Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWS90F9)

• DOT Name: Anamorsin (CIAPIN1)
• Synonyms: Cytokine-induced apoptosis inhibitor 1; Fe-S cluster assembly protein DRE2 homolog
• Gene Name: CIAPIN1
• Related Disease:
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Carcinoma of liver and intrahepatic biliary tract
  Clear cell renal carcinoma
  Colon carcinoma
  Gastric cancer
  Gastric neoplasm
  Hepatocellular carcinoma
  Liver cancer
  Neoplasm
  Non-small-cell lung cancer
  Ovarian serous adenocarcinoma
  Pancreatic cancer
  Plasma cell myeloma
  Skin disease
  Stomach cancer
  Colorectal carcinoma
  Kidney cancer
  leukaemia
  Leukemia
  Renal carcinoma
• UniProt ID: CPIN1_HUMAN
• PDB ID: 2LD4; 2YUI; 4M7R
• Pfam ID: PF20922 ; PF05093
• Sequence:
  MADFGISAGQFVAVVWDKSSPVEALKGLVDKLQALTGNEGRVSVENIKQLLQSAHKESSF
  DIILSGLVPGSTTLHSAEILAEIARILRPGGCLFLKEPVETAVDNNSKVKTASKLCSALT
  LSGLVEVKELQREPLTPEEVQSVREHLGHESDNLLFVQITGKKPNFEVGSSRQLKLSITK
  KSSPSVKPAVDPAAAKLWTLSANDMEDDSMDLIDSDELLDPEDLKKPDPASLRAASCGEG
  KKRKACKNCTCGLAEELEKEKSREQMSSQPKSACGNCYLGDAFRCASCPYLGMPAFKPGE
  KVLLSDSNLHDA
• Function: Component of the cytosolic iron-sulfur (Fe-S) protein assembly (CIA) machinery required for the maturation of extramitochondrial Fe-S proteins. Part of an electron transfer chain functioning in an early step of cytosolic Fe-S biogenesis, facilitating the de novo assembly of a [4Fe-4S] cluster on the scaffold complex NUBP1-NUBP2. Electrons are transferred to CIAPIN1 from NADPH via the FAD- and FMN-containing protein NDOR1. NDOR1-CIAPIN1 are also required for the assembly of the diferric tyrosyl radical cofactor of ribonucleotide reductase (RNR), probably by providing electrons for reduction during radical cofactor maturation in the catalytic small subunit. Has anti-apoptotic effects in the cell. Involved in negative control of cell death upon cytokine withdrawal. Promotes development of hematopoietic cells.
• Tissue Specificity: Ubiquitously expressed. Highly expressed in heart, liver and pancreas.
• Reactome Pathway: Cytosolic iron-sulfur cluster assembly (R-HSA-2564830)

Molecular Interaction Atlas (MIA) of This DOT

22 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[2]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[2]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Altered Expression	[3]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[4]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[5]
Gastric cancer	DISXGOUK	Strong	Biomarker	[6]
Gastric neoplasm	DISOKN4Y	Strong	Biomarker	[7]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[3]
Liver cancer	DISDE4BI	Strong	Altered Expression	[3]
Neoplasm	DISZKGEW	Strong	Biomarker	[8]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[9]
Ovarian serous adenocarcinoma	DISSU72Z	Strong	Biomarker	[10]
Pancreatic cancer	DISJC981	Strong	Biomarker	[11]
Plasma cell myeloma	DIS0DFZ0	Strong	Altered Expression	[12]
Skin disease	DISDW8R6	Strong	Biomarker	[13]
Stomach cancer	DISKIJSX	Strong	Biomarker	[6]
Colorectal carcinoma	DIS5PYL0	Limited	Altered Expression	[6]
Kidney cancer	DISBIPKM	Limited	Biomarker	[6]
leukaemia	DISS7D1V	Limited	Biomarker	[14]
Leukemia	DISNAKFL	Limited	Biomarker	[14]
Renal carcinoma	DISER9XT	Limited	Biomarker	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Anamorsin (CIAPIN1) decreases the response to substance of Doxorubicin.	[24]
Etoposide	DMNH3PG	Approved	Anamorsin (CIAPIN1) decreases the response to substance of Etoposide.	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Anamorsin (CIAPIN1).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Anamorsin (CIAPIN1).	[20]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Anamorsin (CIAPIN1).	[21]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Anamorsin (CIAPIN1).	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Anamorsin (CIAPIN1).	[16]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Anamorsin (CIAPIN1).	[17]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Anamorsin (CIAPIN1).	[18]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Anamorsin (CIAPIN1).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Anamorsin (CIAPIN1).	[23]

