Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNO659U)

• DOT Name: Progestin and adipoQ receptor family member 4 (PAQR4)
• Synonyms: Progestin and adipoQ receptor family member IV
• Gene Name: PAQR4
• Related Disease:
  Breast cancer
  Breast carcinoma
  Neoplasm
  Non-small-cell lung cancer
  Prostate cancer
  Prostate neoplasm
  Gastric cancer
  Stomach cancer
• UniProt ID: PAQR4_HUMAN
• Pfam ID: PF03006
• Sequence:
  MAFLAGPRLLDWASSPPHLQFNKFVLTGYRPASSGSGCLRSLFYLHNELGNIYTHGLALL
  GFLVLVPMTMPWGQLGKDGWLGGTHCVACLAPPAGSVLYHLFMCHQGGSAVYARLLALDM
  CGVCLVNTLGALPIIHCTLACRPWLRPAALVGYTVLSGVAGWRALTAPSTSARLRAFGWQ
  AAARLLVFGARGVGLGSGAPGSLPCYLRMDALALLGGLVNVARLPERWGPGRFDYWGNSH
  QIMHLLSVGSILQLHAGVVPDLLWAAHHACPRD
• Tissue Specificity: Relatively widely expressed in a range of tissues.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Definitive	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[1]
Prostate cancer	DISF190Y	Strong	Biomarker	[2]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[2]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[3]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Progestin and adipoQ receptor family member 4 (PAQR4).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Progestin and adipoQ receptor family member 4 (PAQR4).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Progestin and adipoQ receptor family member 4 (PAQR4).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Progestin and adipoQ receptor family member 4 (PAQR4).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Progestin and adipoQ receptor family member 4 (PAQR4).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Progestin and adipoQ receptor family member 4 (PAQR4).	[9]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Progestin and adipoQ receptor family member 4 (PAQR4).	[10]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Progestin and adipoQ receptor family member 4 (PAQR4).	[11]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Progestin and adipoQ receptor family member 4 (PAQR4).	[12]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Progestin and adipoQ receptor family member 4 (PAQR4).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Progestin and adipoQ receptor family member 4 (PAQR4).	[14]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Progestin and adipoQ receptor family member 4 (PAQR4).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Progestin and adipoQ receptor family member 4 (PAQR4).	[16]

References

• [1] PAQR4 promotes cell proliferation and metastasis through the CDK4-pRB-E2F1 pathway in non-small-cell lung cancer.Onco Targets Ther. 2019 May 13;12:3625-3633. doi: 10.2147/OTT.S181432. eCollection 2019.
• [2] DNA methylome changes by estradiol benzoate and bisphenol A links early-life environmental exposures to prostate cancer risk.Epigenetics. 2016 Sep;11(9):674-689. doi: 10.1080/15592294.2016.1208891. Epub 2016 Jul 14.
• [3] MicroRNA-370 inhibits the proliferation, invasion and EMT of gastric cancer cells by directly targeting PAQR4.J Pharmacol Sci. 2018 Oct;138(2):96-106. doi: 10.1016/j.jphs.2018.08.004. Epub 2018 Aug 25.
• [4] 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.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [7] 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.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [10] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [11] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [12] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [15] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [16] 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.