Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB36PHJ)

• DOT Name: Protein DEPP1 (DEPP1)
• Synonyms: Decidual protein induced by progesterone; Fasting-induced gene protein; FIG
• Gene Name: DEPP1
• Related Disease:
  Neoplasm
  Adult glioblastoma
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Colorectal carcinoma
  Fatty liver disease
  Glioblastoma multiforme
  Neuroblastoma
  Respiratory failure
  Hypoglycemia
  Endometriosis
  Gallbladder carcinoma
  Lysosomal lipid storage disorder
• UniProt ID: DEPP1_HUMAN
• Pfam ID: PF15343
• Sequence:
  MRSRLLLSVAHLPTIRETTEEMLLGGPGQEPPPSPSLDDYVRSISRLAQPTSVLDKATAQ
  GQPRPPHRPAQACRKGRPAVSLRDITARFSGQQPTLPMADTVDPLDWLFGESQEKQPSQR
  DLPRRTGPSAGLWGPHRQMDSSKPMGAPRGRLCEARMPGHSLARPPQDGQQSSDLRSWTF
  GQSAQAMASRHRPRPSSVLRTLYSHLPVIHEL
• Function: Acts as a critical modulator of FOXO3-induced autophagy via increased cellular ROS.
• Tissue Specificity: Expressed in various tissues, including pancreas, placenta, ovary, testis and kidney.

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Altered Expression	[1]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[3]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[3]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[5]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[6]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[2]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[7]
Respiratory failure	DISVMYJO	Strong	Biomarker	[8]
Hypoglycemia	DISRCKR7	moderate	Biomarker	[9]
Endometriosis	DISX1AG8	Disputed	Biomarker	[10]
Gallbladder carcinoma	DISD6ACL	Limited	Genetic Variation	[11]
Lysosomal lipid storage disorder	DISXQRTX	Limited	Biomarker	[12]

49 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 Protein DEPP1 (DEPP1).	[13]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein DEPP1 (DEPP1).	[14]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein DEPP1 (DEPP1).	[15]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Protein DEPP1 (DEPP1).	[12]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Protein DEPP1 (DEPP1).	[17]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Protein DEPP1 (DEPP1).	[18]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Protein DEPP1 (DEPP1).	[19]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Protein DEPP1 (DEPP1).	[20]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Protein DEPP1 (DEPP1).	[21]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Protein DEPP1 (DEPP1).	[21]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Protein DEPP1 (DEPP1).	[17]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Protein DEPP1 (DEPP1).	[22]
Phenobarbital	DMXZOCG	Approved	Phenobarbital increases the expression of Protein DEPP1 (DEPP1).	[12]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Protein DEPP1 (DEPP1).	[23]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Protein DEPP1 (DEPP1).	[4]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Protein DEPP1 (DEPP1).	[25]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Protein DEPP1 (DEPP1).	[26]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Protein DEPP1 (DEPP1).	[27]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of Protein DEPP1 (DEPP1).	[28]
Capsaicin	DMGMF6V	Approved	Capsaicin increases the expression of Protein DEPP1 (DEPP1).	[29]
Haloperidol	DM96SE0	Approved	Haloperidol increases the expression of Protein DEPP1 (DEPP1).	[12]
Fluoxetine	DM3PD2C	Approved	Fluoxetine increases the expression of Protein DEPP1 (DEPP1).	[27]
Sertraline	DM0FB1J	Approved	Sertraline increases the expression of Protein DEPP1 (DEPP1).	[27]
Bexarotene	DMOBIKY	Approved	Bexarotene increases the expression of Protein DEPP1 (DEPP1).	[30]
Isoniazid	DM5JVS3	Approved	Isoniazid increases the expression of Protein DEPP1 (DEPP1).	[12]
Tetracycline	DMZA017	Approved	Tetracycline increases the expression of Protein DEPP1 (DEPP1).	[12]
Thioridazine	DM35M8J	Approved	Thioridazine increases the expression of Protein DEPP1 (DEPP1).	[27]
Imipramine	DM2NUH3	Approved	Imipramine increases the expression of Protein DEPP1 (DEPP1).	[27]
Clomipramine	DMINRKW	Approved	Clomipramine increases the expression of Protein DEPP1 (DEPP1).	[27]
Erythromycin	DM4K7GQ	Approved	Erythromycin increases the expression of Protein DEPP1 (DEPP1).	[12]
Pentamidine	DMHZJCG	Approved	Pentamidine increases the expression of Protein DEPP1 (DEPP1).	[27]
Quinidine	DMLPICK	Approved	Quinidine increases the expression of Protein DEPP1 (DEPP1).	[31]
Flecainide	DMSQDLE	Approved	Flecainide increases the expression of Protein DEPP1 (DEPP1).	[27]
Perhexiline	DMINO7Z	Approved	Perhexiline increases the expression of Protein DEPP1 (DEPP1).	[27]
Ofloxacin	DM0VQN3	Approved	Ofloxacin increases the expression of Protein DEPP1 (DEPP1).	[12]
Doxepin	DMPI98T	Approved	Doxepin increases the expression of Protein DEPP1 (DEPP1).	[31]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Protein DEPP1 (DEPP1).	[32]
Fenretinide	DMRD5SP	Phase 3	Fenretinide increases the expression of Protein DEPP1 (DEPP1).	[33]
Chlorpromazine	DMBGZI3	Phase 3 Trial	Chlorpromazine increases the expression of Protein DEPP1 (DEPP1).	[27]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Protein DEPP1 (DEPP1).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Protein DEPP1 (DEPP1).	[19]
Chlorcyclizine	DM3L52Q	Phase 1	Chlorcyclizine increases the expression of Protein DEPP1 (DEPP1).	[27]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Protein DEPP1 (DEPP1).	[34]
ZIMELIDINE	DMNI3U2	Withdrawn from market	ZIMELIDINE increases the expression of Protein DEPP1 (DEPP1).	[27]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Protein DEPP1 (DEPP1).	[35]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Protein DEPP1 (DEPP1).	[36]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Protein DEPP1 (DEPP1).	[37]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Protein DEPP1 (DEPP1).	[38]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE increases the expression of Protein DEPP1 (DEPP1).	[19]

