Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT65ZFZN)

• DOT Name: Adiponectin receptor protein 1 (ADIPOR1)
• Synonyms: Progestin and adipoQ receptor family member 1; Progestin and adipoQ receptor family member I
• Gene Name: ADIPOR1
• Related Disease:
  Arteriosclerosis
  Atherosclerosis
  Acute myelogenous leukaemia
  Advanced cancer
  Alzheimer disease
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Chronic obstructive pulmonary disease
  Chronic renal failure
  Colon cancer
  Colon carcinoma
  Congestive heart failure
  Coronary heart disease
  End-stage renal disease
  Epithelial ovarian cancer
  Gastric cancer
  Glioblastoma multiforme
  Glioma
  Hepatocellular carcinoma
  High blood pressure
  Hyperglycemia
  Hyperinsulinemia
  Non-alcoholic fatty liver disease
  Non-insulin dependent diabetes
  Non-small-cell lung cancer
  Obesity
  Osteoarthritis
  Ovarian neoplasm
  Pheochromocytoma
  Polycystic ovarian syndrome
  Rheumatoid arthritis
  Stomach cancer
  Diabetic kidney disease
  Female infertility
  Lung cancer
  Lung carcinoma
  Adenocarcinoma
  Colitis
  Coronary atherosclerosis
  Endometrial cancer
  Endometrial carcinoma
  Fatty liver disease
  Fetal growth restriction
  Metabolic disorder
  Retinitis pigmentosa
  Type-1 diabetes
• UniProt ID: PAQR1_HUMAN
• PDB ID: 5LXG; 6KRZ; 6KS0
• Pfam ID: PF03006
• Sequence:
  MSSHKGSVVAQGNGAPASNREADTVELAELGPLLEEKGKRVIANPPKAEEEQTCPVPQEE
  EEEVRVLTLPLQAHHAMEKMEEFVYKVWEGRWRVIPYDVLPDWLKDNDYLLHGHRPPMPS
  FRACFKSIFRIHTETGNIWTHLLGFVLFLFLGILTMLRPNMYFMAPLQEKVVFGMFFLGA
  VLCLSFSWLFHTVYCHSEKVSRTFSKLDYSGIALLIMGSFVPWLYYSFYCSPQPRLIYLS
  IVCVLGISAIIVAQWDRFATPKHRQTRAGVFLGLGLSGVVPTMHFTIAEGFVKATTVGQM
  GWFFLMAVMYITGAGLYAARIPERFFPGKFDIWFQSHQIFHVLVVAAAFVHFYGVSNLQE
  FRYGLEGGCTDDTLL
• Function: Receptor for ADIPOQ, an essential hormone secreted by adipocytes that regulates glucose and lipid metabolism. Required for normal glucose and fat homeostasis and for maintaining a normal body weight. ADIPOQ-binding activates a signaling cascade that leads to increased AMPK activity, and ultimately to increased fatty acid oxidation, increased glucose uptake and decreased gluconeogenesis. Has high affinity for globular adiponectin and low affinity for full-length adiponectin.
• Tissue Specificity: Widely expressed . Highly expressed in heart and skeletal muscle . Expressed at intermediate level in brain, spleen, kidney, liver, placenta, lung and peripheral blood leukocytes . Weakly expressed in colon, thymus and small intestine .
