Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTJP8D4)

• DOT Name: Adipogenesis regulatory factor (ADIRF)
• Synonyms: Adipogenesis factor rich in obesity; Adipose most abundant gene transcript 2 protein; Adipose-specific protein 2; apM-2
• Gene Name: ADIRF
• Related Disease:
  Malaria
  Advanced cancer
  Prostate cancer
  Prostate carcinoma
• UniProt ID: ADIRF_HUMAN
• Sequence:
  MASKGLQDLKQQVEGTAQEAVSAAGAAAQQVVDQATEAGQKAMDQLAKTTQETIDKTANQ
  ASDTFSGIGKKFGLLK
• Function: Plays a role in fat cell development; promotes adipogenic differentiation and stimulates transcription initiation of master adipogenesis factors like PPARG and CEBPA at early stages of preadipocyte differentiation. Its overexpression confers resistance to the anticancer chemotherapeutic drug cisplatin.
• Tissue Specificity: Expressed in adipose tissue (at protein level). Highly expressed in omental and subcutaneous adipose tissues. Expressed in heart, cornea, liver, kidney and spleen.
• Reactome Pathway: Transcriptional regulation of white adipocyte differentiation (R-HSA-381340)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Malaria	DISQ9Y50	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Prostate cancer	DISF190Y	Strong	Biomarker	[3]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Adipogenesis regulatory factor (ADIRF) affects the response to substance of Methotrexate.	[21]

3 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 Adipogenesis regulatory factor (ADIRF).	[4]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Adipogenesis regulatory factor (ADIRF).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Adipogenesis regulatory factor (ADIRF).	[16]

14 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 Adipogenesis regulatory factor (ADIRF).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Adipogenesis regulatory factor (ADIRF).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Adipogenesis regulatory factor (ADIRF).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Adipogenesis regulatory factor (ADIRF).	[8]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Adipogenesis regulatory factor (ADIRF).	[10]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Adipogenesis regulatory factor (ADIRF).	[11]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Adipogenesis regulatory factor (ADIRF).	[12]
Mifepristone	DMGZQEF	Approved	Mifepristone decreases the expression of Adipogenesis regulatory factor (ADIRF).	[13]
Bexarotene	DMOBIKY	Approved	Bexarotene increases the expression of Adipogenesis regulatory factor (ADIRF).	[14]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Adipogenesis regulatory factor (ADIRF).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Adipogenesis regulatory factor (ADIRF).	[17]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Adipogenesis regulatory factor (ADIRF).	[18]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Adipogenesis regulatory factor (ADIRF).	[19]
Microcystin-LR	DMTMLRN	Investigative	Microcystin-LR increases the expression of Adipogenesis regulatory factor (ADIRF).	[20]

References

• [1] Roll Back Malaria: an historical footnote.Malar J. 2018 Nov 19;17(1):433. doi: 10.1186/s12936-018-2582-0.
• [2] APM2 is a novel mediator of cisplatin resistance in a variety of cancer cell types regardless of p53 or MMR status.Int J Cancer. 2009 Sep 1;125(5):1193-204. doi: 10.1002/ijc.24465.
• [3] C10orf116 Gene Copy Number Loss in Prostate Cancer: Clinicopathological Correlations and Prognostic Significance.Med Sci Monit. 2017 Oct 30;23:5176-5183. doi: 10.12659/msm.906680.
• [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] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [6] Effect of retinoic acid on gene expression in human conjunctival epithelium: secretory phospholipase A2 mediates retinoic acid induction of MUC16. Invest Ophthalmol Vis Sci. 2005 Nov;46(11):4050-61.
• [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] 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.
• [9] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [10] Endometrial receptivity is affected in women with high circulating progesterone levels at the end of the follicular phase: a functional genomics analysis. Hum Reprod. 2011 Jul;26(7):1813-25.
• [11] Gene expression profiling of breast cancer cells in response to gemcitabine: NF-kappaB pathway activation as a potential mechanism of resistance. Breast Cancer Res Treat. 2007 Apr;102(2):157-72.
• [12] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [13] Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
• [14] Identification of biomarkers modulated by the rexinoid LGD1069 (bexarotene) in human breast cells using oligonucleotide arrays. Cancer Res. 2006 Dec 15;66(24):12009-18.
• [15] Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
• [16] 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.
• [17] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [18] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [19] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [20] Gene expression network regulated by DNA methylation and microRNA during microcystin-leucine arginine induced malignant transformation in human hepatocyte L02 cells. Toxicol Lett. 2018 Jun 1;289:42-53. doi: 10.1016/j.toxlet.2018.03.003. Epub 2018 Mar 5.
• [21] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.