Details of Drug Off-Target (DOT)

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

• DOT Name: Protein LRATD2 (LRATD2)
• Synonyms: Breast cancer membrane protein 101; LRAT domain-containing 2; Protein FAM84B; Protein NSE2
• Gene Name: LRATD2
• Related Disease:
  Carcinoma of esophagus
  Esophageal cancer
  Neoplasm of esophagus
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Esophageal squamous cell carcinoma
  Gastric cancer
  Prostate cancer
  Prostate carcinoma
  Stomach cancer
  Carcinoma
  Neoplasm
• UniProt ID: LRAT2_HUMAN
• Pfam ID: PF04970
• Sequence:
  MGNQVEKLTHLSYKEVPTADPTGVDRDDGPRIGVSYIFSNDDEDVEPQPPPQGPDGGGLP
  DGGDGPPPPQPQPYDPRLHEVECSVFYRDECIYQKSFAPGSAALSTYTPENLLNKCKPGD
  LVEFVSQAQYPHWAVYVGNFQVVHLHRLEVINSFLTDASQGRRGRVVNDLYRYKPLSSSA
  VVRNALAHVGAKERELSWRNSESFAAWCRYGKREFKIGGELRIGKQPYRLQIQLSAQRSH
  TLEFQSLEDLIMEKRRNDQIGRAAVLQELATHLHPAEPEEGDSNVARTTPPPGRPPAPSS
  EEEDGEAVAH
• Tissue Specificity: Expressed in esophageal squamous cell carcinomas.

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma of esophagus	DISS6G4D	Definitive	Biomarker	[1]
Esophageal cancer	DISGB2VN	Definitive	Biomarker	[1]
Neoplasm of esophagus	DISOLKAQ	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[3]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[3]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[4]
Gastric cancer	DISXGOUK	Strong	Biomarker	[2]
Prostate cancer	DISF190Y	Strong	Biomarker	[5]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[5]
Stomach cancer	DISKIJSX	Strong	Biomarker	[2]
Carcinoma	DISH9F1N	moderate	Altered Expression	[6]
Neoplasm	DISZKGEW	moderate	Altered Expression	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Protein LRATD2 (LRATD2).	[7]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein LRATD2 (LRATD2).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein LRATD2 (LRATD2).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Protein LRATD2 (LRATD2).	[10]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Protein LRATD2 (LRATD2).	[8]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Protein LRATD2 (LRATD2).	[11]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein LRATD2 (LRATD2).	[12]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Protein LRATD2 (LRATD2).	[13]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Protein LRATD2 (LRATD2).	[14]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Protein LRATD2 (LRATD2).	[15]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Protein LRATD2 (LRATD2).	[16]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Protein LRATD2 (LRATD2).	[17]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of Protein LRATD2 (LRATD2).	[8]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Protein LRATD2 (LRATD2).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Protein LRATD2 (LRATD2).	[18]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Protein LRATD2 (LRATD2).	[19]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Protein LRATD2 (LRATD2).	[20]

References

• [1] Negative implication of C-MYC as an amplification target in esophageal cancer.Cancer Genet Cytogenet. 2006 Feb;165(1):20-4. doi: 10.1016/j.cancergencyto.2005.07.009.
• [2] Long non-coding RNA FAM84B-AS promotes resistance of gastric cancer to platinum drugs through inhibition of FAM84B expression.Biochem Biophys Res Commun. 2019 Feb 12;509(3):753-762. doi: 10.1016/j.bbrc.2018.12.177. Epub 2019 Jan 9.
• [3] Deletion of the murine ortholog of the 8q24 gene desert has anti-cancer effects in transgenic mammary cancer models.BMC Cancer. 2018 Dec 10;18(1):1233. doi: 10.1186/s12885-018-5109-8.
• [4] Genomic analyses reveal FAM84B and the NOTCH pathway are associated with the progression of esophageal squamous cell carcinoma.Gigascience. 2016 Jan 11;5:1. doi: 10.1186/s13742-015-0107-0. eCollection 2016.
• [5] FAM84B promotes prostate tumorigenesis through a network alteration.Ther Adv Med Oncol. 2019 May 13;11:1758835919846372. doi: 10.1177/1758835919846372. eCollection 2019.
• [6] Upregulation of FAM84B during prostate cancer progression.Oncotarget. 2017 Mar 21;8(12):19218-19235. doi: 10.18632/oncotarget.15168.
• [7] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [8] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [14] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [15] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [16] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [17] Gene expression signatures after ethanol exposure in differentiating embryoid bodies. Toxicol In Vitro. 2018 Feb;46:66-76.
• [18] 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.
• [19] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [20] Analysis of the prostate cancer cell line LNCaP transcriptome using a sequencing-by-synthesis approach. BMC Genomics. 2006 Sep 29;7:246. doi: 10.1186/1471-2164-7-246.