Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4RZV2M)

• DOT Name: Ras GTPase-activating-like protein IQGAP3 (IQGAP3)
• Gene Name: IQGAP3
• Related Disease:
  Autism spectrum disorder
  Neoplasm
  Advanced cancer
  B-cell neoplasm
  Bladder cancer
  Breast cancer
  Breast carcinoma
  Hepatocellular carcinoma
  Urinary bladder cancer
  Urinary bladder neoplasm
  Lung cancer
  Lung carcinoma
  Colorectal carcinoma
  Gastric cancer
  Stomach cancer
• UniProt ID: IQGA3_HUMAN
• PDB ID: 3ISU
• Pfam ID: PF00307 ; PF00612 ; PF00616 ; PF03836
• Sequence:
  MERRAAGPGWAAYERLTAEEMDEQRRQNVAYQYLCRLEEAKRWMEACLKEELPSPVELEE
  SLRNGVLLAKLGHCFAPSVVPLKKIYDVEQLRYQATGLHFRHTDNINFWLSAIAHIGLPS
  TFFPETTDIYDKKNMPRVVYCIHALSLFLFRLGLAPQIHDLYGKVKFTAEELSNMASELA
  KYGLQLPAFSKIGGILANELSVDEAAVHAAVLAINEAVERGVVEDTLAALQNPSALLENL
  REPLAAVYQEMLAQAKMEKAANARNHDDRESQDIYDHYLTQAEIQGNINHVNVHGALEVV
  DDALERQSPEALLKALQDPALALRGVRRDFADWYLEQLNSDREQKAQELGLVELLEKEEV
  QAGVAAANTKGDQEQAMLHAVQRINKAIRRRVAADTVKELMCPEAQLPPVYPVASSMYQL
  ELAVLQQQQGELGQEELFVAVEMLSAVVLINRALEARDASGFWSSLVNPATGLAEVEGEN
  AQRYFDALLKLRQERGMGEDFLSWNDLQATVSQVNAQTQEETDRVLAVSLINEALDKGSP
  EKTLSALLLPAAGLDDVSLPVAPRYHLLLVAAKRQKAQVTGDPGAVLWLEEIRQGVVRAN
  QDTNTAQRMALGVAAINQAIKEGKAAQTERVLRNPAVALRGVVPDCANGYQRALESAMAK
  KQRPADTAFWVQHDMKDGTAYYFHLQTFQGIWEQPPGCPLNTSHLTREEIQSAVTKVTAA
  YDRQQLWKANVGFVIQLQARLRGFLVRQKFAEHSHFLRTWLPAVIKIQAHWRGYRQRKIY
  LEWLQYFKANLDAIIKIQAWARMWAARRQYLRRLHYFQKNVNSIVKIQAFFRARKAQDDY
  RILVHAPHPPLSVVRRFAHLLNQSQQDFLAEAELLKLQEEVVRKIRSNQQLEQDLNIMDI
  KIGLLVKNRITLQEVVSHCKKLTKRNKEQLSDMMVLDKQKGLKSLSKEKRQKLEAYQHLF
  YLLQTQPIYLAKLIFQMPQNKTTKFMEAVIFSLYNYASSRREAYLLLQLFKTALQEEIKS
  KVEQPQDVVTGNPTVVRLVVRFYRNGRGQSALQEILGKVIQDVLEDKVLSVHTDPVHLYK
  NWINQTEAQTGQRSHLPYDVTPEQALSHPEVQRRLDIALRNLLAMTDKFLLAITSSVDQI
  PYGMRYVAKVLKATLAEKFPDATDSEVYKVVGNLLYYRFLNPAVVAPDAFDIVAMAAGGA
  LAAPQRHALGAVAQLLQHAAAGKAFSGQSQHLRVLNDYLEETHLKFRKFIHRACQVPEPE
  ERFAVDEYSDMVAVAKPMVYITVGELVNTHRLLLEHQDCIAPDHQDPLHELLEDLGELPT
  IPDLIGESIAADGHTDLSKLEVSLTLTNKFEGLEADADDSNTRSLLLSTKQLLADIIQFH
  PGDTLKEILSLSASREQEAAHKQLMSRRQACTAQTPEPLRRHRSLTAHSLLPLAEKQRRV
  LRNLRRLEALGLVSARNGYQGLVDELAKDIRNQHRHRHRRKAELVKLQATLQGLSTKTTF
  YEEQGDYYSQYIRACLDHLAPDSKSSGKGKKQPSLHYTAAQLLEKGVLVEIEDLPASHFR
  NVIFDITPGDEAGKFEVNAKFLGVDMERFQLHYQDLLQLQYEGVAVMKLFNKAKVNVNLL
  IFLLNKKFLRK
• KEGG Pathway: Regulation of actin cytoskeleton (hsa04810)
• Reactome Pathway:
  RHOA GTPase cycle (R-HSA-8980692)
  RHOB GTPase cycle (R-HSA-9013026)
  RHOC GTPase cycle (R-HSA-9013106)
  CDC42 GTPase cycle (R-HSA-9013148)
  RAC1 GTPase cycle (R-HSA-9013149)
  RHOQ GTPase cycle (R-HSA-9013406)
  RHOJ GTPase cycle (R-HSA-9013409)
  RHO GTPases activate IQGAPs (R-HSA-5626467)