References

• [1] Baicalin induces cellular senescence in human colon cancer cells via upregulation of DEPP and the activation of Ras/Raf/MEK/ERK signaling.Cell Death Dis. 2018 Feb 13;9(2):217. doi: 10.1038/s41419-017-0223-0.
• [2] Fusion of FIG to the receptor tyrosine kinase ROS in a glioblastoma with an interstitial del(6)(q21q21).Genes Chromosomes Cancer. 2003 May;37(1):58-71. doi: 10.1002/gcc.10207.
• [3] Decreased expression of C10orf10 and its prognostic significance in human breast cancer.PLoS One. 2014 Jun 17;9(6):e99730. doi: 10.1371/journal.pone.0099730. eCollection 2014.
• [4] ERE-independent ERalpha target genes differentially expressed in human breast tumors. Mol Cell Endocrinol. 2005 Dec 21;245(1-2):53-9. doi: 10.1016/j.mce.2005.10.003. Epub 2005 Nov 17.
• [5] ALK and ROS1 overexpression is very rare in colorectal adenocarcinoma.Appl Immunohistochem Mol Morphol. 2015 Feb;23(2):134-8. doi: 10.1097/PAI.0000000000000025.
• [6] Transgenic expression of mutant peroxisome proliferator-activated receptor gamma in liver precipitates fasting-induced steatosis but protects against high-fat diet-induced steatosis in mice.Metabolism. 2005 Nov;54(11):1490-8. doi: 10.1016/j.metabol.2005.05.015.
• [7] C10ORF10/DEPP-mediated ROS accumulation is a critical modulator of FOXO3-induced autophagy.Mol Cancer. 2017 May 25;16(1):95. doi: 10.1186/s12943-017-0661-4.
• [8] Peripheral neuropathy, episodic myoglobinuria, and respiratory failure in deficiency of the mitochondrial trifunctional protein.Muscle Nerve. 2004 Jan;29(1):66-72. doi: 10.1002/mus.10500.
• [9] Growth factor signalling in the regulation of -cell fate.Diabetes Obes Metab. 2011 Oct;13 Suppl 1:21-30. doi: 10.1111/j.1463-1326.2011.01442.x.
• [10] Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
• [11] Screening for the FIG-ROS1 fusion in biliary tract carcinomas by nested PCR.Genes Chromosomes Cancer. 2014 Dec;53(12):1033-40. doi: 10.1002/gcc.22212. Epub 2014 Sep 18.
• [12] Determination of phospholipidosis potential based on gene expression analysis in HepG2 cells. Toxicol Sci. 2007 Mar;96(1):101-14.
• [13] 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.
• [14] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [15] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [16] Determination of phospholipidosis potential based on gene expression analysis in HepG2 cells. Toxicol Sci. 2007 Mar;96(1):101-14.
• [17] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [18] 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.
• [19] 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.
• [20] 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.
• [21] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [22] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [23] A novel protein Depp, which is induced by progesterone in human endometrial stromal cells activates Elk-1 transcription factor. Mol Hum Reprod. 2005 Jul;11(7):471-6. doi: 10.1093/molehr/gah186.
• [24] ERE-independent ERalpha target genes differentially expressed in human breast tumors. Mol Cell Endocrinol. 2005 Dec 21;245(1-2):53-9. doi: 10.1016/j.mce.2005.10.003. Epub 2005 Nov 17.
• [25] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [26] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [27] A toxicogenomic approach to drug-induced phospholipidosis: analysis of its induction mechanism and establishment of a novel in vitro screening system. Toxicol Sci. 2005 Feb;83(2):282-92.
• [28] Anti-inflammatory agent indomethacin reduces invasion and alters metabolism in a human breast cancer cell line. Neoplasia. 2007 Mar;9(3):222-35.
• [29] Capsaicin inhibits the migration, invasion and EMT of renal cancer cells by inducing AMPK/mTOR-mediated autophagy. Chem Biol Interact. 2022 Oct 1;366:110043. doi: 10.1016/j.cbi.2022.110043. Epub 2022 Aug 28.
• [30] 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.
• [31] In vitro detection of drug-induced phospholipidosis using gene expression and fluorescent phospholipid based methodologies. Toxicol Sci. 2007 Sep;99(1):162-73.
• [32] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [33] The transforming growth factor-beta family members bone morphogenetic protein-2 and macrophage inhibitory cytokine-1 as mediators of the antiangiogenic activity of N-(4-hydroxyphenyl)retinamide. Clin Cancer Res. 2005 Jun 15;11(12):4610-9.
• [34] 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.
• [35] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [36] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [37] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [38] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.