Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFS4IKJ)

• DOT Name: Secretory carrier-associated membrane protein 1 (SCAMP1)
• Synonyms: Secretory carrier membrane protein 1
• Gene Name: SCAMP1
• Related Disease:
  Breast cancer
  Breast carcinoma
  Her2-receptor negative breast cancer
  HER2/NEU overexpressing breast cancer
  Idiopathic thrombocytopenic purpura
  Neoplasm
  Clear cell renal carcinoma
  Gallbladder cancer
  Gallbladder carcinoma
  Pancreatic cancer
  Renal cell carcinoma
• UniProt ID: SCAM1_HUMAN
• Pfam ID: PF04144
• Sequence:
  MSDFDSNPFADPDLNNPFKDPSVTQVTRNVPPGLDEYNPFSDSRTPPPGGVKMPNVPNTQ
  PAIMKPTEEHPAYTQIAKEHALAQAELLKRQEELERKAAELDRREREMQNLSQHGRKNNW
  PPLPSNFPVGPCFYQDFSVDIPVEFQKTVKLMYYLWMFHAVTLFLNIFGCLAWFCVDSAR
  AVDFGLSILWFLLFTPCSFVCWYRPLYGAFRSDSSFRFFVFFFVYICQFAVHVLQAAGFH
  NWGNCGWISSLTGLNQNIPVGIMMIIIAALFTASAVISLVMFKKVHGLYRTTGASFEKAQ
  QEFATGVMSNKTVQTAAANAASTAASSAAQNAFKGNQI
• Function: Functions in post-Golgi recycling pathways. Acts as a recycling carrier to the cell surface.
• Tissue Specificity: Widely expressed, with highest expression in brain.
• Reactome Pathway: Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Her2-receptor negative breast cancer	DISS605N	Strong	Biomarker	[1]
HER2/NEU overexpressing breast cancer	DISYKID5	Strong	Biomarker	[1]
Idiopathic thrombocytopenic purpura	DISFKGJU	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Disputed	Altered Expression	[3]
Clear cell renal carcinoma	DISBXRFJ	Limited	Biomarker	[4]
Gallbladder cancer	DISXJUAF	Limited	Biomarker	[5]
Gallbladder carcinoma	DISD6ACL	Limited	Biomarker	[5]
Pancreatic cancer	DISJC981	Limited	Altered Expression	[5]
Renal cell carcinoma	DISQZ2X8	Limited	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Secretory carrier-associated membrane protein 1 (SCAMP1).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Secretory carrier-associated membrane protein 1 (SCAMP1).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Secretory carrier-associated membrane protein 1 (SCAMP1).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Secretory carrier-associated membrane protein 1 (SCAMP1).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Secretory carrier-associated membrane protein 1 (SCAMP1).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Secretory carrier-associated membrane protein 1 (SCAMP1).	[11]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Secretory carrier-associated membrane protein 1 (SCAMP1).	[12]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Secretory carrier-associated membrane protein 1 (SCAMP1).	[13]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Secretory carrier-associated membrane protein 1 (SCAMP1).	[14]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Secretory carrier-associated membrane protein 1 (SCAMP1).	[15]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Secretory carrier-associated membrane protein 1 (SCAMP1).	[16]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Secretory carrier-associated membrane protein 1 (SCAMP1).	[7]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Secretory carrier-associated membrane protein 1 (SCAMP1).	[17]
Clodronate	DM9Y6X7	Approved	Clodronate increases the expression of Secretory carrier-associated membrane protein 1 (SCAMP1).	[7]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Secretory carrier-associated membrane protein 1 (SCAMP1).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Secretory carrier-associated membrane protein 1 (SCAMP1).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Secretory carrier-associated membrane protein 1 (SCAMP1).	[19]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Secretory carrier-associated membrane protein 1 (SCAMP1).	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Secretory carrier-associated membrane protein 1 (SCAMP1).	[20]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Secretory carrier-associated membrane protein 1 (SCAMP1).	[20]

References

• [1] MTSS1 and SCAMP1 cooperate to prevent invasion in breast cancer.Cell Death Dis. 2018 Mar 1;9(3):344. doi: 10.1038/s41419-018-0364-9.
• [2] Increasing observation rates in low-risk pediatric immune thrombocytopenia using a standardized clinical assessment and management plan (SCAMP() ).Pediatr Blood Cancer. 2017 May;64(5):10.1002/pbc.26303. doi: 10.1002/pbc.26303. Epub 2016 Oct 26.
• [3] Gene expression in early stage cervical cancer.Gynecol Oncol. 2008 Mar;108(3):520-6. doi: 10.1016/j.ygyno.2007.11.024. Epub 2008 Jan 11.
• [4] LncRNA SCAMP1 regulates ZEB1/JUN and autophagy to promote pediatric renal cell carcinoma under oxidative stress via miR-429.Biomed Pharmacother. 2019 Dec;120:109460. doi: 10.1016/j.biopha.2019.109460. Epub 2019 Sep 21.
• [5] Inhibition of SCAMP1 suppresses cell migration and invasion in human pancreatic and gallbladder cancer cells.Tumour Biol. 2013 Oct;34(5):2731-9. doi: 10.1007/s13277-013-0825-9. Epub 2013 May 8.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [7] 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.
• [8] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [11] 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.
• [12] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [13] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [14] 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.
• [15] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [16] 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.
• [17] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [18] Gene expression profiling in Caco-2 human colon cells exposed to TCDD, benzo[a]pyrene, and natural Ah receptor agonists from cruciferous vegetables and citrus fruits. Toxicol In Vitro. 2008 Mar;22(2):396-410.
• [19] 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.
• [20] 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.
• [21] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.