Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNNYP9A)

• DOT Name: Arpin (ARPIN)
• Synonyms: Arp2/3 inhibition protein
• Gene Name: ARPIN
• Related Disease:
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Neoplasm
  Gastric cancer
  Stomach cancer
• UniProt ID: ARPIN_HUMAN
• PDB ID: 4Z68; 7JPN
• Pfam ID: PF10574
• Sequence:
  MSRIYHDGALRNKAVQSVRLPGAWDPAAHQGGNGVLLEGELIDVSRHSILDTHGRKERYY
  VLYIRPSHIHRRKFDAKGNEIEPNFSATRKVNTGFLMSSYKVEAKGDTDRLTPEALKGLV
  NKPELLALTESLTPDHTVAFWMPESEMEVMELELGAGVRLKTRGDGPFLDSLAKLEAGTV
  TKCNFTGDGKTGASWTDNIMAQKCSKGAAAEIREQGDGAEDEEWDD
• Function: Regulates actin polymerization by inhibiting the actin-nucleating activity of the Arp2/3 complex; the function is competitive with nucleation promoting factors. Participates in an incoherent feedforward loop at the lamellipodium tip where it inhibits the ARP2/2 complex in response to Rac signaling and where Rac also stimulates actin polymerization through the WAVE complex. Involved in steering cell migration by controlling its directional persistence.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Gastric cancer	DISXGOUK	moderate	Altered Expression	[2]
Stomach cancer	DISKIJSX	moderate	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Arpin (ARPIN).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Arpin (ARPIN).	[4]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Arpin (ARPIN).	[5]
Marinol	DM70IK5	Approved	Marinol increases the expression of Arpin (ARPIN).	[6]
Permethrin	DMZ0Q1G	Approved	Permethrin decreases the expression of Arpin (ARPIN).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Arpin (ARPIN).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Arpin (ARPIN).	[9]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Arpin (ARPIN).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Arpin (ARPIN).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Arpin (ARPIN).	[10]

References

• [1] Aberrant expression of Arpin in human breast cancer and its clinical significance.J Cell Mol Med. 2016 Mar;20(3):450-8. doi: 10.1111/jcmm.12740. Epub 2015 Dec 9.
• [2] Clinicopathological and prognostic significance of aberrant Arpin expression in gastric cancer.World J Gastroenterol. 2017 Feb 28;23(8):1450-1457. doi: 10.3748/wjg.v23.i8.1450.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Arsenic alters transcriptional responses to Pseudomonas aeruginosa infection and decreases antimicrobial defense of human airway epithelial cells. Toxicol Appl Pharmacol. 2017 Sep 15;331:154-163.
• [6] 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.
• [7] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [10] 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.
• [11] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [12] 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.