Details of Drug Off-Target (DOT)

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

• DOT Name: Talin rod domain-containing protein 1 (TLNRD1)
• Synonyms: Mesoderm development candidate 1
• Gene Name: TLNRD1
• Related Disease:
  Bladder cancer
  Hepatocellular carcinoma
  Urinary bladder cancer
  Urinary bladder neoplasm
  Neoplasm
• UniProt ID: TLRN1_HUMAN
• PDB ID: 6XZ3; 6XZ4
• Sequence:
  MASGSAGKPTGEAASPAPASAIGGASSQPRKRLVSVCDHCKGKMQLVADLLLLSSEARPV
  LFEGPASSGAGAESFEQCRDTIIARTKGLSILTHDVQSQLNMGRFGEAGDSLVELGDLVV
  SLTECSAHAAYLAAVATPGAQPAQPGLVDRYRVTRCRHEVEQGCAVLRATPLADMTPQLL
  LEVSQGLSRNLKFLTDACALASDKSRDRFSREQFKLGVKCMSTSASALLACVREVKVAPS
  ELARSRCALFSGPLVQAVSALVGFATEPQFLGRAAAVSAEGKAVQTAILGGAMSVVSACV
  LLTQCLRDLAQHPDGGAKMSDHRERLRNSACAVSEGCTLLSQALRERSSPRTLPPVNSNS
  VN
• Function: Actin-binding protein which may have an oncogenic function and regulates cell proliferation, migration and invasion in cancer cells.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bladder cancer	DISUHNM0	Strong	Altered Expression	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[2]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[1]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	moderate	Biomarker	[2]

1 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 Talin rod domain-containing protein 1 (TLNRD1).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Talin rod domain-containing protein 1 (TLNRD1).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Talin rod domain-containing protein 1 (TLNRD1).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Talin rod domain-containing protein 1 (TLNRD1).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Talin rod domain-containing protein 1 (TLNRD1).	[7]
Melphalan	DMOLNHF	Approved	Melphalan increases the expression of Talin rod domain-containing protein 1 (TLNRD1).	[8]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Talin rod domain-containing protein 1 (TLNRD1).	[9]
APR-246	DMNFADH	Phase 2	APR-246 affects the expression of Talin rod domain-containing protein 1 (TLNRD1).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Talin rod domain-containing protein 1 (TLNRD1).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Talin rod domain-containing protein 1 (TLNRD1).	[12]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Talin rod domain-containing protein 1 (TLNRD1).	[13]

References

• [1] Novel oncogenic function of mesoderm development candidate 1 and its regulation by MiR-574-3p in bladder cancer cell lines.Int J Oncol. 2012 Apr;40(4):951-9. doi: 10.3892/ijo.2011.1294. Epub 2011 Dec 13.
• [2] miR-508-5p acts as an anti-oncogene by targeting MESDC1 in hepatocellular carcinoma.Neoplasma. 2017;64(1):40-47. doi: 10.4149/neo_2017_105.
• [3] 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.
• [4] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [5] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [6] 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.
• [7] 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.
• [8] Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] Mutant p53 reactivation by PRIMA-1MET induces multiple signaling pathways converging on apoptosis. Oncogene. 2010 Mar 4;29(9):1329-38. doi: 10.1038/onc.2009.425. Epub 2009 Nov 30.
• [11] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [12] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [13] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.