Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9PD6CS)

• DOT Name: Rho GDP-dissociation inhibitor 2 (ARHGDIB)
• Synonyms: Rho GDI 2; Ly-GDI; Rho-GDI beta
• Gene Name: ARHGDIB
• Related Disease:
  Gastric neoplasm
  Melanoma
  Adenocarcinoma
  Adenoma
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Carcinoma
  Classic Hodgkin lymphoma
  Clear cell renal carcinoma
  Colorectal carcinoma
  Gastric cancer
  Hepatocellular carcinoma
  HIV infectious disease
  Lung neoplasm
  Neoplasm
  Pancreatic cancer
  Pancreatic tumour
  Renal cell carcinoma
  Severe congenital neutropenia
  Stomach cancer
  Systemic lupus erythematosus
  Lung cancer
  Lung carcinoma
  Acute coronary syndrome
• UniProt ID: GDIR2_HUMAN
• PDB ID: 1DS6; 5H1D
• Pfam ID: PF02115
• Sequence:
  MTEKAPEPHVEEDDDDELDSKLNYKPPPQKSLKELQEMDKDDESLIKYKKTLLGDGPVVT
  DPKAPNVVVTRLTLVCESAPGPITMDLTGDLEALKKETIVLKEGSEYRVKIHFKVNRDIV
  SGLKYVQHTYRTGVKVDKATFMVGSYGPRPEEYEFLTPVEEAPKGMLARGTYHNKSFFTD
  DDKQDHLSWEWNLSIKKEWTE
• Function: 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. Regulates reorganization of the actin cytoskeleton mediated by Rho family members.
• Tissue Specificity: Detected in bone marrow, thymus and spleen.
• KEGG Pathway:
  Neurotrophin sig.ling pathway (hsa04722)
  Vasopressin-regulated water reabsorption (hsa04962)
• Reactome Pathway:
  CDC42 GTPase cycle (R-HSA-9013148)
  RAC1 GTPase cycle (R-HSA-9013149)
  RHOH GTPase cycle (R-HSA-9013407)
  RHOG GTPase cycle (R-HSA-9013408)
  RAC3 GTPase cycle (R-HSA-9013423)
  RHOA GTPase cycle (R-HSA-8980692)

Molecular Interaction Atlas (MIA) of This DOT

25 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gastric neoplasm	DISOKN4Y	Definitive	Biomarker	[1]
Melanoma	DIS1RRCY	Definitive	Altered Expression	[2]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[3]
Adenoma	DIS78ZEV	Strong	Altered Expression	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[5]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[5]
Carcinoma	DISH9F1N	Strong	Altered Expression	[3]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Altered Expression	[6]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[7]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[8]
Gastric cancer	DISXGOUK	Strong	Biomarker	[9]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[10]
HIV infectious disease	DISO97HC	Strong	Biomarker	[11]
Lung neoplasm	DISVARNB	Strong	Biomarker	[12]
Neoplasm	DISZKGEW	Strong	Biomarker	[10]
Pancreatic cancer	DISJC981	Strong	Biomarker	[4]
Pancreatic tumour	DIS3U0LK	Strong	Biomarker	[4]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[7]
Severe congenital neutropenia	DISES99N	Strong	Posttranslational Modification	[13]
Stomach cancer	DISKIJSX	Strong	Biomarker	[9]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[14]
Lung cancer	DISCM4YA	moderate	Biomarker	[15]
Lung carcinoma	DISTR26C	moderate	Biomarker	[15]
Acute coronary syndrome	DIS7DYEW	Limited	Biomarker	[16]

31 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 Rho GDP-dissociation inhibitor 2 (ARHGDIB).	[17]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Rho GDP-dissociation inhibitor 2 (ARHGDIB).	[18]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Rho GDP-dissociation inhibitor 2 (ARHGDIB).	[19]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Rho GDP-dissociation inhibitor 2 (ARHGDIB).	[20]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Rho GDP-dissociation inhibitor 2 (ARHGDIB).	[21]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Rho GDP-dissociation inhibitor 2 (ARHGDIB).	[22]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Rho GDP-dissociation inhibitor 2 (ARHGDIB).	[24]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Rho GDP-dissociation inhibitor 2 (ARHGDIB).	[25]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Rho GDP-dissociation inhibitor 2 (ARHGDIB).	[26]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Rho GDP-dissociation inhibitor 2 (ARHGDIB).	[27]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Rho GDP-dissociation inhibitor 2 (ARHGDIB).	[28]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Rho GDP-dissociation inhibitor 2 (ARHGDIB).	[29]
Phenobarbital	DMXZOCG	Approved	Phenobarbital decreases the expression of Rho GDP-dissociation inhibitor 2 (ARHGDIB).	[30]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil affects the expression of Rho GDP-dissociation inhibitor 2 (ARHGDIB).	[31]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Rho GDP-dissociation inhibitor 2 (ARHGDIB).	[32]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Rho GDP-dissociation inhibitor 2 (ARHGDIB).	[33]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Rho GDP-dissociation inhibitor 2 (ARHGDIB).	[34]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of Rho GDP-dissociation inhibitor 2 (ARHGDIB).	[35]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Rho GDP-dissociation inhibitor 2 (ARHGDIB).	[36]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide increases the expression of Rho GDP-dissociation inhibitor 2 (ARHGDIB).	[35]
Diphenylpyraline	DMW4X37	Approved	Diphenylpyraline decreases the expression of Rho GDP-dissociation inhibitor 2 (ARHGDIB).	[37]
Dactinomycin	DM2YGNW	Approved	Dactinomycin increases the expression of Rho GDP-dissociation inhibitor 2 (ARHGDIB).	[35]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Rho GDP-dissociation inhibitor 2 (ARHGDIB).	[38]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of Rho GDP-dissociation inhibitor 2 (ARHGDIB).	[39]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Rho GDP-dissociation inhibitor 2 (ARHGDIB).	[41]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Rho GDP-dissociation inhibitor 2 (ARHGDIB).	[42]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Rho GDP-dissociation inhibitor 2 (ARHGDIB).	[43]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Rho GDP-dissociation inhibitor 2 (ARHGDIB).	[44]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Rho GDP-dissociation inhibitor 2 (ARHGDIB).	[45]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Rho GDP-dissociation inhibitor 2 (ARHGDIB).	[46]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Rho GDP-dissociation inhibitor 2 (ARHGDIB).	[47]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Rho GDP-dissociation inhibitor 2 (ARHGDIB).	[23]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Rho GDP-dissociation inhibitor 2 (ARHGDIB).	[40]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Myricetin	DMTV4L0	Investigative	Myricetin increases the cleavage of Rho GDP-dissociation inhibitor 2 (ARHGDIB).	[48]
PGJ2	DMR2LTC	Investigative	PGJ2 increases the cleavage of Rho GDP-dissociation inhibitor 2 (ARHGDIB).	[49]
PGD2	DMYDW6J	Investigative	PGD2 increases the cleavage of Rho GDP-dissociation inhibitor 2 (ARHGDIB).	[49]

References

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