• KEGG Pathway:
  AMPK sig.ling pathway (hsa04152)
  Longevity regulating pathway (hsa04211)
  Adipocytokine sig.ling pathway (hsa04920)
  Non-alcoholic fatty liver disease (hsa04932)
  Alcoholic liver disease (hsa04936)
• Reactome Pathway: AMPK inhibits chREBP transcriptional activation activity (R-HSA-163680)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arteriosclerosis	DISK5QGC	Definitive	Altered Expression	[1]
Atherosclerosis	DISMN9J3	Definitive	Altered Expression	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[5]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[5]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Genetic Variation	[6]
Chronic renal failure	DISGG7K6	Strong	Biomarker	[7]
Colon cancer	DISVC52G	Strong	Genetic Variation	[8]
Colon carcinoma	DISJYKUO	Strong	Genetic Variation	[8]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[9]
Coronary heart disease	DIS5OIP1	Strong	Genetic Variation	[10]
End-stage renal disease	DISXA7GG	Strong	Biomarker	[7]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[11]
Gastric cancer	DISXGOUK	Strong	Genetic Variation	[12]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[13]
Glioma	DIS5RPEH	Strong	Biomarker	[14]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[15]
High blood pressure	DISY2OHH	Strong	Biomarker	[16]
Hyperglycemia	DIS0BZB5	Strong	Biomarker	[17]
Hyperinsulinemia	DISIDWT6	Strong	Altered Expression	[18]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Altered Expression	[19]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Altered Expression	[20]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[21]
Obesity	DIS47Y1K	Strong	Altered Expression	[22]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[23]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[24]
Pheochromocytoma	DIS56IFV	Strong	Altered Expression	[25]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Altered Expression	[26]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[23]
Stomach cancer	DISKIJSX	Strong	Genetic Variation	[12]
Diabetic kidney disease	DISJMWEY	moderate	Biomarker	[27]
Female infertility	DIS9GNYZ	moderate	Biomarker	[28]
Lung cancer	DISCM4YA	moderate	Altered Expression	[29]
Lung carcinoma	DISTR26C	moderate	Altered Expression	[29]
Adenocarcinoma	DIS3IHTY	Disputed	Altered Expression	[30]
Colitis	DISAF7DD	Limited	Biomarker	[31]
Coronary atherosclerosis	DISKNDYU	Limited	Altered Expression	[32]
Endometrial cancer	DISW0LMR	Limited	Biomarker	[33]
Endometrial carcinoma	DISXR5CY	Limited	Biomarker	[33]
Fatty liver disease	DIS485QZ	Limited	Biomarker	[34]
Fetal growth restriction	DIS5WEJ5	Limited	Therapeutic	[35]
Metabolic disorder	DIS71G5H	Limited	Genetic Variation	[10]
Retinitis pigmentosa	DISCGPY8	Limited	Autosomal dominant	[36]
Type-1 diabetes	DIS7HLUB	Limited	Biomarker	[37]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Adiponectin receptor protein 1 (ADIPOR1) affects the response to substance of Acetaminophen.	[48]

10 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 Adiponectin receptor protein 1 (ADIPOR1).	[38]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Adiponectin receptor protein 1 (ADIPOR1).	[39]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Adiponectin receptor protein 1 (ADIPOR1).	[40]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Adiponectin receptor protein 1 (ADIPOR1).	[41]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Adiponectin receptor protein 1 (ADIPOR1).	[42]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone affects the expression of Adiponectin receptor protein 1 (ADIPOR1).	[43]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Adiponectin receptor protein 1 (ADIPOR1).	[44]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Adiponectin receptor protein 1 (ADIPOR1).	[46]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Adiponectin receptor protein 1 (ADIPOR1).	[47]
25-hydroxycholesterol	DMCHAQ7	Investigative	25-hydroxycholesterol decreases the expression of Adiponectin receptor protein 1 (ADIPOR1).	[42]

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 Adiponectin receptor protein 1 (ADIPOR1).	[45]

References

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• [5] Effects of two types of energy restriction on methylation levels of adiponectin receptor 1 and leptin receptor overlapping transcript in a mouse mammary tumour virus-transforming growth factor- breast cancer mouse model.Br J Nutr. 2021 Jan 14;125(1):1-9. doi: 10.1017/S0007114519002757. Epub 2019 Nov 5.
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• [8] Effects of genetic variations in the adiponectin pathway genes on the risk of colorectal cancer in the Chinese population.BMC Med Genet. 2011 Jul 12;12:94. doi: 10.1186/1471-2350-12-94.
