Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDNK7EX)

• DOT Name: Prostate androgen-regulated mucin-like protein 1 (PARM1)
• Synonyms: PARM-1
• Gene Name: PARM1
• Related Disease:
  Colorectal carcinoma
  Crohn disease
  Neoplasm
  Nephrotic syndrome
  Prostate cancer
  Prostate carcinoma
• UniProt ID: PARM1_HUMAN
• Pfam ID: PF17061
• Sequence:
  MVYKTLFALCILTAGWRVQSLPTSAPLSVSLPTNIVPPTTIWTSSPQNTDADTASPSNGT
  HNNSVLPVTASAPTSLLPKNISIESREEEITSPGSNWEGTNTDPSPSGFSSTSGGVHLTT
  TLEEHSSGTPEAGVAATLSQSAAEPPTLISPQAPASSPSSLSTSPPEVFSASVTTNHSST
  VTSTQPTGAPTAPESPTEESSSDHTPTSHATAEPVPQEKTPPTTVSGKVMCELIDMETTT
  TFPRVIMQEVEHALSSGSIAAITVTVIAVVLLVFGVAAYLKIRHSSYGRLLDDHDYGSWG
  NYNNPLYDDS
• Function: May regulate TLP1 expression and telomerase activity, thus enabling certain prostatic cells to resist apoptosis.
• Tissue Specificity: Widely expressed with highest levels in heart, kidney and placenta.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[1]
Crohn disease	DIS2C5Q8	Strong	Genetic Variation	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Nephrotic syndrome	DISSPSC2	Strong	Genetic Variation	[3]
Prostate cancer	DISF190Y	Strong	Biomarker	[4]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Prostate androgen-regulated mucin-like protein 1 (PARM1).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Prostate androgen-regulated mucin-like protein 1 (PARM1).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Prostate androgen-regulated mucin-like protein 1 (PARM1).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Prostate androgen-regulated mucin-like protein 1 (PARM1).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Prostate androgen-regulated mucin-like protein 1 (PARM1).	[9]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Prostate androgen-regulated mucin-like protein 1 (PARM1).	[10]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Prostate androgen-regulated mucin-like protein 1 (PARM1).	[11]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Prostate androgen-regulated mucin-like protein 1 (PARM1).	[12]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Prostate androgen-regulated mucin-like protein 1 (PARM1).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Prostate androgen-regulated mucin-like protein 1 (PARM1).	[15]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Prostate androgen-regulated mucin-like protein 1 (PARM1).	[16]

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 increases the methylation of Prostate androgen-regulated mucin-like protein 1 (PARM1).	[14]

References

• [1] Neurexophilin and PC-esterase domain family member 4 (NXPE4) and prostate androgen-regulated mucin-like protein 1 (PARM1) as prognostic biomarkers for colorectal cancer.J Cell Biochem. 2019 Oct;120(10):18041-18052. doi: 10.1002/jcb.29107. Epub 2019 Jul 11.
• [2] Genetic susceptibility to inflammation and colonic transit in lower functional gastrointestinal disorders: preliminary analysis.Neurogastroenterol Motil. 2011 Oct;23(10):935-e398. doi: 10.1111/j.1365-2982.2011.01749.x. Epub 2011 Jul 14.
• [3] Genetic Identification of Two Novel Loci Associated with Steroid-Sensitive Nephrotic Syndrome.J Am Soc Nephrol. 2019 Aug;30(8):1375-1384. doi: 10.1681/ASN.2018101054. Epub 2019 Jul 1.
• [4] Human PARM-1 is a novel mucin-like, androgen-regulated gene exhibiting proliferative effects in prostate cancer cells.Int J Cancer. 2008 Mar 15;122(6):1229-35. doi: 10.1002/ijc.23185.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] 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.
• [7] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [8] 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.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] Persistent and non-persistent changes in gene expression result from long-term estrogen exposure of MCF-7 breast cancer cells. J Steroid Biochem Mol Biol. 2011 Feb;123(3-5):140-50.
• [11] 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.
• [12] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [13] 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.
• [14] 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.
• [15] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [16] Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.