Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5QBC5M)

• DOT Name: Cell division control protein 42 homolog (CDC42)
• Synonyms: EC 3.6.5.2; G25K GTP-binding protein
• Gene Name: CDC42
• Related Disease:
  Macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome
  Matthew-Wood syndrome
  Adrenal gland cancer
  Adrenal gland neoplasm
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Carcinoma
  Cervical cancer
  Colon cancer
  Colon carcinoma
  Colorectal neoplasm
  Diabetic kidney disease
  Endometriosis
  Epithelial ovarian cancer
  Esophageal squamous cell carcinoma
  Glioma
  Hepatocellular carcinoma
  HIV infectious disease
  Inherited bleeding disorder, platelet-type
  Intellectual disability
  Lung cancer
  Lung carcinoma
  Metastatic malignant neoplasm
  Nasopharyngeal carcinoma
  Neoplasm
  Neuroblastoma
  Non-insulin dependent diabetes
  Non-small-cell lung cancer
  Ovarian cancer
  Ovarian neoplasm
  Rheumatoid arthritis
  Temporal lobe epilepsy
  Uterine fibroids
  Asthma
  Gastric cancer
  Stomach cancer
  Melanoma
  Schizophrenia
  Undifferentiated carcinoma
  Adult glioblastoma
  Alzheimer disease
  Glioblastoma multiforme
  Pancreatic cancer
  Prostate cancer
  Prostate carcinoma
  Thrombocytopenia
• UniProt ID: CDC42_HUMAN
• PDB ID: 1A4R ; 1AJE ; 1AM4 ; 1AN0 ; 1CEE ; 1CF4 ; 1DOA ; 1E0A ; 1EES ; 1GRN ; 1GZS ; 1KI1 ; 1KZ7 ; 1KZG ; 1NF3 ; 2ASE ; 2DFK ; 2KB0 ; 2NGR ; 2ODB ; 2QRZ ; 2WM9 ; 2WMN ; 2WMO ; 3GCG ; 3QBV ; 3VHL ; 4DID ; 4ITR ; 4JS0 ; 4YC7 ; 4YDH ; 5CJP ; 5FI1 ; 5HZK ; 5UPK ; 5UPL ; 6AJ4 ; 6AJL ; 6SIU ; 6SUP ; 6TKY ; 6TKZ ; 7S0Y ; 8I5F
• EC Number: 3.6.5.2
• Pfam ID: PF00071
• Sequence:
  MQTIKCVVVGDGAVGKTCLLISYTTNKFPSEYVPTVFDNYAVTVMIGGEPYTLGLFDTAG
  QEDYDRLRPLSYPQTDVFLVCFSVVSPSSFENVKEKWVPEITHHCPKTPFLLVGTQIDLR
  DDPSTIEKLAKNKQKPITPETAEKLARDLKAVKYVECSALTQKGLKNVFDEAILAALEPP
  EPKKSRRCVLL
• Function: Plasma membrane-associated small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state. In active state binds to a variety of effector proteins to regulate cellular responses. Involved in epithelial cell polarization processes. Regulates the bipolar attachment of spindle microtubules to kinetochores before chromosome congression in metaphase. Regulates cell migration. In neurons, plays a role in the extension and maintenance of the formation of filopodia, thin and actin-rich surface projections. Required for DOCK10-mediated spine formation in Purkinje cells and hippocampal neurons. In podocytes, facilitates filopodia and podosomes formation upon DOCK11-activation. Upon activation by CaMKII, modulates dendritic spine structural plasticity by relaying CaMKII transient activation to synapse-specific, long-term signaling. Also plays a role in phagocytosis through organization of the F-actin cytoskeleton associated with forming phagocytic cups.
• KEGG Pathway:
  MAPK sig.ling pathway (hsa04010)
  Ras sig.ling pathway (hsa04014)
  Rap1 sig.ling pathway (hsa04015)
  Chemokine sig.ling pathway (hsa04062)
  Endocytosis (hsa04144)
  Axon guidance (hsa04360)
  VEGF sig.ling pathway (hsa04370)
  Focal adhesion (hsa04510)
  Adherens junction (hsa04520)
  Tight junction (hsa04530)
  T cell receptor sig.ling pathway (hsa04660)
  Fc gamma R-mediated phagocytosis (hsa04666)
  Leukocyte transendothelial migration (hsa04670)
  Neurotrophin sig.ling pathway (hsa04722)
  Regulation of actin cytoskeleton (hsa04810)
  GnRH sig.ling pathway (hsa04912)
  Non-alcoholic fatty liver disease (hsa04932)
  AGE-RAGE sig.ling pathway in diabetic complications (hsa04933)
  Bacterial invasion of epithelial cells (hsa05100)
  Epithelial cell sig.ling in Helicobacter pylori infection (hsa05120)
  Pathogenic Escherichia coli infection (hsa05130)
  Shigellosis (hsa05131)
  Salmonella infection (hsa05132)
  Yersinia infection (hsa05135)
  Human papillomavirus infection (hsa05165)
  Pathways in cancer (hsa05200)
  Viral carcinogenesis (hsa05203)
  Proteoglycans in cancer (hsa05205)
  Re.l cell carcinoma (hsa05211)
  Pancreatic cancer (hsa05212)
  Lipid and atherosclerosis (hsa05417)
• Reactome Pathway:
  EGFR downregulation (R-HSA-182971)
  Regulation of actin dynamics for phagocytic cup formation (R-HSA-2029482)
  CD28 dependent Vav1 pathway (R-HSA-389359)
  EPHB-mediated forward signaling (R-HSA-3928662)
  DCC mediated attractive signaling (R-HSA-418885)
  Inactivation of CDC42 and RAC1 (R-HSA-428543)
  VEGFA-VEGFR2 Pathway (R-HSA-4420097)
  Myogenesis (R-HSA-525793)
  RHO GTPases activate KTN1 (R-HSA-5625970)
  RHO GTPases activate IQGAPs (R-HSA-5626467)
  RHO GTPases activate PAKs (R-HSA-5627123)
  RHO GTPases Activate WASPs and WAVEs (R-HSA-5663213)
  RHO GTPases Activate Formins (R-HSA-5663220)
  MAPK6/MAPK4 signaling (R-HSA-5687128)
  Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation (R-HSA-8950505)
  G beta (R-HSA-8964616)
  CDC42 GTPase cycle (R-HSA-9013148)
  RAC1 GTPase cycle (R-HSA-9013149)
  RAC2 GTPase cycle (R-HSA-9013404)
  RHOQ GTPase cycle (R-HSA-9013406)
  RHOG GTPase cycle (R-HSA-9013408)
  RHOJ GTPase cycle (R-HSA-9013409)
  RHOU GTPase cycle (R-HSA-9013420)
  RAC3 GTPase cycle (R-HSA-9013423)
  RHOV GTPase cycle (R-HSA-9013424)
  FCGR3A-mediated phagocytosis (R-HSA-9664422)
  Factors involved in megakaryocyte development and platelet production (R-HSA-983231)
  GPVI-mediated activation cascade (R-HSA-114604)

