Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL6QNHG)

• DOT Name: Prorelaxin H1 (RLN1)
• Gene Name: RLN1
• Related Disease:
  Prostate cancer
  Prostate carcinoma
  Coronary atherosclerosis
  Coronary heart disease
  High blood pressure
  Hyperplasia
  Prostate neoplasm
  Renal fibrosis
  Thyroid tumor
• UniProt ID: REL1_HUMAN
• Pfam ID: PF00049
• Sequence:
  MPRLFLFHLLEFCLLLNQFSRAVAAKWKDDVIKLCGRELVRAQIAICGMSTWSKRSLSQE
  DAPQTPRPVAEIVPSFINKDTETIIIMLEFIANLPPELKAALSERQPSLPELQQYVPALK
  DSNLSFEEFKKLIRNRQSEAADSNPSELKYLGLDTHSQKKRRPYVALFEKCCLIGCTKRS
  LAKYC
• Function: Relaxin is an ovarian hormone that acts with estrogen to produce dilatation of the birth canal in many mammals. May be involved in remodeling of connective tissues during pregnancy, promoting growth of pubic ligaments and ripening of the cervix.
• Tissue Specificity: Prostate. Not expressed in placenta, decidua or ovary.
• KEGG Pathway:
  Neuroactive ligand-receptor interaction (hsa04080)
  Relaxin sig.ling pathway (hsa04926)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Prostate cancer	DISF190Y	Definitive	Altered Expression	[1]
Prostate carcinoma	DISMJPLE	Definitive	Altered Expression	[1]
Coronary atherosclerosis	DISKNDYU	Strong	Altered Expression	[2]
Coronary heart disease	DIS5OIP1	Strong	Altered Expression	[2]
High blood pressure	DISY2OHH	Strong	Biomarker	[3]
Hyperplasia	DISK4DFB	Strong	Biomarker	[4]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[5]
Renal fibrosis	DISMHI3I	Strong	Biomarker	[6]
Thyroid tumor	DISLVKMD	Strong	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Prorelaxin H1 (RLN1).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Prorelaxin H1 (RLN1).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Prorelaxin H1 (RLN1).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Prorelaxin H1 (RLN1).	[10]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Prorelaxin H1 (RLN1).	[9]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Prorelaxin H1 (RLN1).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Prorelaxin H1 (RLN1).	[12]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Prorelaxin H1 (RLN1).	[11]

References

• [1] Identification of a novel fusion transcript between human relaxin-1 (RLN1) and human relaxin-2 (RLN2) in prostate cancer.Mol Cell Endocrinol. 2016 Jan 15;420:159-68. doi: 10.1016/j.mce.2015.10.011. Epub 2015 Oct 21.
• [2] Circulating Relaxin-1 Level Is a Surrogate Marker of Myocardial Fibrosis in HFrEF.Front Physiol. 2019 Jun 4;10:690. doi: 10.3389/fphys.2019.00690. eCollection 2019.
• [3] Relaxin increases cardiac output and reduces systemic arterial load in hypertensive rats.Hypertension. 2005 Oct;46(4):745-50. doi: 10.1161/01.HYP.0000184230.52059.33. Epub 2005 Sep 19.
• [4] Human medullary thyroid carcinoma: a source and potential target for relaxin-like hormones.Ann N Y Acad Sci. 2005 May;1041:449-61. doi: 10.1196/annals.1282.069.
• [5] Relaxin promotes prostate cancer progression.Clin Cancer Res. 2007 Mar 15;13(6):1695-702. doi: 10.1158/1078-0432.CCR-06-2492.
• [6] Relaxin-1-deficient mice develop an age-related progression of renal fibrosis.Kidney Int. 2004 Jun;65(6):2054-64. doi: 10.1111/j.1523-1755.2004.00628.x.
• [7] Estrogen and TCDD influence RLN2 gene activity in estrogen receptor-positive human breast cancer cells. Ann N Y Acad Sci. 2009 Apr;1160:367-73. doi: 10.1111/j.1749-6632.2009.03836.x.
• [8] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [9] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [10] 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.
• [11] 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.
• [12] 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.