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autism spectrum disorder	DISXK8NV	Definitive	Biomarker	[1]
Neoplasm	DISZKGEW	Definitive	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
B-cell neoplasm	DISVY326	Strong	Altered Expression	[4]
Bladder cancer	DISUHNM0	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[4]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[4]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[6]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[5]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[5]
Lung cancer	DISCM4YA	moderate	Biomarker	[7]
Lung carcinoma	DISTR26C	moderate	Biomarker	[7]
Colorectal carcinoma	DIS5PYL0	Limited	Altered Expression	[8]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[9]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[9]

18 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 Ras GTPase-activating-like protein IQGAP3 (IQGAP3).	[10]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Ras GTPase-activating-like protein IQGAP3 (IQGAP3).	[11]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ras GTPase-activating-like protein IQGAP3 (IQGAP3).	[12]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Ras GTPase-activating-like protein IQGAP3 (IQGAP3).	[13]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Ras GTPase-activating-like protein IQGAP3 (IQGAP3).	[14]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ras GTPase-activating-like protein IQGAP3 (IQGAP3).	[15]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Ras GTPase-activating-like protein IQGAP3 (IQGAP3).	[16]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Ras GTPase-activating-like protein IQGAP3 (IQGAP3).	[16]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Ras GTPase-activating-like protein IQGAP3 (IQGAP3).	[17]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Ras GTPase-activating-like protein IQGAP3 (IQGAP3).	[18]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Ras GTPase-activating-like protein IQGAP3 (IQGAP3).	[19]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Ras GTPase-activating-like protein IQGAP3 (IQGAP3).	[20]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Ras GTPase-activating-like protein IQGAP3 (IQGAP3).	[21]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of Ras GTPase-activating-like protein IQGAP3 (IQGAP3).	[22]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Ras GTPase-activating-like protein IQGAP3 (IQGAP3).	[24]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Ras GTPase-activating-like protein IQGAP3 (IQGAP3).	[25]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Ras GTPase-activating-like protein IQGAP3 (IQGAP3).	[27]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Ras GTPase-activating-like protein IQGAP3 (IQGAP3).	[14]

2 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 increases the methylation of Ras GTPase-activating-like protein IQGAP3 (IQGAP3).	[23]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Ras GTPase-activating-like protein IQGAP3 (IQGAP3).	[26]

References

• [1] Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases. Nat Genet. 2017 Apr;49(4):515-526. doi: 10.1038/ng.3792. Epub 2017 Feb 13.
• [2] Urinary cell-free nucleic acid IQGAP3: a new non-invasive diagnostic marker for bladder cancer.Oncotarget. 2018 Feb 7;9(18):14354-14365. doi: 10.18632/oncotarget.24436. eCollection 2018 Mar 6.
• [3] Role of IQGAP3 in metastasis and epithelial-mesenchymal transition in human hepatocellular carcinoma.J Transl Med. 2017 Aug 15;15(1):176. doi: 10.1186/s12967-017-1275-8.
• [4] IQ Motif Containing GTPase-Activating Protein 3 (IQGAP3) Inhibits Kaempferol-Induced Apoptosis in Breast Cancer Cells by Extracellular Signal-Regulated Kinases 1/2 (ERK1/2) Signaling Activation.Med Sci Monit. 2019 Oct 12;25:7666-7674. doi: 10.12659/MSM.915642.
• [5] Diagnostic value of combined IQGAP3/BMP4 and IQGAP3/FAM107A expression ratios in urinary cell-free DNA for discriminating bladder cancer from hematuria.Urol Oncol. 2019 Jan;37(1):86-96. doi: 10.1016/j.urolonc.2018.10.023. Epub 2018 Nov 13.
• [6] E2F1 transactivates IQGAP3 and promotes proliferation of hepatocellular carcinoma cells through IQGAP3-mediated PKC-alpha activation.Am J Cancer Res. 2019 Feb 1;9(2):285-299. eCollection 2019.
• [7] IQGAP3 promotes EGFR-ERK signaling and the growth and metastasis of lung cancer cells.PLoS One. 2014 May 21;9(5):e97578. doi: 10.1371/journal.pone.0097578. eCollection 2014.
• [8] High expression of IQGAP3 indicates poor prognosis in colorectal cancer patients.Int J Biol Markers. 2019 Dec;34(4):348-355. doi: 10.1177/1724600819876951. Epub 2019 Sep 23.
• [9] Overexpression of the Transmembrane Protein IQGAP3 Is Associated with Poor Survival of Patients with Gastric Cancer.Pathobiology. 2018;85(3):192-200. doi: 10.1159/000481890. Epub 2017 Nov 1.
• [10] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [11] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [12] RNA sequence analysis of inducible pluripotent stem cell-derived cardiomyocytes reveals altered expression of DNA damage and cell cycle genes in response to doxorubicin. Toxicol Appl Pharmacol. 2018 Oct 1;356:44-53.
• [13] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [14] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [15] 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.
• [16] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [17] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [18] Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
• [19] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [20] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [21] Lucanthone is a novel inhibitor of autophagy that induces cathepsin D-mediated apoptosis. J Biol Chem. 2011 Feb 25;286(8):6602-13.
• [22] Phenethyl isothiocyanate alters the gene expression and the levels of protein associated with cell cycle regulation in human glioblastoma GBM 8401 cells. Environ Toxicol. 2017 Jan;32(1):176-187.
• [23] 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.
• [24] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [25] 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.
• [26] 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.
• [27] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.