Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTECO1G8)

• DOT Name: Interferon-induced transmembrane protein 1 (IFITM1)
• Synonyms: Dispanin subfamily A member 2a; DSPA2a; Interferon-induced protein 17; Interferon-inducible protein 9-27; Leu-13 antigen; CD antigen CD225
• Gene Name: IFITM1
• Related Disease:
  Epithelial ovarian cancer
  Ovarian cancer
  Ovarian neoplasm
  Respiratory syncytial virus infection
  Adenocarcinoma
  Breast neoplasm
  Cervical cancer
  Cervical carcinoma
  Colorectal adenoma
  Colorectal neoplasm
  Esophageal squamous cell carcinoma
  Gallbladder cancer
  Gastric cancer
  Head and neck neoplasm
  Hepatitis C virus infection
  Inflammatory breast cancer
  Influenza
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Neoplasm
  Non-small-cell lung cancer
  Oral cancer
  Peutz-Jeghers syndrome
  Polyp
  Precancerous condition
  Squamous cell carcinoma
  Stomach cancer
  Ulcerative colitis
  Gastric neoplasm
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Colorectal carcinoma
  Leiomyoma
  Leiomyosarcoma
  Middle East Respiratory Syndrome (MERS)
  Neoplasm of esophagus
  Uterine fibroids
• UniProt ID: IFM1_HUMAN
• Pfam ID: PF04505
• Sequence:
  MHKEEHEVAVLGPPPSTILPRSTVINIHSETSVPDHVVWSLFNTLFLNWCCLGFIAFAYS
  VKSRDRKMVGDVTGAQAYASTAKCLNIWALILGILMTIGFILLLVFGSVTVYHIMLQIIQ
  EKRGY
• Function: IFN-induced antiviral protein which inhibits the entry of viruses to the host cell cytoplasm, permitting endocytosis, but preventing subsequent viral fusion and release of viral contents into the cytosol. Active against multiple viruses, including influenza A virus, SARS coronaviruses (SARS-CoV and SARS-CoV-2), Marburg virus (MARV), Ebola virus (EBOV), Dengue virus (DNV), West Nile virus (WNV), human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV). Can inhibit: influenza virus hemagglutinin protein-mediated viral entry, MARV and EBOV GP1,2-mediated viral entry and SARS-CoV and SARS-CoV-2 S protein-mediated viral entry. Also implicated in cell adhesion and control of cell growth and migration. Inhibits SARS-CoV-2 S protein-mediated syncytia formation. Plays a key role in the antiproliferative action of IFN-gamma either by inhibiting the ERK activation or by arresting cell growth in G1 phase in a p53-dependent manner. Acts as a positive regulator of osteoblast differentiation. In hepatocytes, IFITM proteins act in a coordinated manner to restrict HCV infection by targeting the endocytosed HCV virion for lysosomal degradation. IFITM2 and IFITM3 display anti-HCV activity that may complement the anti-HCV activity of IFITM1 by inhibiting the late stages of HCV entry, possibly in a coordinated manner by trapping the virion in the endosomal pathway and targeting it for degradation at the lysosome.
• Tissue Specificity: Bone (at protein level). Levels greatly elevated in colon cancer, cervical cancer, esophageal cancer and ovarian cancer. Expressed in glioma cell lines.
• KEGG Pathway: B cell receptor sig.ling pathway (hsa04662)
• Reactome Pathway:
  Interferon alpha/beta signaling (R-HSA-909733)
  Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)