• [9] MicroRNA-150 inhibits expression of adiponectin receptor 2 and is a potential therapeutic target in patients with chronic heart failure.J Heart Lung Transplant. 2014 Mar;33(3):252-60. doi: 10.1016/j.healun.2013.10.014. Epub 2013 Oct 12.
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• [12] Association of variants on ADIPOQ and AdipoR1 and the prognosis of gastric cancer patients after gastrectomy treatment.Mol Biol Rep. 2015 Feb;42(2):355-61. doi: 10.1007/s11033-014-3775-4. Epub 2014 Oct 1.
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• [15] MiR-221 mediates the epithelial-mesenchymal transition of hepatocellular carcinoma by targeting AdipoR1.Int J Biol Macromol. 2017 Oct;103:1054-1061. doi: 10.1016/j.ijbiomac.2017.05.108. Epub 2017 May 21.
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• [17] Adiponectin receptor-mediated signaling ameliorates cerebral cell damage and regulates the neurogenesis of neural stem cells at high glucose concentrations: an in vivo and in vitro study.Cell Death Dis. 2015 Aug 6;6(8):e1844. doi: 10.1038/cddis.2015.220.
• [18] Adiponectin effects and gene expression in rainbow trout: an in vivo and in vitro approach.J Exp Biol. 2012 Apr 15;215(Pt 8):1373-83. doi: 10.1242/jeb.061697.
• [19] Moderate consumption of fermented alcoholic beverages diminishes diet-induced non-alcoholic fatty liver disease through mechanisms involving hepatic adiponectin signaling in mice.Eur J Nutr. 2020 Mar;59(2):787-799. doi: 10.1007/s00394-019-01945-2. Epub 2019 Mar 16.
• [20] The Effects of Adiponectin and Adiponectin Receptor 1 Levels on Macrovascular Complications Among Patients with Type 2 Diabetes Mellitus.Cell Physiol Biochem. 2019;52(2):225-231. doi: 10.33594/000000016. Epub 2019 Feb 28.
• [21] Adiponectin inhibits migration and invasion by reversing epithelialmesenchymal transition in nonsmall cell lung carcinoma.Oncol Rep. 2018 Sep;40(3):1330-1338. doi: 10.3892/or.2018.6523. Epub 2018 Jun 25.
• [22] Maternal obesity influences expression and DNA methylation of the adiponectin and leptin systems in human third-trimester placenta.Clin Epigenetics. 2019 Feb 7;11(1):20. doi: 10.1186/s13148-019-0612-6.
• [23] Adiponectin receptor 1 mediates the difference in adiponectin- induced prostaglandin E2 production in rheumatoid arthritis and osteoarthritis synovial fibroblasts.Chin Med J (Engl). 2011 Dec;124(23):3919-24.
• [24] Expression of adiponectin and its receptors is altered in epithelial ovarian tumors and ascites-derived ovarian cancer cell lines.Int J Gynecol Cancer. 2015 Mar;25(3):399-406. doi: 10.1097/IGC.0000000000000369.
• [25] Expression of adiponectin receptors 1 and 2 and the leptin receptor in human adrenal tumors.Arch Med Sci. 2019 Sep;15(5):1254-1260. doi: 10.5114/aoms.2018.76142. Epub 2018 Jun 1.
• [26] The phytoestrogen, quercetin, in serum, uterus and ovary as a potential treatment for dehydroepiandrosterone-induced polycystic ovary syndrome in the rat.Reprod Fertil Dev. 2020 Feb;32(3):313-321. doi: 10.1071/RD19072.
• [27] Telmisartan attenuates diabetic nephropathy progression by inhibiting the dimerization of angiotensin type-1 receptor and adiponectin receptor-1.Life Sci. 2019 Mar 15;221:109-120. doi: 10.1016/j.lfs.2019.01.044. Epub 2019 Jan 27.
• [28] Adiponectin and leptin systems in human endometrium during window of implantation.Fertil Steril. 2012 Mar;97(3):771-8.e1. doi: 10.1016/j.fertnstert.2011.12.042. Epub 2012 Jan 21.
