Details of Drug Off-Target (DOT)

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

• DOT Name: Cdc42 effector protein 4 (CDC42EP4)
• Synonyms: Binder of Rho GTPases 4
• Gene Name: CDC42EP4
• Related Disease:
  Asthma
  Neoplasm
  Schizophrenia
• UniProt ID: BORG4_HUMAN
• Pfam ID: PF14957 ; PF00786
• Sequence:
  MPILKQLVSSSVHSKRRSRADLTAEMISAPLGDFRHTMHVGRAGDAFGDTSFLNSKAGEP
  DGESLDEQPSSSSSKRSLLSRKFRGSKRSQSVTRGEREQRDMLGSLRDSALFVKNAMSLP
  QLNEKEAAEKGTSKLPKSLSSSPVKKANDGEGGDEEAGTEEAVPRRNGAAGPHSPDPLLD
  EQAFGDLTDLPVVPKATYGLKHAESIMSFHIDLGPSMLGDVLSIMDKEEWDPEEGEGGYH
  GDEGAAGTITQAPPYAVAAPPLARQEGKAGPDLPSLPSHALEDEGWAAAAPSPGSARSMG
  SHTTRDSSSLSSCTSGILEERSPAFRGPDRARAAVSRQPDKEFSFMDEEEEDEIRV
• Function: Probably involved in the organization of the actin cytoskeleton. May act downstream of CDC42 to induce actin filament assembly leading to cell shape changes. Induces pseudopodia formation, when overexpressed in fibroblasts.
• Tissue Specificity: Not detected in any of the adult tissues tested. May be expressed only in fetal or embryonic tissues.
• Reactome Pathway:
  RAC1 GTPase cycle (R-HSA-9013149)
  RAC2 GTPase cycle (R-HSA-9013404)
  RHOQ GTPase cycle (R-HSA-9013406)
  CDC42 GTPase cycle (R-HSA-9013148)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Asthma	DISW9QNS	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Schizophrenia	DISSRV2N	Strong	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Cdc42 effector protein 4 (CDC42EP4).	[4]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Cdc42 effector protein 4 (CDC42EP4).	[17]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Cdc42 effector protein 4 (CDC42EP4).	[17]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of Cdc42 effector protein 4 (CDC42EP4).	[20]

16 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 Cdc42 effector protein 4 (CDC42EP4).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Cdc42 effector protein 4 (CDC42EP4).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Cdc42 effector protein 4 (CDC42EP4).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Cdc42 effector protein 4 (CDC42EP4).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Cdc42 effector protein 4 (CDC42EP4).	[9]
Marinol	DM70IK5	Approved	Marinol increases the expression of Cdc42 effector protein 4 (CDC42EP4).	[10]
Selenium	DM25CGV	Approved	Selenium increases the expression of Cdc42 effector protein 4 (CDC42EP4).	[11]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Cdc42 effector protein 4 (CDC42EP4).	[8]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Cdc42 effector protein 4 (CDC42EP4).	[12]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Cdc42 effector protein 4 (CDC42EP4).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Cdc42 effector protein 4 (CDC42EP4).	[14]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Cdc42 effector protein 4 (CDC42EP4).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Cdc42 effector protein 4 (CDC42EP4).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Cdc42 effector protein 4 (CDC42EP4).	[18]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Cdc42 effector protein 4 (CDC42EP4).	[12]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Cdc42 effector protein 4 (CDC42EP4).	[19]

References

• [1] CDC42-related genes are upregulated in helper Tcells from obese asthmatic children.J Allergy Clin Immunol. 2018 Feb;141(2):539-548.e7. doi: 10.1016/j.jaci.2017.04.016. Epub 2017 May 4.
• [2] Phylogenetic analysis of multiple FISH markers in oral tongue squamous cell carcinoma suggests that a diverse distribution of copy number changes is associated with poor prognosis.Int J Cancer. 2016 Jan 1;138(1):98-109. doi: 10.1002/ijc.29691. Epub 2015 Aug 28.
• [3] Altered cortical CDC42 signaling pathways in schizophrenia: implications for dendritic spine deficits.Biol Psychiatry. 2010 Jul 1;68(1):25-32. doi: 10.1016/j.biopsych.2010.02.016. Epub 2010 Apr 10.
• [4] 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.
• [5] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Time series analysis of oxidative stress response patterns in HepG2: a toxicogenomics approach. Toxicology. 2013 Apr 5;306:24-34.
• [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] 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.
• [11] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [12] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [15] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [16] 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.
• [17] 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.
• [18] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [19] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [20] Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.