Molecular Interaction Atlas (MIA) of This DOT

39 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Epithelial ovarian cancer	DIS56MH2	Definitive	Biomarker	[1]
Ovarian cancer	DISZJHAP	Definitive	Biomarker	[1]
Ovarian neoplasm	DISEAFTY	Definitive	Biomarker	[1]
Respiratory syncytial virus infection	DIS7FWHY	Definitive	Altered Expression	[2]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[3]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[4]
Cervical cancer	DISFSHPF	Strong	Altered Expression	[5]
Cervical carcinoma	DIST4S00	Strong	Altered Expression	[5]
Colorectal adenoma	DISTSVHM	Strong	Altered Expression	[6]
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[7]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[8]
Gallbladder cancer	DISXJUAF	Strong	Biomarker	[3]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[9]
Head and neck neoplasm	DIS1OB2G	Strong	Biomarker	[10]
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[11]
Inflammatory breast cancer	DIS3QRWA	Strong	Altered Expression	[12]
Influenza	DIS3PNU3	Strong	Altered Expression	[13]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[14]
Lung cancer	DISCM4YA	Strong	Biomarker	[15]
Lung carcinoma	DISTR26C	Strong	Biomarker	[15]
Neoplasm	DISZKGEW	Strong	Altered Expression	[16]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[17]
Oral cancer	DISLD42D	Strong	Biomarker	[10]
Peutz-Jeghers syndrome	DISF27ZJ	Strong	Altered Expression	[6]
Polyp	DISRSLYF	Strong	Biomarker	[6]
Precancerous condition	DISV06FL	Strong	Biomarker	[18]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[17]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[9]
Ulcerative colitis	DIS8K27O	Strong	Genetic Variation	[19]
Gastric neoplasm	DISOKN4Y	Disputed	Altered Expression	[20]
Advanced cancer	DISAT1Z9	Limited	Genetic Variation	[21]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[4]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[4]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[22]
Leiomyoma	DISLDDFN	Limited	Biomarker	[23]
Leiomyosarcoma	DIS6COXM	Limited	Biomarker	[23]
Middle East Respiratory Syndrome (MERS)	DIS5VPYU	Limited	Genetic Variation	[24]
Neoplasm of esophagus	DISOLKAQ	Limited	Biomarker	[25]
Uterine fibroids	DISBZRMJ	Limited	Biomarker	[23]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Interferon-induced transmembrane protein 1 (IFITM1) affects the response to substance of Etoposide.	[54]
Mitoxantrone	DMM39BF	Approved	Interferon-induced transmembrane protein 1 (IFITM1) affects the response to substance of Mitoxantrone.	[54]

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 Interferon-induced transmembrane protein 1 (IFITM1).	[26]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Interferon-induced transmembrane protein 1 (IFITM1).	[27]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Interferon-induced transmembrane protein 1 (IFITM1).	[28]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Interferon-induced transmembrane protein 1 (IFITM1).	[29]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Interferon-induced transmembrane protein 1 (IFITM1).	[30]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Interferon-induced transmembrane protein 1 (IFITM1).	[31]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Interferon-induced transmembrane protein 1 (IFITM1).	[32]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Interferon-induced transmembrane protein 1 (IFITM1).	[34]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Interferon-induced transmembrane protein 1 (IFITM1).	[35]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Interferon-induced transmembrane protein 1 (IFITM1).	[36]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Interferon-induced transmembrane protein 1 (IFITM1).	[37]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Interferon-induced transmembrane protein 1 (IFITM1).	[38]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Interferon-induced transmembrane protein 1 (IFITM1).	[31]
Selenium	DM25CGV	Approved	Selenium increases the expression of Interferon-induced transmembrane protein 1 (IFITM1).	[39]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Interferon-induced transmembrane protein 1 (IFITM1).	[40]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Interferon-induced transmembrane protein 1 (IFITM1).	[41]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Interferon-induced transmembrane protein 1 (IFITM1).	[42]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Interferon-induced transmembrane protein 1 (IFITM1).	[43]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Interferon-induced transmembrane protein 1 (IFITM1).	[44]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Interferon-induced transmembrane protein 1 (IFITM1).	[45]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Interferon-induced transmembrane protein 1 (IFITM1).	[46]
Tofacitinib	DMBS370	Approved	Tofacitinib decreases the expression of Interferon-induced transmembrane protein 1 (IFITM1).	[47]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Interferon-induced transmembrane protein 1 (IFITM1).	[41]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Interferon-induced transmembrane protein 1 (IFITM1).	[48]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol decreases the expression of Interferon-induced transmembrane protein 1 (IFITM1).	[49]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Interferon-induced transmembrane protein 1 (IFITM1).	[39]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Interferon-induced transmembrane protein 1 (IFITM1).	[51]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Interferon-induced transmembrane protein 1 (IFITM1).	[52]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Interferon-induced transmembrane protein 1 (IFITM1).	[41]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Interferon-induced transmembrane protein 1 (IFITM1).	[33]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Interferon-induced transmembrane protein 1 (IFITM1).	[50]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Interferon-induced transmembrane protein 1 (IFITM1).	[53]

References

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