Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT764FXI)

• DOT Name: Protein sprouty homolog 1 (SPRY1)
• Synonyms: Spry-1
• Gene Name: SPRY1
• UniProt ID: SPY1_HUMAN
• Pfam ID: PF05210
• Sequence:
  MDPQNQHGSGSSLVVIQQPSLDSRQRLDYEREIQPTAILSLDQIKAIRGSNEYTEGPSVV
  KRPAPRTAPRQEKHERTHEIIPINVNNNYEHRHTSHLGHAVLPSNARGPILSRSTSTGSA
  ASSGSNSSASSEQGLLGRSPPTRPVPGHRSERAIRTQPKQLIVDDLKGSLKEDLTQHKFI
  CEQCGKCKCGECTAPRTLPSCLACNRQCLCSAESMVEYGTCMCLVKGIFYHCSNDDEGDS
  YSDNPCSCSQSHCCSRYLCMGAMSLFLPCLLCYPPAKGCLKLCRRCYDWIHRPGCRCKNS
  NTVYCKLESCPSRGQGKPS
• Function: Inhibits fibroblast growth factor (FGF)-induced retinal lens fiber differentiation, probably by inhibiting FGF-mediated phosphorylation of ERK1/2. Inhibits TGFB-induced epithelial-to-mesenchymal transition in lens epithelial cells.
• Reactome Pathway: EGFR downregulation (R-HSA-182971)

Molecular Interaction Atlas (MIA) of This DOT

29 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 sprouty homolog 1 (SPRY1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein sprouty homolog 1 (SPRY1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein sprouty homolog 1 (SPRY1).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein sprouty homolog 1 (SPRY1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate affects the expression of Protein sprouty homolog 1 (SPRY1).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Protein sprouty homolog 1 (SPRY1).	[2]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Protein sprouty homolog 1 (SPRY1).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein sprouty homolog 1 (SPRY1).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Protein sprouty homolog 1 (SPRY1).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Protein sprouty homolog 1 (SPRY1).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Protein sprouty homolog 1 (SPRY1).	[10]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Protein sprouty homolog 1 (SPRY1).	[11]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Protein sprouty homolog 1 (SPRY1).	[12]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Protein sprouty homolog 1 (SPRY1).	[13]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Protein sprouty homolog 1 (SPRY1).	[14]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Protein sprouty homolog 1 (SPRY1).	[11]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of Protein sprouty homolog 1 (SPRY1).	[15]
Cidofovir	DMA13GD	Approved	Cidofovir affects the expression of Protein sprouty homolog 1 (SPRY1).	[2]
Clodronate	DM9Y6X7	Approved	Clodronate increases the expression of Protein sprouty homolog 1 (SPRY1).	[2]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Protein sprouty homolog 1 (SPRY1).	[16]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Protein sprouty homolog 1 (SPRY1).	[11]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Protein sprouty homolog 1 (SPRY1).	[17]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein sprouty homolog 1 (SPRY1).	[19]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Protein sprouty homolog 1 (SPRY1).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein sprouty homolog 1 (SPRY1).	[22]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Protein sprouty homolog 1 (SPRY1).	[23]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Protein sprouty homolog 1 (SPRY1).	[24]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Protein sprouty homolog 1 (SPRY1).	[25]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine decreases the expression of Protein sprouty homolog 1 (SPRY1).	[26]

2 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 decreases the methylation of Protein sprouty homolog 1 (SPRY1).	[18]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Protein sprouty homolog 1 (SPRY1).	[21]

References

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• [7] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
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• [9] 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.
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• [11] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [12] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [13] Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
• [14] 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.
• [15] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [16] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [17] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [18] 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.
• [19] Synergistic effect of JQ1 and rapamycin for treatment of human osteosarcoma. Int J Cancer. 2015 May 1;136(9):2055-64.
• [20] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [21] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [22] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [23] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [24] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [25] Effects of nickel treatment on H3K4 trimethylation and gene expression. PLoS One. 2011 Mar 24;6(3):e17728. doi: 10.1371/journal.pone.0017728.
• [26] Microarray Analysis of Gene Expression Alteration in Human Middle Ear Epithelial Cells Induced by Asian Sand Dust. Clin Exp Otorhinolaryngol. 2015 Dec;8(4):345-53. doi: 10.3342/ceo.2015.8.4.345. Epub 2015 Nov 10.