Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOZ6PIM)

• DOT Name: Neuronal-specific septin-3 (SEPTIN3)
• Gene Name: SEPTIN3
• Related Disease:
  Cystic fibrosis
  Leukopenia
  Peripheral neuropathy
  Spinocerebellar ataxia type 2
  Vibrio cholerae infection
• UniProt ID: SEPT3_HUMAN
• PDB ID: 3SOP; 4Z51; 4Z54; 6UQQ
• Pfam ID: PF00735
• Sequence:
  MSKGLPETRTDAAMSELVPEPRPKPAVPMKPMSINSNLLGYIGIDTIIEQMRKKTMKTGF
  DFNIMVVGQSGLGKSTLVNTLFKSQVSRKASSWNREEKIPKTVEIKAIGHVIEEGGVKMK
  LTVIDTPGFGDQINNENCWEPIEKYINEQYEKFLKEEVNIARKKRIPDTRVHCCLYFISP
  TGHSLRPLDLEFMKHLSKVVNIIPVIAKADTMTLEEKSEFKQRVRKELEVNGIEFYPQKE
  FDEDLEDKTENDKIRQESMPFAVVGSDKEYQVNGKRVLGRKTPWGIIEVENLNHCEFALL
  RDFVIRTHLQDLKEVTHNIHYETYRAKRLNDNGGLPPGEGLLGTVLPPVPATPCPTAE
• Function: Filament-forming cytoskeletal GTPase. May play a role in cytokinesis (Potential).
• Tissue Specificity: Brain-specific.
• KEGG Pathway:
  Bacterial invasion of epithelial cells (hsa05100)
  Shigellosis (hsa05131)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cystic fibrosis	DIS2OK1Q	Strong	Genetic Variation	[1]
Leukopenia	DISJMBMM	Strong	Genetic Variation	[2]
Peripheral neuropathy	DIS7KN5G	Strong	Genetic Variation	[2]
Spinocerebellar ataxia type 2	DISF7WDI	Strong	Genetic Variation	[3]
Vibrio cholerae infection	DISW7E3U	Strong	Genetic Variation	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Neuronal-specific septin-3 (SEPTIN3).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Neuronal-specific septin-3 (SEPTIN3).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Neuronal-specific septin-3 (SEPTIN3).	[7]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Neuronal-specific septin-3 (SEPTIN3).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Neuronal-specific septin-3 (SEPTIN3).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Neuronal-specific septin-3 (SEPTIN3).	[10]
Scriptaid	DM9JZ21	Preclinical	Scriptaid affects the expression of Neuronal-specific septin-3 (SEPTIN3).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Neuronal-specific septin-3 (SEPTIN3).	[12]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Neuronal-specific septin-3 (SEPTIN3).	[13]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Neuronal-specific septin-3 (SEPTIN3).	[14]

References

• [1] The social network of cystic fibrosis centre care and shared Pseudomonas aeruginosa strain infection: a cross-sectional analysis.Lancet Respir Med. 2015 Aug;3(8):640-50. doi: 10.1016/S2213-2600(15)00228-3. Epub 2015 Jul 22.
• [2] Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial.Lancet Oncol. 2020 Jan;21(1):44-59. doi: 10.1016/S1470-2045(19)30689-8. Epub 2019 Nov 27.
• [3] Progression of early features of spinocerebellar ataxia type 2 in individuals at risk: a longitudinal study.Lancet Neurol. 2014 May;13(5):482-9. doi: 10.1016/S1474-4422(14)70027-4. Epub 2014 Mar 20.
• [4] Classical Vibrio cholerae biotype displaces EL tor in Bangladesh.Lancet. 1983 Apr 9;1(8328):805-7. doi: 10.1016/s0140-6736(83)91860-3.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] 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.
• [7] 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.
• [8] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [9] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [10] 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.
• [11] Histone deacetylase inhibitor scriptaid induces cell cycle arrest and epigenetic change in colon cancer cells. Int J Oncol. 2008 Oct;33(4):767-76.
• [12] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [13] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [14] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.