• [29] Single nucleotide polymorphisms in VTI1A gene contribute to the susceptibility of Chinese population to non-small cell lung cancer.Int J Biol Markers. 2015 Jul 22;30(3):e286-93. doi: 10.5301/jbm.5000140.
• [30] Adiponectin and adiponectin receptor in relation to colorectal cancer progression.Int J Cancer. 2010 Dec 15;127(12):2758-67. doi: 10.1002/ijc.25301.
• [31] Adiponectin confers protection from acute colitis and restricts a B cell immune response.J Biol Chem. 2017 Apr 21;292(16):6569-6582. doi: 10.1074/jbc.M115.712646. Epub 2017 Mar 3.
• [32] Are decreased AdipoR1 mRNA levels associated with adiponectin resistance in coronary artery disease patients?.Clin Exp Pharmacol Physiol. 2015 Apr;42(4):331-6. doi: 10.1111/1440-1681.12361.
• [33] Acrp30 inhibits leptin-induced metastasis by downregulating the JAK/STAT3 pathway via AMPK activation in aggressive SPEC-2 endometrial cancer cells.Oncol Rep. 2012 May;27(5):1488-96. doi: 10.3892/or.2012.1670. Epub 2012 Feb 2.
• [34] Enhanced adiponectin actions by overexpression of adiponectin receptor 1 in macrophages.Atherosclerosis. 2013 May;228(1):124-35. doi: 10.1016/j.atherosclerosis.2013.02.026. Epub 2013 Mar 4.
• [35] Maternal docosahexaenoic acid increases adiponectin and normalizes IUGR-induced changes in rat adipose deposition.J Obes. 2013;2013:312153. doi: 10.1155/2013/312153. Epub 2013 Mar 6.
• [36] A mutation in ADIPOR1 causes nonsyndromic autosomal dominant retinitis pigmentosa. Hum Genet. 2016 Dec;135(12):1375-1387. doi: 10.1007/s00439-016-1730-2. Epub 2016 Sep 21.
• [37] Therapeutic window of globular adiponectin against cerebral ischemia in diabetic mice: the role of dynamic alteration of adiponectin/adiponectin receptor expression.Sci Rep. 2015 Nov 27;5:17310. doi: 10.1038/srep17310.
• [38] 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.
• [39] Transcriptome responses in blood reveal distinct biological pathways associated with arsenic exposure through drinking water in rural settings of Punjab, Pakistan. Environ Int. 2020 Feb;135:105403. doi: 10.1016/j.envint.2019.105403. Epub 2019 Dec 18.
• [40] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [41] Adiponectin Reverses the Proliferative Effects of Estradiol and IGF-1 in Human Epithelial Ovarian Cancer Cells by Downregulating the Expression of Their Receptors. Horm Cancer. 2018 Jun;9(3):166-174. doi: 10.1007/s12672-018-0331-z. Epub 2018 Mar 30.
• [42] Regulation of adiponectin receptor 1 in human hepatocytes by agonists of nuclear receptors. Biochem Biophys Res Commun. 2005 Sep 2;334(3):924-9. doi: 10.1016/j.bbrc.2005.06.187.
• [43] Changes in adiponectin receptor expression in muscle and adipose tissue of type 2 diabetic patients during rosiglitazone therapy. Diabetologia. 2005 Aug;48(8):1585-9. doi: 10.1007/s00125-005-1835-y. Epub 2005 Jul 1.
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• [47] Adiponectin attenuates lung fibroblasts activation and pulmonary fibrosis induced by paraquat. PLoS One. 2015 May 6;10(5):e0125169. doi: 10.1371/journal.pone.0125169. eCollection 2015.
• [48] Interindividual variation in gene expression responses and metabolite formation in acetaminophen-exposed primary human hepatocytes. Arch Toxicol. 2016 May;90(5):1103-15. doi: 10.1007/s00204-015-1545-2. Epub 2015 Jun 24.