Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNAXGM7)

• DOT Name: Armadillo repeat-containing protein 8 (ARMC8)
• Gene Name: ARMC8
• Related Disease:
  Breast cancer
  Breast carcinoma
  Colon cancer
  Colon carcinoma
  Neoplasm
  Bladder cancer
  Lung cancer
  Lung carcinoma
  Urinary bladder cancer
  Urinary bladder neoplasm
  Bone osteosarcoma
  Lung adenocarcinoma
  Non-small-cell lung cancer
  Osteosarcoma
  Advanced cancer
• UniProt ID: ARMC8_HUMAN
• PDB ID: 7NSC
• Pfam ID: PF00514
• Sequence:
  MACLLETPIRMSVLSEVTASSRHYVDRLFDPDPQKVLQGVIDMKNAVIGNNKQKANLIVL
  GAVPRLLYLLQQETSSTELKTECAVVLGSLAMGTENNVKSLLDCHIIPALLQGLLSPDLK
  FIEACLRCLRTIFTSPVTPEELLYTDATVIPHLMALLSRSRYTQEYICQIFSHCCKGPDH
  QTILFNHGAVQNIAHLLTSLSYKVRMQALKCFSVLAFENPQVSMTLVNVLVDGELLPQIF
  VKMLQRDKPIEMQLTSAKCLTYMCRAGAIRTDDNCIVLKTLPCLVRMCSKERLLEERVEG
  AETLAYLIEPDVELQRIASITDHLIAMLADYFKYPSSVSAITDIKRLDHDLKHAHELRQA
  AFKLYASLGANDEDIRKKIIETENMMDRIVTGLSESSVKVRLAAVRCLHSLSRSVQQLRT
  SFQDHAVWKPLMKVLQNAPDEILVVASSMLCNLLLEFSPSKEPILESGAVELLCGLTQSE
  NPALRVNGIWALMNMAFQAEQKIKADILRSLSTEQLFRLLSDSDLNVLMKTLGLLRNLLS
  TRPHIDKIMSTHGKQIMQAVTLILEGEHNIEVKEQTLCILANIADGTTAKDLIMTNDDIL
  QKIKYYMGHSHVKLQLAAMFCISNLIWNEEEGSQERQDKLRDMGIVDILHKLSQSPDSNL
  CDKAKMALQQYLA
• Function: Component of the CTLH E3 ubiquitin-protein ligase complex that selectively accepts ubiquitin from UBE2H and mediates ubiquitination and subsequent proteasomal degradation of the transcription factor HBP1.
• Reactome Pathway: Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Definitive	Biomarker	[1]
Breast carcinoma	DIS2UE88	Definitive	Biomarker	[1]
Colon cancer	DISVC52G	Definitive	Biomarker	[1]
Colon carcinoma	DISJYKUO	Definitive	Biomarker	[1]
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Bladder cancer	DISUHNM0	Strong	Biomarker	[2]
Lung cancer	DISCM4YA	Strong	Altered Expression	[3]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[3]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[2]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[2]
Bone osteosarcoma	DIST1004	moderate	Biomarker	[4]
Lung adenocarcinoma	DISD51WR	moderate	Biomarker	[3]
Non-small-cell lung cancer	DIS5Y6R9	moderate	Biomarker	[1]
Osteosarcoma	DISLQ7E2	moderate	Biomarker	[4]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[5]

15 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 Armadillo repeat-containing protein 8 (ARMC8).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Armadillo repeat-containing protein 8 (ARMC8).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Armadillo repeat-containing protein 8 (ARMC8).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Armadillo repeat-containing protein 8 (ARMC8).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Armadillo repeat-containing protein 8 (ARMC8).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Armadillo repeat-containing protein 8 (ARMC8).	[11]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Armadillo repeat-containing protein 8 (ARMC8).	[12]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Armadillo repeat-containing protein 8 (ARMC8).	[13]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Armadillo repeat-containing protein 8 (ARMC8).	[14]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Armadillo repeat-containing protein 8 (ARMC8).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Armadillo repeat-containing protein 8 (ARMC8).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Armadillo repeat-containing protein 8 (ARMC8).	[17]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Armadillo repeat-containing protein 8 (ARMC8).	[18]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Armadillo repeat-containing protein 8 (ARMC8).	[19]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde decreases the expression of Armadillo repeat-containing protein 8 (ARMC8).	[20]

References

• [1] ARMc8 indicates aggressive colon cancers and promotes invasiveness and migration of colon cancer cells.Tumour Biol. 2015 Nov;36(11):9005-13. doi: 10.1007/s13277-015-3664-z. Epub 2015 Jun 18.
• [2] Silencing of Armadillo Repeat-Containing Protein 8 (ARMc8) Inhibits TGF--Induced EMT in Bladder Carcinoma UMUC3 Cells.Oncol Res. 2017 Jan 2;25(1):99-105. doi: 10.3727/096504016X14719078133609.
• [3] Comparative proteomics and global genome-wide expression data implicate role of ARMC8 in lung cancer.Asian Pac J Cancer Prev. 2015;16(9):3691-6. doi: 10.7314/apjcp.2015.16.9.3691.
• [4] Armadillo Repeat-Containing Protein 8 (ARMC8) Silencing Inhibits Proliferation and Invasion in Osteosarcoma Cells.Oncol Res. 2016;24(5):381-389. doi: 10.3727/096504016X14685034103392.
• [5] Armc8 is an evolutionarily conserved armadillo protein involved in cell-cell adhesion complexes through multiple molecular interactions.Biosci Rep. 2019 Aug 2;39(8):BSR20180604. doi: 10.1042/BSR20180604. Print 2019 Aug 30.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [7] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [8] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [9] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [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] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [15] Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
• [16] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [17] 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.
• [18] 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.
• [19] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [20] Gene expression profile and cytotoxicity of human bronchial epithelial cells exposed to crotonaldehyde. Toxicol Lett. 2010 Aug 16;197(2):113-22.