Details of Drug Off-Target (DOT)

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

• DOT Name: Rho GDP-dissociation inhibitor 1 (ARHGDIA)
• Synonyms: Rho GDI 1; Rho-GDI alpha
• Gene Name: ARHGDIA
• Related Disease:
  Tubular aggregate myopathy
  Breast cancer
  Breast carcinoma
  Carcinoma
  Colorectal carcinoma
  Colorectal neoplasm
  Glioma
  Hepatocellular carcinoma
  HIV infectious disease
  Keloid
  Lung adenocarcinoma
  Neoplasm
  Nephrotic syndrome
  Nephrotic syndrome, type 2
  Nephrotic syndrome, type 8
  Severe congenital neutropenia
  Advanced cancer
  Breast neoplasm
  Squamous cell carcinoma
  Familial idiopathic steroid-resistant nephrotic syndrome
  Crohn disease
  High blood pressure
  Ulcerative colitis
  Invasive ductal breast carcinoma
  Prostate cancer
  Prostate carcinoma
• UniProt ID: GDIR1_HUMAN
• PDB ID: 1CC0; 1FSO; 1FST; 1FT0; 1FT3; 1HH4; 1KMT; 1QVY; 1RHO; 2BXW; 2JHS; 2JHT; 2JHU; 2JHV; 2JHW; 2JHX; 2JHY; 2JHZ; 2JI0; 2N80
• Pfam ID: PF02115
• Sequence:
  MAEQEPTAEQLAQIAAENEEDEHSVNYKPPAQKSIQEIQELDKDDESLRKYKEALLGRVA
  VSADPNVPNVVVTGLTLVCSSAPGPLELDLTGDLESFKKQSFVLKEGVEYRIKISFRVNR
  EIVSGMKYIQHTYRKGVKIDKTDYMVGSYGPRAEEYEFLTPVEEAPKGMLARGSYSIKSR
  FTDDDKTDHLSWEWNLTIKKDWKD
• Function: Controls Rho proteins homeostasis. Regulates the GDP/GTP exchange reaction of the Rho proteins by inhibiting the dissociation of GDP from them, and the subsequent binding of GTP to them. Retains Rho proteins such as CDC42, RAC1 and RHOA in an inactive cytosolic pool, regulating their stability and protecting them from degradation. Actively involved in the recycling and distribution of activated Rho GTPases in the cell, mediates extraction from membranes of both inactive and activated molecules due its exceptionally high affinity for prenylated forms. Through the modulation of Rho proteins, may play a role in cell motility regulation. In glioma cells, inhibits cell migration and invasion by mediating the signals of SEMA5A and PLXNB3 that lead to inactivation of RAC1.
• KEGG Pathway:
  Neurotrophin sig.ling pathway (hsa04722)
  Vasopressin-regulated water reabsorption (hsa04962)
• Reactome Pathway:
  Axonal growth stimulation (R-HSA-209563)
  RHOA GTPase cycle (R-HSA-8980692)
  RHOC GTPase cycle (R-HSA-9013106)
  CDC42 GTPase cycle (R-HSA-9013148)
  RAC1 GTPase cycle (R-HSA-9013149)
  RAC2 GTPase cycle (R-HSA-9013404)
  RHOH GTPase cycle (R-HSA-9013407)
  RHOG GTPase cycle (R-HSA-9013408)
  Axonal growth inhibition (RHOA activation) (R-HSA-193634)

Molecular Interaction Atlas (MIA) of This DOT

26 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Tubular aggregate myopathy	DISC11WH	Definitive	Altered Expression	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Carcinoma	DISH9F1N	Strong	Altered Expression	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[4]
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[5]
Glioma	DIS5RPEH	Strong	Altered Expression	[6]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[7]
HIV infectious disease	DISO97HC	Strong	Biomarker	[8]
Keloid	DISV09JY	Strong	Biomarker	[9]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[10]
Neoplasm	DISZKGEW	Strong	Altered Expression	[11]
Nephrotic syndrome	DISSPSC2	Strong	Biomarker	[12]
Nephrotic syndrome, type 2	DISIRFO1	Strong	GermlineCausalMutation	[13]
Nephrotic syndrome, type 8	DISSPED4	Strong	Autosomal recessive	[14]
Severe congenital neutropenia	DISES99N	Strong	Posttranslational Modification	[15]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[16]
Breast neoplasm	DISNGJLM	moderate	Altered Expression	[17]
Squamous cell carcinoma	DISQVIFL	moderate	Altered Expression	[18]
Familial idiopathic steroid-resistant nephrotic syndrome	DISQ53RS	Supportive	Autosomal dominant	[13]
Crohn disease	DIS2C5Q8	Disputed	Altered Expression	[19]
High blood pressure	DISY2OHH	Disputed	Biomarker	[20]
Ulcerative colitis	DIS8K27O	Disputed	Altered Expression	[19]
Invasive ductal breast carcinoma	DIS43J58	Limited	Altered Expression	[21]
Prostate cancer	DISF190Y	Limited	Biomarker	[22]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[22]

