Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTX2UA7P)

• DOT Name: Ras GTPase-activating-like protein IQGAP2 (IQGAP2)
• Gene Name: IQGAP2
• Related Disease:
  Deafness
  Gastric neoplasm
  Neoplasm
  Advanced cancer
  Brain cancer
  Brain neoplasm
  Carcinoma of liver and intrahepatic biliary tract
  Colitis
  Colorectal carcinoma
  Epithelial ovarian cancer
  Fatty liver disease
  Gastric cancer
  Hepatocellular carcinoma
  Inflammatory bowel disease
  Liver cancer
  Ovarian cancer
  Ovarian neoplasm
  Schizophrenia
  Stomach cancer
  Venous thromboembolism
  Prostate cancer
  Prostate carcinoma
  Metastatic malignant neoplasm
  Rectal carcinoma
• UniProt ID: IQGA2_HUMAN
• PDB ID: 3IEZ; 4EZA; 5CJP
• Pfam ID: PF00307 ; PF00612 ; PF00616 ; PF03836
• Sequence:
  MPHEELPSLQRPRYGSIVDDERLSAEEMDERRRQNIAYEYLCHLEEAKRWMEVCLVEELP
  PTTELEEGLRNGVYLAKLAKFFAPKMVSEKKIYDVEQTRYKKSGLHFRHTDNTVQWLRAM
  ESIGLPKIFYPETTDVYDRKNIPRMIYCIHALSLYLFKLGIAPQIQDLLGKVDFTEEEIS
  NMRKELEKYGIQMPSFSKIGGILANELSVDEAALHAAVIAINEAVEKGIAEQTVVTLRNP
  NAVLTLVDDNLAPEYQKELWDAKKKKEENARLKNSCISEEERDAYEELLTQAEIQGNINK
  VNRQAAVDHINAVIPEGDPENTLLALKKPEAQLPAVYPFAAAMYQNELFNLQKQNTMNYL
  AHEELLIAVEMLSAVALLNQALESNDLVSVQNQLRSPAIGLNNLDKAYVERYANTLLSVK
  LEVLSQGQDNLSWNEIQNCIDMVNAQIQEENDRVVAVGYINEAIDEGNPLRTLETLLLPT
  ANISDVDPAHAQHYQDVLYHAKSQKLGDSESVSKVLWLDEIQQAVDDANVDKDRAKQWVT
  LVVDVNQCLEGKKSSDILSVLKSSTSNANDIIPECADKYYDALVKAKELKSERVSSDGSW
  LKLNLHKKYDYYYNTDSKESSWVTPESCLYKESWLTGKEIEDIIEEVTVGYIRENIWSAS
  EELLLRFQATSSGPILREEFEARKSFLHEQEENVVKIQAFWKGYKQRKEYMHRRQTFIDN
  TDSIVKIQSWFRMATARKSYLSRLQYFRDHNNEIVKIQSLLRANKARDDYKTLVGSENPP
  LTVIRKFVYLLDQSDLDFQEELEVARLREEVVTKIRANQQLEKDLNLMDIKIGLLVKNRI
  TLEDVISHSKKLNKKKGGEMEILNNTDNQGIKSLSKERRKTLETYQQLFYLLQTNPLYLA
  KLIFQMPQNKSTKFMDTVIFTLYNYASNQREEYLLLKLFKTALEEEIKSKVDQVQDIVTG
  NPTVIKMVVSFNRGARGQNTLRQLLAPVVKEIIDDKSLIINTNPVEVYKAWVNQLETQTG
  EASKLPYDVTTEQALTYPEVKNKLEASIENLRRVTDKVLNSIISSLDLLPYGLRYIAKVL
  KNSIHEKFPDATEDELLKIVGNLLYYRYMNPAIVAPDGFDIIDMTAGGQINSDQRRNLGS
  VAKVLQHAASNKLFEGENEHLSSMNNYLSETYQEFRKYFKEACNVPEPEEKFNMDKYTDL
  VTVSKPVIYISIEEIISTHSLLLEHQDAIAPEKNDLLSELLGSLGEVPTVESFLGEGAVD
  PNDPNKANTLSQLSKTEISLVLTSKYDIEDGEAIDSRSLMIKTKKLIIDVIRNQPGNTLT
  EILETPATAQQEVDHATDMVSRAMIDSRTPEEMKHSQSMIEDAQLPLEQKKRKIQRNLRT
  LEQTGHVSSENKYQDILNEIAKDIRNQRIYRKLRKAELAKLQQTLNALNKKAAFYEEQIN
  YYDTYIKTCLDNLKRKNTRRSIKLDGKGEPKGAKRAKPVKYTAAKLHEKGVLLDIDDLQT
  NQFKNVTFDIIATEDVGIFDVRSKFLGVEMEKVQLNIQDLLQMQYEGVAVMKMFDKVKVN
  VNLLIYLLNKKFYGK
• Function: Binds to activated CDC42 and RAC1 but does not seem to stimulate their GTPase activity. Associates with calmodulin.
• Tissue Specificity: Isoform 2 expression is enhanced in testis.
• KEGG Pathway: Regulation of actin cytoskeleton (hsa04810)
• Reactome Pathway:
  Neutrophil degranulation (R-HSA-6798695)
  CDC42 GTPase cycle (R-HSA-9013148)
  RAC1 GTPase cycle (R-HSA-9013149)
  RHOG GTPase cycle (R-HSA-9013408)
  RHO GTPases activate IQGAPs (R-HSA-5626467)

