Details of Drug Off-Target (DOT)

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

• DOT Name: Interferon-induced protein 44 (IFI44)
• Synonyms: p44; Microtubule-associated protein 44
• Gene Name: IFI44
• Related Disease:
  Lung neoplasm
  Advanced cancer
  Benign prostatic hyperplasia
  Breast cancer
  Breast carcinoma
  Ductal breast carcinoma in situ
  Hepatitis C virus infection
  HIV infectious disease
  Influenza
  Liposarcoma
  Neoplasm of testis
  Non-small-cell lung cancer
  Prostate cancer
  Prostate carcinoma
  Seminoma
  Systemic lupus erythematosus
  Chronic graft versus host disease
  Lupus nephritis
  Colitis
  Rheumatoid arthritis
  Trichothiodystrophy
  Xeroderma pigmentosum
• UniProt ID: IFI44_HUMAN
• Sequence:
  MAVTTRLTWLHEKILQNHFGGKRLSLLYKGSVHGFRNGVLLDRCCNQGPTLTVIYSEDHI
  IGAYAEESYQEGKYASIILFALQDTKISEWKLGLCTPETLFCCDVTKYNSPTNFQIDGRN
  RKVIMDLKTMENLGLAQNCTISIQDYEVFRCEDSLDERKIKGVIELRKSLLSALRTYEPY
  GSLVQQIRILLLGPIGAGKSSFFNSVRSVFQGHVTHQALVGTNTTGISEKYRTYSIRDGK
  DGKYLPFILCDSLGLSEKEGGLCRDDIFYILNGNIRDRYQFNPMESIKLNHHDYIDSPSL
  KDRIHCVAFVFDASSIQYFSSQMIVKIKRIRRELVNAGVVHVALLTHVDSMDLITKGDLI
  EIERCEPVRSKLEEVQRKLGFALSDISVVSNYSSEWELDPVKDVLILSALRRMLWAADDF
  LEDLPFEQIGNLREEIINCAQGKK
• Function: This protein aggregates to form microtubular structures.

Molecular Interaction Atlas (MIA) of This DOT

22 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung neoplasm	DISVARNB	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Benign prostatic hyperplasia	DISI3CW2	Strong	Genetic Variation	[3]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[4]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[4]
Ductal breast carcinoma in situ	DISLCJY7	Strong	Biomarker	[4]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[5]
HIV infectious disease	DISO97HC	Strong	Biomarker	[6]
Influenza	DIS3PNU3	Strong	Biomarker	[7]
Liposarcoma	DIS8IZVM	Strong	Genetic Variation	[8]
Neoplasm of testis	DISK4XHT	Strong	Altered Expression	[9]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[10]
Prostate cancer	DISF190Y	Strong	Altered Expression	[1]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[1]
Seminoma	DIS3J8LJ	Strong	Altered Expression	[9]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[11]
Chronic graft versus host disease	DIS1MM9J	moderate	Biomarker	[12]
Lupus nephritis	DISCVGPZ	moderate	Altered Expression	[13]
Colitis	DISAF7DD	Limited	Biomarker	[14]
Rheumatoid arthritis	DISTSB4J	Limited	Altered Expression	[15]
Trichothiodystrophy	DISOMQD2	Limited	Genetic Variation	[16]
Xeroderma pigmentosum	DISQ9H19	Limited	Genetic Variation	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Interferon-induced protein 44 (IFI44).	[17]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Interferon-induced protein 44 (IFI44).	[18]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Interferon-induced protein 44 (IFI44).	[19]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Interferon-induced protein 44 (IFI44).	[20]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Interferon-induced protein 44 (IFI44).	[21]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Interferon-induced protein 44 (IFI44).	[22]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Interferon-induced protein 44 (IFI44).	[23]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Interferon-induced protein 44 (IFI44).	[24]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Interferon-induced protein 44 (IFI44).	[25]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Interferon-induced protein 44 (IFI44).	[26]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Interferon-induced protein 44 (IFI44).	[23]
Diclofenac	DMPIHLS	Approved	Diclofenac decreases the expression of Interferon-induced protein 44 (IFI44).	[23]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Interferon-induced protein 44 (IFI44).	[27]
Prednisolone	DMQ8FR2	Approved	Prednisolone decreases the expression of Interferon-induced protein 44 (IFI44).	[23]
Methylprednisolone	DM4BDON	Approved	Methylprednisolone decreases the expression of Interferon-induced protein 44 (IFI44).	[23]
Tofacitinib	DMBS370	Approved	Tofacitinib decreases the expression of Interferon-induced protein 44 (IFI44).	[28]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Interferon-induced protein 44 (IFI44).	[29]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Interferon-induced protein 44 (IFI44).	[30]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Interferon-induced protein 44 (IFI44).	[31]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Interferon-induced protein 44 (IFI44).	[32]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Interferon-induced protein 44 (IFI44).	[33]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Interferon-induced protein 44 (IFI44).	[34]

References

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• [4] Androgen receptor coactivator p44/Mep50 in breast cancer growth and invasion.J Cell Mol Med. 2010 Dec;14(12):2780-9. doi: 10.1111/j.1582-4934.2009.00936.x.
• [5] Hepatitis C virus drives increased type I interferon-associated impairments associated with fibrosis severity in antiretroviral treatment-treated HIV-1-hepatitis C virus-coinfected individuals.AIDS. 2017 Jun 1;31(9):1223-1234. doi: 10.1097/QAD.0000000000001455.
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• [10] Long Noncoding RNA LINC01116 Contributes to Gefitinib Resistance in Non-small Cell Lung Cancer through Regulating IFI44.Mol Ther Nucleic Acids. 2020 Mar 6;19:218-227. doi: 10.1016/j.omtn.2019.10.039. Epub 2019 Nov 14.
• [11] Type I Interferon Signature in Primary Antiphospholipid Syndrome: Clinical and Laboratory Associations.Front Immunol. 2019 Mar 15;10:487. doi: 10.3389/fimmu.2019.00487. eCollection 2019.
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• [16] The intricate network between the p34 and p44 subunits is central to the activity of the transcription/DNA repair factor TFIIH.Nucleic Acids Res. 2017 Oct 13;45(18):10872-10883. doi: 10.1093/nar/gkx743.
• [17] Evaluation of a human iPSC-derived BBB model for repeated dose toxicity testing with cyclosporine A as model compound. Toxicol In Vitro. 2021 Jun;73:105112. doi: 10.1016/j.tiv.2021.105112. Epub 2021 Feb 22.
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• [19] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
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• [21] Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
• [22] 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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• [25] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [26] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
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• [34] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.