Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZVKG8A)

• DOT Name: Drebrin (DBN1)
• Synonyms: Developmentally-regulated brain protein
• Gene Name: DBN1
• Related Disease:
  Angle-closure glaucoma
  Glaucoma/ocular hypertension
  OPTN-related open angle glaucoma
  Primary angle-closure glaucoma
  Advanced cancer
  Alzheimer disease
  Arteriosclerosis
  Atherosclerosis
  Bipolar disorder
  Bladder cancer
  Carcinoma
  Dementia
  Glioblastoma multiforme
  Glioma
  Non-small-cell lung cancer
  Opioid dependence
  Parkinson disease
  Prostate cancer
  Prostate carcinoma
  Schizophrenia
  Sciatic neuropathy
  Temporal lobe epilepsy
  Urinary bladder cancer
  Urinary bladder neoplasm
  Colon cancer
  Colon carcinoma
  Neoplasm
  Cognitive impairment
  Intellectual disability
  Nervous system disease
• UniProt ID: DREB_HUMAN
• PDB ID: 5Y1Z; 5ZZ9
• Pfam ID: PF00241
• Sequence:
  MAGVSFSGHRLELLAAYEEVIREESAADWALYTYEDGSDDLKLAASGEGGLQELSGHFEN
  QKVMYGFCSVKDSQAALPKYVLINWVGEDVPDARKCACASHVAKVAEFFQGVDVIVNASS
  VEDIDAGAIGQRLSNGLARLSSPVLHRLRLREDENAEPVGTTYQKTDAAVEMKRINREQF
  WEQAKKEEELRKEEERKKALDERLRFEQERMEQERQEQEERERRYREREQQIEEHRRKQQ
  TLEAEEAKRRLKEQSIFGDHRDEEEETHMKKSESEVEEAAAIIAQRPDNPREFFKQQERV
  ASASAGSCDVPSPFNHRPGSHLDSHRRMAPTPIPTRSPSDSSTASTPVAEQIERALDEVT
  SSQPPPLPPPPPPAQETQEPSPILDSEETRAAAPQAWAGPMEEPPQAQAPPRGPGSPAED
  LMFMESAEQAVLAAPVEPATADATEIHDAADTIETDTATADTTVANNVPPAATSLIDLWP
  GNGEGASTLQGEPRAPTPPSGTEVTLAEVPLLDEVAPEPLLPAGEGCATLLNFDELPEPP
  ATFCDPEEVEGESLAAPQTPTLPSALEELEQEQEPEPHLLTNGETTQKEGTQASEGYFSQ
  SQEEEFAQSEELCAKAPPPVFYNKPPEIDITCWDADPVPEEEEGFEGGD
• Function: Actin cytoskeleton-organizing protein that plays a role in the formation of cell projections. Required for actin polymerization at immunological synapses (IS) and for the recruitment of the chemokine receptor CXCR4 to IS. Plays a role in dendritic spine morphogenesis and organization, including the localization of the dopamine receptor DRD1 to the dendritic spines. Involved in memory-related synaptic plasticity in the hippocampus.
• Tissue Specificity: Expressed in the brain, with expression in the molecular layer of the dentate gyrus, stratum pyramidale, and stratum radiatum of the hippocampus (at protein level) . Also expressed in the terminal varicosities distributed along dendritic trees of pyramidal cells in CA4 and CA3 of the hippocampus (at protein level) . Expressed in pyramidal cells in CA2, CA1 and the subiculum of the hippocampus (at protein level) . Expressed in peripheral blood lymphocytes, including T-cells (at protein level) . Expressed in the brain . Expressed in the heart, placenta, lung, skeletal muscle, kidney, pancreas, skin fibroblasts, gingival fibroblasts and bone-derived cells (Ref.2).
• Reactome Pathway:
  RHOH GTPase cycle (R-HSA-9013407)
  RHOBTB2 GTPase cycle (R-HSA-9013418)
  RHOBTB1 GTPase cycle (R-HSA-9013422)
  RHOD GTPase cycle (R-HSA-9013405)

Molecular Interaction Atlas (MIA) of This DOT

30 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Angle-closure glaucoma	DISZ95KY	Definitive	Altered Expression	[1]
Glaucoma/ocular hypertension	DISLBXBY	Definitive	Biomarker	[1]
OPTN-related open angle glaucoma	DISDR98A	Definitive	Altered Expression	[1]
Primary angle-closure glaucoma	DISX8UKZ	Definitive	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Arteriosclerosis	DISK5QGC	Strong	Altered Expression	[4]
Atherosclerosis	DISMN9J3	Strong	Altered Expression	[4]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[5]
Bladder cancer	DISUHNM0	Strong	Altered Expression	[6]
Carcinoma	DISH9F1N	Strong	Biomarker	[7]
Dementia	DISXL1WY	Strong	Altered Expression	[8]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[9]
Glioma	DIS5RPEH	Strong	Altered Expression	[9]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[10]
Opioid dependence	DIS6WEHK	Strong	Biomarker	[11]
Parkinson disease	DISQVHKL	Strong	Therapeutic	[12]
Prostate cancer	DISF190Y	Strong	Biomarker	[2]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[2]
Schizophrenia	DISSRV2N	Strong	Biomarker	[13]
Sciatic neuropathy	DISMGDKX	Strong	Biomarker	[14]
Temporal lobe epilepsy	DISNOPXX	Strong	Biomarker	[15]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[6]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[6]
Colon cancer	DISVC52G	moderate	Altered Expression	[16]
Colon carcinoma	DISJYKUO	moderate	Altered Expression	[16]
Neoplasm	DISZKGEW	moderate	Altered Expression	[16]
Cognitive impairment	DISH2ERD	Limited	Biomarker	[17]
Intellectual disability	DISMBNXP	Limited	Biomarker	[18]
Nervous system disease	DISJ7GGT	Limited	Biomarker	[19]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Drebrin (DBN1) affects the response to substance of Methotrexate.	[43]
Etoposide	DMNH3PG	Approved	Drebrin (DBN1) affects the response to substance of Etoposide.	[43]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Drebrin (DBN1).	[20]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Drebrin (DBN1).	[39]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Drebrin (DBN1).	[40]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Drebrin (DBN1).	[39]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid increases the phosphorylation of Drebrin (DBN1).	[42]

21 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 Drebrin (DBN1).	[21]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Drebrin (DBN1).	[22]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Drebrin (DBN1).	[23]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Drebrin (DBN1).	[24]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Drebrin (DBN1).	[25]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Drebrin (DBN1).	[26]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Drebrin (DBN1).	[27]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Drebrin (DBN1).	[28]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Drebrin (DBN1).	[29]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Drebrin (DBN1).	[30]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Drebrin (DBN1).	[31]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Drebrin (DBN1).	[32]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Drebrin (DBN1).	[33]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Drebrin (DBN1).	[34]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Drebrin (DBN1).	[35]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Drebrin (DBN1).	[36]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Drebrin (DBN1).	[37]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Drebrin (DBN1).	[38]
PIRINIXIC ACID	DM82Y75	Preclinical	PIRINIXIC ACID increases the expression of Drebrin (DBN1).	[35]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Drebrin (DBN1).	[26]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Drebrin (DBN1).	[41]

References

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