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Rho GDP-dissociation inhibitor 1 (ARHGDIA) affects the response to substance of Methotrexate.	[50]
Paclitaxel	DMLB81S	Approved	Rho GDP-dissociation inhibitor 1 (ARHGDIA) affects the response to substance of Paclitaxel.	[51]
Busulfan	DMXYJ9C	Approved	Rho GDP-dissociation inhibitor 1 (ARHGDIA) affects the response to substance of Busulfan.	[51]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Rho GDP-dissociation inhibitor 1 (ARHGDIA).	[23]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Rho GDP-dissociation inhibitor 1 (ARHGDIA).	[24]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Rho GDP-dissociation inhibitor 1 (ARHGDIA).	[25]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Rho GDP-dissociation inhibitor 1 (ARHGDIA).	[26]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Rho GDP-dissociation inhibitor 1 (ARHGDIA).	[27]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Rho GDP-dissociation inhibitor 1 (ARHGDIA).	[28]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Rho GDP-dissociation inhibitor 1 (ARHGDIA).	[29]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Rho GDP-dissociation inhibitor 1 (ARHGDIA).	[30]
Marinol	DM70IK5	Approved	Marinol increases the expression of Rho GDP-dissociation inhibitor 1 (ARHGDIA).	[31]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Rho GDP-dissociation inhibitor 1 (ARHGDIA).	[32]
Selenium	DM25CGV	Approved	Selenium increases the expression of Rho GDP-dissociation inhibitor 1 (ARHGDIA).	[33]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Rho GDP-dissociation inhibitor 1 (ARHGDIA).	[34]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Rho GDP-dissociation inhibitor 1 (ARHGDIA).	[35]
Hydroquinone	DM6AVR4	Approved	Hydroquinone affects the expression of Rho GDP-dissociation inhibitor 1 (ARHGDIA).	[36]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Rho GDP-dissociation inhibitor 1 (ARHGDIA).	[28]
Estrone	DM5T6US	Approved	Estrone decreases the expression of Rho GDP-dissociation inhibitor 1 (ARHGDIA).	[28]
Ampicillin	DMHWE7P	Approved	Ampicillin increases the expression of Rho GDP-dissociation inhibitor 1 (ARHGDIA).	[37]
Etretinate	DM2CZFA	Approved	Etretinate increases the expression of Rho GDP-dissociation inhibitor 1 (ARHGDIA).	[38]
Estriol	DMOEM2I	Approved	Estriol decreases the expression of Rho GDP-dissociation inhibitor 1 (ARHGDIA).	[28]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Rho GDP-dissociation inhibitor 1 (ARHGDIA).	[39]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Rho GDP-dissociation inhibitor 1 (ARHGDIA).	[28]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Rho GDP-dissociation inhibitor 1 (ARHGDIA).	[33]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Rho GDP-dissociation inhibitor 1 (ARHGDIA).	[42]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Rho GDP-dissociation inhibitor 1 (ARHGDIA).	[44]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Rho GDP-dissociation inhibitor 1 (ARHGDIA).	[30]
Manganese	DMKT129	Investigative	Manganese decreases the expression of Rho GDP-dissociation inhibitor 1 (ARHGDIA).	[45]
Arachidonic acid	DMUOQZD	Investigative	Arachidonic acid increases the expression of Rho GDP-dissociation inhibitor 1 (ARHGDIA).	[46]
Daidzein	DMRFTJX	Investigative	Daidzein decreases the expression of Rho GDP-dissociation inhibitor 1 (ARHGDIA).	[47]
Paraoxon	DMN4ZKC	Investigative	Paraoxon increases the expression of Rho GDP-dissociation inhibitor 1 (ARHGDIA).	[48]
Pyrrolidine dithiocarbamate	DM5ZAS6	Investigative	Pyrrolidine dithiocarbamate decreases the expression of Rho GDP-dissociation inhibitor 1 (ARHGDIA).	[49]

3 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 Rho GDP-dissociation inhibitor 1 (ARHGDIA).	[40]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Rho GDP-dissociation inhibitor 1 (ARHGDIA).	[41]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Rho GDP-dissociation inhibitor 1 (ARHGDIA).	[43]

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