Details of Drug Off-Target (DOT)

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

• DOT Name: Adipolin (C1QTNF12)
• Synonyms: Adipose-derived insulin-sensitizing factor; C1q and TNF related protein 12; Complement C1q tumor necrosis factor-related protein 12
• Gene Name: C1QTNF12
• Related Disease:
  Arteriosclerosis
  Atherosclerosis
  Cardiovascular disease
  Coronary atherosclerosis
  Coronary heart disease
  Non-insulin dependent diabetes
  Obesity
  Polycystic ovarian syndrome
  Type-1/2 diabetes
  Vascular disease
  X-linked reticulate pigmentary disorder
• UniProt ID: ADIPL_HUMAN
• Sequence:
  MRRWAWAAVVVLLGPQLVLLGGVGARREAQRTQQPGQRADPPNATASASSREGLPEAPKP
  SQASGPEFSDAHMTWLNFVRRPDDGALRKRCGSRDKKPRDLFGPPGPPGAEVTAETLLHE
  FQELLKEATERRFSGLLDPLLPQGAGLRLVGEAFHCRLQGPRRVDKRTLVELHGFQAPAA
  QGAFLRGSGLSLASGRFTAPVSGIFQFSASLHVDHSELQGKARLRARDVVCVLICIESLC
  QRHTCLEAVSGLESNSRVFTLQVQGLLQLQAGQYASVFVDNGSGAVLTIQAGSSFSGLLL
  GT
• Function: Insulin-sensitizing adipocyte-secreted protein (adipokine) that regulates glucose metabolism in liver and adipose tissue. Promotes glucose uptake in adipocytes and suppresses de novo glucose production in hepatocytes via the PI3K-Akt signaling pathway. Administration lead to reduction of blood glucose. Able to attenuate inflammation in fat tissue.
• Tissue Specificity: Predominantly expressed by adipose tissues.

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[1]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[1]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[2]
Coronary atherosclerosis	DISKNDYU	Strong	Altered Expression	[1]
Coronary heart disease	DIS5OIP1	Strong	Altered Expression	[1]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[3]
Obesity	DIS47Y1K	Strong	Altered Expression	[4]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[4]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[5]
Vascular disease	DISVS67S	Strong	Biomarker	[6]
X-linked reticulate pigmentary disorder	DIS0RB5A	Strong	Genetic Variation	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Adipolin (C1QTNF12).	[8]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Adipolin (C1QTNF12).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Adipolin (C1QTNF12).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Adipolin (C1QTNF12).	[11]

References

• [1] Decreased serum levels of CTRP12/adipolin in patients with coronary artery disease in relation to inflammatory cytokines and insulin resistance.Cytokine. 2019 Jan;113:326-331. doi: 10.1016/j.cyto.2018.09.019. Epub 2018 Oct 15.
• [2] The role of adiponectin and adipolin as anti-inflammatory adipokines in the formation of macrophage foam cells and their association with cardiovascular diseases.Clin Biochem. 2018 Apr;54:1-10. doi: 10.1016/j.clinbiochem.2018.02.008. Epub 2018 Feb 13.
• [3] Circulating C1q complement/TNF-related protein (CTRP) 1, CTRP9, CTRP12 and CTRP13 concentrations in Type 2 diabetes mellitus: In vivo regulation by glucose.PLoS One. 2017 Feb 16;12(2):e0172271. doi: 10.1371/journal.pone.0172271. eCollection 2017.
• [4] Lower circulating levels of CTRP12 and CTRP13 in polycystic ovarian syndrome: Irrespective of obesity.PLoS One. 2018 Dec 12;13(12):e0208059. doi: 10.1371/journal.pone.0208059. eCollection 2018.
• [5] The Effect of Coenzyme Q10 Supplementation on Circulating Levels of Novel Adipokine Adipolin/CTRP12 in Overweight and Obese Patients with Type 2 Diabetes.Exp Clin Endocrinol Diabetes. 2017 Mar;125(3):156-162. doi: 10.1055/s-0042-110570. Epub 2016 Sep 22.
• [6] Adipolin/CTRP12 protects against pathological vascular remodelling through suppression of smooth muscle cell growth and macrophage inflammatory response.Cardiovasc Res. 2020 Jan 1;116(1):237-249. doi: 10.1093/cvr/cvz074.
• [7] Whole exome sequencing identification of novel candidate genes in patients with proliferative diabetic retinopathy.Vision Res. 2017 Oct;139:168-176. doi: 10.1016/j.visres.2017.03.007. Epub 2017 May 9.
• [8] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [9] 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.
• [10] 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.
• [11] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.