Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVQCO8N)

• DOT Name: Transmembrane protein 45B (TMEM45B)
• Gene Name: TMEM45B
• Related Disease:
  Benign prostatic hyperplasia
  Pancreatic cancer
  Prostate cancer
  Prostate carcinoma
  Neoplasm
  Advanced cancer
  Bone osteosarcoma
  Gastric cancer
  Lung cancer
  Lung carcinoma
  Melanoma
  Osteosarcoma
  Stomach cancer
• UniProt ID: TM45B_HUMAN
• Pfam ID: PF04819
• Sequence:
  MANFKGHALPGSFFLIIGLCWSVKYPLKYFSHTRKNSPLHYYQRLEIVEAAIRTLFSVTG
  ILAEQFVPDGPHLHLYHENHWIKLMNWQHSTMYLFFAVSGIVDMLTYLVSHVPLGVDRLV
  MAVAVFMEGFLFYYHVHNRPPLDQHIHSLLLYALFGGCVSISLEVIFRDHIVLELFRTSL
  IILQGTWFWQIGFVLFPPFGTPEWDQKDDANLMFITMCFCWHYLAALSIVAVNYSLVYCL
  LTRMKRHGRGEIIGIQKLNSDDTYQTALLSGSDEE
• Function: Plays a role in innate immunity. Mechanistically, promotes alphaviruses RNA degradation by interacting with the viral polymerase nsP4 and the mRNA-capping enzyme nsP1 and thereby interfering with the interaction between viral RNA and nsP1..

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Benign prostatic hyperplasia	DISI3CW2	Strong	Altered Expression	[1]
Pancreatic cancer	DISJC981	Strong	Biomarker	[2]
Prostate cancer	DISF190Y	Strong	Biomarker	[1]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	moderate	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[3]
Bone osteosarcoma	DIST1004	Limited	Biomarker	[4]
Gastric cancer	DISXGOUK	Limited	Biomarker	[5]
Lung cancer	DISCM4YA	Limited	Biomarker	[3]
Lung carcinoma	DISTR26C	Limited	Biomarker	[3]
Melanoma	DIS1RRCY	Limited	Altered Expression	[6]
Osteosarcoma	DISLQ7E2	Limited	Biomarker	[4]
Stomach cancer	DISKIJSX	Limited	Biomarker	[5]

2 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 Transmembrane protein 45B (TMEM45B).	[7]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Transmembrane protein 45B (TMEM45B).	[18]

15 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 Transmembrane protein 45B (TMEM45B).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate affects the expression of Transmembrane protein 45B (TMEM45B).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Transmembrane protein 45B (TMEM45B).	[10]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Transmembrane protein 45B (TMEM45B).	[11]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Transmembrane protein 45B (TMEM45B).	[12]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Transmembrane protein 45B (TMEM45B).	[13]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Transmembrane protein 45B (TMEM45B).	[14]
Cidofovir	DMA13GD	Approved	Cidofovir decreases the expression of Transmembrane protein 45B (TMEM45B).	[10]
Clodronate	DM9Y6X7	Approved	Clodronate decreases the expression of Transmembrane protein 45B (TMEM45B).	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Transmembrane protein 45B (TMEM45B).	[15]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Transmembrane protein 45B (TMEM45B).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Transmembrane protein 45B (TMEM45B).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Transmembrane protein 45B (TMEM45B).	[19]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Transmembrane protein 45B (TMEM45B).	[20]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Transmembrane protein 45B (TMEM45B).	[11]

References

• [1] TMEM45B is a novel predictive biomarker for prostate cancer progression and metastasis.Neoplasma. 2018 Sep 19;65(5):815-821. doi: 10.4149/neo_2018_170822N551. Epub 2018 Sep 4.
• [2] TMEM45B promotes proliferation, invasion and migration and inhibits apoptosis in pancreatic cancer cells.Mol Biosyst. 2016 May 24;12(6):1860-70. doi: 10.1039/c6mb00203j.
• [3] TMEM45B, up-regulated in human lung cancer, enhances tumorigenicity of lung cancer cells.Tumour Biol. 2016 Sep;37(9):12181-12191. doi: 10.1007/s13277-016-5063-5. Epub 2016 May 26.
• [4] Silencing Transmembrane Protein 45B (TNEM45B) Inhibits Proliferation, Invasion, and Tumorigenesis in Osteosarcoma Cells.Oncol Res. 2017 Jul 5;25(6):1021-1026. doi: 10.3727/096504016X14821477992177. Epub 2016 Dec 21.
• [5] Knockdown of TMEM45B inhibits cell proliferation and invasion in gastric cancer.Biomed Pharmacother. 2018 Aug;104:576-581. doi: 10.1016/j.biopha.2018.05.016. Epub 2018 May 25.
• [6] Identification of a gene signature for discriminating metastatic from primary melanoma using a molecular interaction network approach.Sci Rep. 2017 Dec 11;7(1):17314. doi: 10.1038/s41598-017-17330-0.
• [7] 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.
• [8] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] 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.
• [11] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [12] 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.
• [13] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [14] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [15] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [16] 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.
• [17] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [18] 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.
• [19] Involvement of the Endocrine-Disrupting Chemical Bisphenol A (BPA) in Human Placentation. J Clin Med. 2020 Feb 3;9(2):405. doi: 10.3390/jcm9020405.
• [20] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.