Molecular Interaction Atlas (MIA) of This DOT

24 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Deafness	DISKCLH4	Definitive	Genetic Variation	[1]
Gastric neoplasm	DISOKN4Y	Definitive	Posttranslational Modification	[2]
Neoplasm	DISZKGEW	Definitive	Biomarker	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Brain cancer	DISBKFB7	Strong	Biomarker	[5]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[5]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Biomarker	[6]
Colitis	DISAF7DD	Strong	Biomarker	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[7]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[8]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[9]
Gastric cancer	DISXGOUK	Strong	Biomarker	[10]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[11]
Inflammatory bowel disease	DISGN23E	Strong	Genetic Variation	[4]
Liver cancer	DISDE4BI	Strong	Biomarker	[12]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[8]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[8]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[13]
Stomach cancer	DISKIJSX	Strong	Biomarker	[10]
Venous thromboembolism	DISUR7CR	Strong	Genetic Variation	[14]
Prostate cancer	DISF190Y	moderate	Altered Expression	[3]
Prostate carcinoma	DISMJPLE	moderate	Altered Expression	[3]
Metastatic malignant neoplasm	DIS86UK6	Disputed	Altered Expression	[3]
Rectal carcinoma	DIS8FRR7	Limited	Altered Expression	[15]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Chlorothiazide	DMLHESP	Approved	Ras GTPase-activating-like protein IQGAP2 (IQGAP2) increases the Metabolic disorder ADR of Chlorothiazide.	[39]

2 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 Ras GTPase-activating-like protein IQGAP2 (IQGAP2).	[16]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Ras GTPase-activating-like protein IQGAP2 (IQGAP2).	[36]

22 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 Ras GTPase-activating-like protein IQGAP2 (IQGAP2).	[17]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Ras GTPase-activating-like protein IQGAP2 (IQGAP2).	[18]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Ras GTPase-activating-like protein IQGAP2 (IQGAP2).	[19]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Ras GTPase-activating-like protein IQGAP2 (IQGAP2).	[20]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ras GTPase-activating-like protein IQGAP2 (IQGAP2).	[21]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Ras GTPase-activating-like protein IQGAP2 (IQGAP2).	[22]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Ras GTPase-activating-like protein IQGAP2 (IQGAP2).	[23]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Ras GTPase-activating-like protein IQGAP2 (IQGAP2).	[24]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Ras GTPase-activating-like protein IQGAP2 (IQGAP2).	[25]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Ras GTPase-activating-like protein IQGAP2 (IQGAP2).	[26]
Enzalutamide	DMGL19D	Approved	Enzalutamide decreases the expression of Ras GTPase-activating-like protein IQGAP2 (IQGAP2).	[27]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Ras GTPase-activating-like protein IQGAP2 (IQGAP2).	[28]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Ras GTPase-activating-like protein IQGAP2 (IQGAP2).	[27]
Isoflavone	DM7U58J	Phase 4	Isoflavone decreases the expression of Ras GTPase-activating-like protein IQGAP2 (IQGAP2).	[29]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Ras GTPase-activating-like protein IQGAP2 (IQGAP2).	[23]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Ras GTPase-activating-like protein IQGAP2 (IQGAP2).	[30]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Ras GTPase-activating-like protein IQGAP2 (IQGAP2).	[31]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Ras GTPase-activating-like protein IQGAP2 (IQGAP2).	[33]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Ras GTPase-activating-like protein IQGAP2 (IQGAP2).	[34]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Ras GTPase-activating-like protein IQGAP2 (IQGAP2).	[35]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Ras GTPase-activating-like protein IQGAP2 (IQGAP2).	[37]
ELLAGIC ACID	DMX8BS5	Investigative	ELLAGIC ACID increases the expression of Ras GTPase-activating-like protein IQGAP2 (IQGAP2).	[38]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Ras GTPase-activating-like protein IQGAP2 (IQGAP2).	[32]

References

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