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome	DISDV6BC	Definitive	Autosomal dominant	[1]
Matthew-Wood syndrome	DISA7HR7	Definitive	Altered Expression	[2]
Adrenal gland cancer	DISNFZKJ	Strong	Biomarker	[3]
Adrenal gland neoplasm	DISFK7RF	Strong	Biomarker	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[5]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[6]
Carcinoma	DISH9F1N	Strong	Genetic Variation	[3]
Cervical cancer	DISFSHPF	Strong	Biomarker	[7]
Colon cancer	DISVC52G	Strong	Biomarker	[8]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[8]
Colorectal neoplasm	DISR1UCN	Strong	Altered Expression	[9]
Diabetic kidney disease	DISJMWEY	Strong	Biomarker	[10]
Endometriosis	DISX1AG8	Strong	Genetic Variation	[11]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[12]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[13]
Glioma	DIS5RPEH	Strong	Altered Expression	[14]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[15]
HIV infectious disease	DISO97HC	Strong	Biomarker	[16]
Inherited bleeding disorder, platelet-type	DISIUNXT	Strong	Biomarker	[17]
Intellectual disability	DISMBNXP	Strong	Biomarker	[17]
Lung cancer	DISCM4YA	Strong	Biomarker	[18]
Lung carcinoma	DISTR26C	Strong	Biomarker	[18]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[19]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Altered Expression	[20]
Neoplasm	DISZKGEW	Strong	Biomarker	[21]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[22]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[23]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[24]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[12]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[12]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[25]
Temporal lobe epilepsy	DISNOPXX	Strong	Biomarker	[26]
Uterine fibroids	DISBZRMJ	Strong	Genetic Variation	[27]
Asthma	DISW9QNS	moderate	Biomarker	[28]
Gastric cancer	DISXGOUK	moderate	Biomarker	[29]
Stomach cancer	DISKIJSX	moderate	Biomarker	[29]
Melanoma	DIS1RRCY	Disputed	Genetic Variation	[30]
Schizophrenia	DISSRV2N	Disputed	Biomarker	[31]
Undifferentiated carcinoma	DISIAZST	Disputed	Biomarker	[32]
Adult glioblastoma	DISVP4LU	Limited	Biomarker	[33]
Alzheimer disease	DISF8S70	Limited	Biomarker	[34]
Glioblastoma multiforme	DISK8246	Limited	Biomarker	[33]
Pancreatic cancer	DISJC981	Limited	Altered Expression	[2]
Prostate cancer	DISF190Y	Limited	Biomarker	[21]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[35]
Thrombocytopenia	DISU61YW	Limited	Genetic Variation	[36]

19 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 Cell division control protein 42 homolog (CDC42).	[37]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cell division control protein 42 homolog (CDC42).	[38]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Cell division control protein 42 homolog (CDC42).	[39]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Cell division control protein 42 homolog (CDC42).	[40]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Cell division control protein 42 homolog (CDC42).	[41]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Cell division control protein 42 homolog (CDC42).	[43]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Cell division control protein 42 homolog (CDC42).	[44]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Cell division control protein 42 homolog (CDC42).	[45]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Cell division control protein 42 homolog (CDC42).	[46]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Cell division control protein 42 homolog (CDC42).	[47]
Pioglitazone	DMKJ485	Approved	Pioglitazone decreases the expression of Cell division control protein 42 homolog (CDC42).	[48]
Lovastatin	DM9OZWQ	Approved	Lovastatin increases the expression of Cell division control protein 42 homolog (CDC42).	[49]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Cell division control protein 42 homolog (CDC42).	[50]
Guaiacol	DMN4E7T	Phase 3	Guaiacol decreases the expression of Cell division control protein 42 homolog (CDC42).	[51]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Cell division control protein 42 homolog (CDC42).	[53]
SB-431542	DM0YOXQ	Preclinical	SB-431542 increases the expression of Cell division control protein 42 homolog (CDC42).	[54]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Cell division control protein 42 homolog (CDC42).	[55]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Cell division control protein 42 homolog (CDC42).	[56]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Cell division control protein 42 homolog (CDC42).	[57]

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 Cell division control protein 42 homolog (CDC42).	[42]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Cell division control protein 42 homolog (CDC42).	[52]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PALMATINE	DMJCOKV	Investigative	PALMATINE affects the binding of Cell division control protein 42 homolog (CDC42).	[58]

References

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