acid-binding protein 1 (CRABP1).	[26]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Cellular retinoic acid-binding protein 1 (CRABP1).	[27]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Cellular retinoic acid-binding protein 1 (CRABP1).	[28]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Cellular retinoic acid-binding protein 1 (CRABP1).	[25]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Cellular retinoic acid-binding protein 1 (CRABP1).	[29]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Cellular retinoic acid-binding protein 1 (CRABP1).	[30]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Cellular retinoic acid-binding protein 1 (CRABP1).	[31]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Cellular retinoic acid-binding protein 1 (CRABP1).	[32]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Cellular retinoic acid-binding protein 1 (CRABP1).	[34]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Cellular retinoic acid-binding protein 1 (CRABP1).	[35]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Cellular retinoic acid-binding protein 1 (CRABP1).	[36]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Cellular retinoic acid-binding protein 1 (CRABP1).	[37]

References

• [1] CRABP1, C1QL1 and LCN2 are biomarkers of differentiated thyroid carcinoma, and predict extrathyroidal extension.BMC Cancer. 2018 Jan 10;18(1):68. doi: 10.1186/s12885-017-3948-3.
• [2] Epigenetic profiling of synchronous colorectal neoplasias by quantitative DNA methylation analysis.Mod Pathol. 2006 Aug;19(8):1083-90. doi: 10.1038/modpathol.3800618. Epub 2006 May 12.
• [3] All-trans retinoic acid attenuates isoproterenol-induced cardiac dysfunction through Crabp1 to dampen CaMKII activation.Eur J Pharmacol. 2019 Sep 5;858:172485. doi: 10.1016/j.ejphar.2019.172485. Epub 2019 Jun 22.
• [4] Cellular retinoic acid binding protein I: expression and functional influence in renal cell carcinoma. Tumour Biol. 2005 Nov-Dec;26(6):313-23. doi: 10.1159/000089262. Epub 2005 Oct 25.
• [5] B vitamins, methionine and alcohol intake and risk of colon cancer in relation to BRAF mutation and CpG island methylator phenotype (CIMP).PLoS One. 2011;6(6):e21102. doi: 10.1371/journal.pone.0021102. Epub 2011 Jun 27.
• [6] Retinoic acid receptors and retinoid binding proteins in endometrial adenocarcinoma: differential expression of cellular retinoid binding proteins in endometrioid tumours.Int J Cancer. 1995 Aug 22;64(4):253-63. doi: 10.1002/ijc.2910640408.
• [7] Frequent methylation-associated silencing of a candidate tumor-suppressor, CRABP1, in esophageal squamous-cell carcinoma.Oncogene. 2007 Sep 27;26(44):6456-68. doi: 10.1038/sj.onc.1210459. Epub 2007 Apr 16.
• [8] The effect of cellular retinoic acid binding protein-I expression on the CYP26-mediated catabolism of all-trans retinoic acid and cell proliferation in head and neck squamous cell carcinoma.Metabolism. 2004 Aug;53(8):1007-12. doi: 10.1016/j.metabol.2003.12.015.
• [9] Regulation of Hepatitis C Virus Infection by Cellular Retinoic Acid Binding Proteins through the Modulation of Lipid Droplet Abundance.J Virol. 2019 Apr 3;93(8):e02302-18. doi: 10.1128/JVI.02302-18. Print 2019 Apr 15.
• [10] Prognostic implications of and relationship between CpG island hypermethylation and repetitive DNA hypomethylation in hepatocellular carcinoma.Clin Cancer Res. 2009 Feb 1;15(3):812-20. doi: 10.1158/1078-0432.CCR-08-0266.
• [11] Comparative proteomic analysis between normal skin and keloid scar.Br J Dermatol. 2010 Jun;162(6):1302-15. doi: 10.1111/j.1365-2133.2010.09660.x. Epub 2010 Feb 1.
• [12] Multiple genes exhibit phenobarbital-induced constitutive active/androstane receptor-mediated DNA methylation changes during liver tumorigenesis and in liver tumors.Toxicol Sci. 2009 Apr;108(2):273-89. doi: 10.1093/toxsci/kfp031. Epub 2009 Feb 20.
• [13] Elevation of CRABP-I in the cerebrospinal fluid of patients with Moyamoya disease.Stroke. 2003 Dec;34(12):2835-41. doi: 10.1161/01.STR.0000100159.43123.D7. Epub 2003 Nov 6.
• [14] CRABP1 is associated with a poor prognosis in breast cancer: adding to the complexity of breast cancer cell response to retinoic acid.Mol Cancer. 2015 Jul 5;14:129. doi: 10.1186/s12943-015-0380-7.
• [15] 9-cis-retinoic acid selectively activates the cellular retinoic acid binding protein-II gene in human neuroblastoma cells.Arch Biochem Biophys. 1995 Jun 1;319(2):457-63. doi: 10.1006/abbi.1995.1317.
• [16] Cellular retinoic acid binding protein 1 protects mice from high-fat diet-induced obesity by decreasing adipocyte hypertrophy.Int J Obes (Lond). 2020 Feb;44(2):466-474. doi: 10.1038/s41366-019-0379-z. Epub 2019 Jun 4.
• [17] Overexpression of cellular retinoic acid-binding protein type II (CRABP-II) and down-regulation of CRABP-I in psoriatic skin.Dermatology. 1992;185(4):251-6. doi: 10.1159/000247462.
• [18] Epidermal differentiation enhances CRABP II expression in human skin.J Invest Dermatol. 1994 Dec;103(6):785-90. doi: 10.1111/1523-1747.ep12413037.
• [19] TIMP1 and SERPIN-A overexpression and TFF3 and CRABP1 underexpression as biomarkers for papillary thyroid carcinoma.Head Neck. 2004 Dec;26(12):1069-83. doi: 10.1002/hed.20099.
• [20] CRABP1 provides high malignancy of transformed mesenchymal cells and contributes to the pathogenesis of mesenchymal and neuroendocrine tumors.Cell Cycle. 2014;13(10):1530-9. doi: 10.4161/cc.28475. Epub 2014 Mar 12.
• [21] DNA methylation profiling of ovarian carcinomas and their in vitro models identifies HOXA9, HOXB5, SCGB3A1, and CRABP1 as novel targets.Mol Cancer. 2007 Jul 10;6:45. doi: 10.1186/1476-4598-6-45.
• [22] RARalpha-PLZF overcomes PLZF-mediated repression of CRABPI, contributing to retinoid resistance in t(11;17) acute promyelocytic leukemia.Proc Natl Acad Sci U S A. 2007 Nov 20;104(47):18694-9. doi: 10.1073/pnas.0704433104. Epub 2007 Nov 13.
• [23] 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.
• [24] 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.
• [25] 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.
• [26] Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
• [27] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [28] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [29] Dissecting progressive stages of 5-fluorouracil resistance in vitro using RNA expression profiling. Int J Cancer. 2004 Nov 1;112(2):200-12. doi: 10.1002/ijc.20401.
• [30] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [31] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [32] 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.
• [33] 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.
• [34] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [35] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [36] 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.
• [37] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [38] Cellular retinoic acid binding protein I: expression and functional influence in renal cell carcinoma. Tumour Biol. 2005 Nov-Dec;26(6):313-23. doi: 10.1159/000089262. Epub 2005 Oct 25.