Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE7JIO2)

• DOT Name: Stromal cell-derived factor 2-like protein 1 (SDF2L1)
• Synonyms: SDF2-like protein 1; PWP1-interacting protein 8
• Gene Name: SDF2L1
• Related Disease:
  Fatty liver disease
  Non-insulin dependent diabetes
  Prostate cancer
  Prostate neoplasm
  Rheumatoid arthritis
  Schizophrenia
• UniProt ID: SDF2L_HUMAN
• Pfam ID: PF02815
• Sequence:
  MWSAGRGGAAWPVLLGLLLALLVPGGGAAKTGAELVTCGSVLKLLNTHHRVRLHSHDIKY
  GSGSGQQSVTGVEASDDANSYWRIRGGSEGGCPRGSPVRCGQAVRLTHVLTGKNLHTHHF
  PSPLSNNQEVSAFGEDGEGDDLDLWTVRCSGQHWEREAAVRFQHVGTSVFLSVTGEQYGS
  PIRGQHEVHGMPSANTHNTWKAMEGIFIKPSVEPSAGHDEL
• Tissue Specificity: Ubiquitously expressed with high expression in testis, moderate expression in the pancreas, spleen, prostate, small intestine and colon. Very low expression is seen in brain and skeletal muscle.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Fatty liver disease	DIS485QZ	Strong	Biomarker	[1]
Non-insulin dependent diabetes	DISK1O5Z	Strong	SusceptibilityMutation	[2]
Prostate cancer	DISF190Y	Strong	Biomarker	[3]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[3]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[4]
Schizophrenia	DISSRV2N	Strong	Biomarker	[5]

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 Stromal cell-derived factor 2-like protein 1 (SDF2L1).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Stromal cell-derived factor 2-like protein 1 (SDF2L1).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Stromal cell-derived factor 2-like protein 1 (SDF2L1).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Stromal cell-derived factor 2-like protein 1 (SDF2L1).	[9]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Stromal cell-derived factor 2-like protein 1 (SDF2L1).	[10]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Stromal cell-derived factor 2-like protein 1 (SDF2L1).	[11]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Stromal cell-derived factor 2-like protein 1 (SDF2L1).	[12]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Stromal cell-derived factor 2-like protein 1 (SDF2L1).	[13]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Stromal cell-derived factor 2-like protein 1 (SDF2L1).	[14]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Stromal cell-derived factor 2-like protein 1 (SDF2L1).	[15]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Stromal cell-derived factor 2-like protein 1 (SDF2L1).	[16]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Stromal cell-derived factor 2-like protein 1 (SDF2L1).	[17]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Stromal cell-derived factor 2-like protein 1 (SDF2L1).	[18]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of Stromal cell-derived factor 2-like protein 1 (SDF2L1).	[19]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Stromal cell-derived factor 2-like protein 1 (SDF2L1).	[20]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Stromal cell-derived factor 2-like protein 1 (SDF2L1).	[21]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Stromal cell-derived factor 2-like protein 1 (SDF2L1).	[22]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Stromal cell-derived factor 2-like protein 1 (SDF2L1).	[23]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Stromal cell-derived factor 2-like protein 1 (SDF2L1).	[24]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Stromal cell-derived factor 2-like protein 1 (SDF2L1).	[25]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Stromal cell-derived factor 2-like protein 1 (SDF2L1).	[26]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of Stromal cell-derived factor 2-like protein 1 (SDF2L1).	[11]

References

• [1] Hepatic Sdf2l1 controls feeding-induced ER stress and regulates metabolism.Nat Commun. 2019 Feb 27;10(1):947. doi: 10.1038/s41467-019-08591-6.
• [2] Three interacting genomic loci incorporating two novel mutations underlie the evolution of diet-induced diabetes.Mol Med. 2016 Oct;22:560-569. doi: 10.2119/molmed.2016.00114. Epub 2016 Jul 26.
• [3] Identification of genes potentially involved in the acquisition of androgen-independent and metastatic tumor growth in an autochthonous genetically engineered mouse prostate cancer model.Prostate. 2007 Jan 1;67(1):83-106. doi: 10.1002/pros.20505.
• [4] Studying the effects of haplotype partitioning methods on the RA-associated genomic results from the North American Rheumatoid Arthritis Consortium (NARAC) dataset.J Adv Res. 2019 Jan 18;18:113-126. doi: 10.1016/j.jare.2019.01.006. eCollection 2019 Jul.
• [5] A two-stage case-control association study of the dihydropyrimidinase-like 2 gene (DPYSL2) with schizophrenia in Japanese subjects.J Hum Genet. 2010 Jul;55(7):469-72. doi: 10.1038/jhg.2010.38. Epub 2010 Apr 23.
• [6] 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.
• [7] Inter-laboratory comparison of human renal proximal tubule (HK-2) transcriptome alterations due to Cyclosporine A exposure and medium exhaustion. Toxicol In Vitro. 2009 Apr;23(3):486-99.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [10] High-throughput ectopic expression screen for tamoxifen resistance identifies an atypical kinase that blocks autophagy. Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):2058-63.
• [11] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [12] 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.
• [13] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [14] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [15] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [16] Gene expression in endometrial cancer cells (Ishikawa) after short time high dose exposure to progesterone. Steroids. 2008 Jan;73(1):116-28.
• [17] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [18] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [19] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [20] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [21] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [22] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [23] Genome-wide gene expression profiling of low-dose, long-term exposure of human osteosarcoma cells to bisphenol A and its analogs bisphenols AF and S. Toxicol In Vitro. 2015 Aug;29(5):1060-9.
• [24] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [25] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [26] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.