References

• [1] Down regulation of CIAPIN1 reverses multidrug resistance in human breast cancer cells by inhibiting MDR1.Molecules. 2012 Jun 20;17(6):7595-611. doi: 10.3390/molecules17067595.
• [2] Upregulation of microRNA-143 reverses drug resistance in human breast cancer cells via inhibition of cytokine-induced apoptosis inhibitor 1.Oncol Lett. 2017 Jun;13(6):4695-4700. doi: 10.3892/ol.2017.6078. Epub 2017 Apr 24.
• [3] The study on expression of CIAPIN1 interfering hepatocellular carcinoma cell proliferation and its mechanisms.Eur Rev Med Pharmacol Sci. 2017 Jul;21(13):3054-3060.
• [4] CIAPIN1 inhibits the growth and proliferation of clear cell renal cell carcinoma.Cancer Lett. 2009 Apr 8;276(1):88-94. doi: 10.1016/j.canlet.2008.10.044. Epub 2008 Dec 9.
• [5] CIAPIN1 confers multidrug resistance through up-regulation of MDR-1 and Bcl-L in LoVo/Adr cells and is independent of p53.Oncol Rep. 2011 Apr;25(4):1091-8. doi: 10.3892/or.2011.1148. Epub 2011 Jan 14.
• [6] Expression of CIAPIN1 in human colorectal cancer and its correlation with prognosis.BMC Cancer. 2010 Sep 3;10:477. doi: 10.1186/1471-2407-10-477.
• [7] CIAPIN1 inhibits gastric cancer cell proliferation and cell cycle progression by downregulating CyclinD1 and upregulating P27.Cancer Biol Ther. 2007 Oct;6(10):1539-45. doi: 10.4161/cbt.6.10.4684.
• [8] CIAPIN1 Targeted NHE1 and ERK1/2 to Suppress NSCLC Cells' Metastasis and Predicted Good Prognosis in NSCLC Patients Receiving Pulmonectomy.Oxid Med Cell Longev. 2019 Apr 9;2019:1970818. doi: 10.1155/2019/1970818. eCollection 2019.
• [9] MiRNA-195-5p Functions as a Tumor Suppressor and a Predictive of Poor Prognosis in Non-small Cell Lung Cancer by Directly Targeting CIAPIN1.Pathol Oncol Res. 2019 Jul;25(3):1181-1190. doi: 10.1007/s12253-018-0552-z. Epub 2019 Jan 12.
• [10] CIAPIN1 and ABCA13 are markers of poor survival in metastatic ovarian serous carcinoma.Mol Cancer. 2015 Feb 18;14:44. doi: 10.1186/s12943-015-0317-1.
• [11] Overexpression of CIAPIN1 inhibited pancreatic cancer cell proliferation and was associated with good prognosis in pancreatic cancer.Cancer Gene Ther. 2012 Aug;19(8):538-44. doi: 10.1038/cgt.2012.28. Epub 2012 Jun 8.
• [12] Cytokine-induced apoptosis inhibitor 1 inhibits the growth and proliferation of multiple myeloma.Mol Med Rep. 2015 Aug;12(2):2056-62. doi: 10.3892/mmr.2015.3656. Epub 2015 Apr 22.
• [13] Transduced Tat-CIAPIN1 reduces the inflammatory response on LPS- and TPA-induced damages.BMB Rep. 2019 Dec;52(12):695-699. doi: 10.5483/BMBRep.2019.52.12.245.
• [14] Knock-down of CIAPIN1 sensitizes K562 chronic myeloid leukemia cells to Imatinib by regulation of cell cycle and apoptosis-associated members via NF-B and ERK5 signaling pathway.Biochem Pharmacol. 2016 Jan 1;99:132-45. doi: 10.1016/j.bcp.2015.12.002. Epub 2015 Dec 8.
• [15] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [16] 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.
• [17] 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.
• [18] Quercetin potentiates apoptosis by inhibiting nuclear factor-kappaB signaling in H460 lung cancer cells. Biol Pharm Bull. 2013;36(6):944-51. doi: 10.1248/bpb.b12-01004.
• [19] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [20] 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.
• [21] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [22] 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.
• [23] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [24] [Reversal of multidrug resistance of gastric cancer cells by down-regulation of CIAPIN1 with CIAPIN1 siRNA]. Mol Biol (Mosk). 2008 Jan-Feb;42(1):102-9.