Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLVNZ8U)

• DOT Name: Fibulin-5 (FBLN5)
• Synonyms: FIBL-5; Developmental arteries and neural crest EGF-like protein; Dance; Urine p50 protein; UP50
• Gene Name: FBLN5
• Related Disease:
  Breast cancer
  Breast carcinoma
  Crohn disease
  Cutis laxa, autosomal dominant 2
  Inflammatory bowel disease
  Ulcerative colitis
  Advanced cancer
  Bladder cancer
  Blindness
  Cardiac failure
  Cardiovascular disease
  Charcot marie tooth disease
  Charcot-Marie-Tooth disease, demyelinating, IIA 1H
  Colorectal carcinoma
  Congestive heart failure
  Cutis laxa, autosomal recessive, type 1A
  Demyelinating polyneuropathy
  Epithelial ovarian cancer
  Hepatocellular carcinoma
  Lung neoplasm
  Metastatic malignant neoplasm
  Nasopharyngeal carcinoma
  Neoplasm
  Non-small-cell lung cancer
  Ovarian cancer
  Ovarian neoplasm
  Peripheral neuropathy
  Prostate cancer
  Prostate neoplasm
  Pulmonary fibrosis
  Pulmonary hypertension
  Respiratory failure
  Type-1/2 diabetes
  Urinary bladder cancer
  Urinary bladder neoplasm
  Vascular disease
  Chronic obstructive pulmonary disease
  Demyelinating hereditary motor and sensory neuropathy
  Macular degeneration, age-related, 3
  Peripheral arterial disease
  Pulmonary emphysema
  Autosomal dominant cutis laxa
  Autosomal recessive cutis laxa type 1
  Hereditary sensorimotor neuropathy with hyperelastic skin
  OPTN-related open angle glaucoma
  Adult respiratory distress syndrome
  Aortic aneurysm
  Lung cancer
  Lung carcinoma
  Marfan syndrome
• UniProt ID: FBLN5_HUMAN
• Pfam ID: PF12662 ; PF07645
• Sequence:
  MPGIKRILTVTILALCLPSPGNAQAQCTNGFDLDRQSGQCLDIDECRTIPEACRGDMMCV
  NQNGGYLCIPRTNPVYRGPYSNPYSTPYSGPYPAAAPPLSAPNYPTISRPLICRFGYQMD
  ESNQCVDVDECATDSHQCNPTQICINTEGGYTCSCTDGYWLLEGQCLDIDECRYGYCQQL
  CANVPGSYSCTCNPGFTLNEDGRSCQDVNECATENPCVQTCVNTYGSFICRCDPGYELEE
  DGVHCSDMDECSFSEFLCQHECVNQPGTYFCSCPPGYILLDDNRSCQDINECEHRNHTCN
  LQQTCYNLQGGFKCIDPIRCEEPYLRISDNRCMCPAENPGCRDQPFTILYRDMDVVSGRS
  VPADIFQMQATTRYPGAYYIFQIKSGNEGREFYMRQTGPISATLVMTRPIKGPREIQLDL
  EMITVNTVINFRGSSVIRLRIYVSQYPF
• Function: Essential for elastic fiber formation, is involved in the assembly of continuous elastin (ELN) polymer and promotes the interaction of microfibrils and ELN. Stabilizes and organizes elastic fibers in the skin, lung and vasculature. Promotes adhesion of endothelial cells through interaction of integrins and the RGD motif. Vascular ligand for integrin receptors which may play a role in vascular development and remodeling. May act as an adapter that mediates the interaction between FBN1 and ELN.
• Tissue Specificity: Expressed in skin fibroblasts (at protein level). Expressed predominantly in heart, ovary, and colon but also in kidney, pancreas, testis, lung and placenta. Not detectable in brain, liver, thymus, prostate, or peripheral blood leukocytes .
• Reactome Pathway:
  Molecules associated with elastic fibres (R-HSA-2129379)
  Elastic fibre formation (R-HSA-1566948)

Molecular Interaction Atlas (MIA) of This DOT

50 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Definitive	Biomarker	[1]
Breast carcinoma	DIS2UE88	Definitive	Biomarker	[1]
Crohn disease	DIS2C5Q8	Definitive	Biomarker	[2]
Cutis laxa, autosomal dominant 2	DIS2GJOK	Definitive	Autosomal dominant	[3]
Inflammatory bowel disease	DISGN23E	Definitive	Biomarker	[2]
Ulcerative colitis	DIS8K27O	Definitive	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Bladder cancer	DISUHNM0	Strong	Altered Expression	[5]
Blindness	DISTIM10	Strong	Genetic Variation	[6]
Cardiac failure	DISDC067	Strong	Biomarker	[7]
Cardiovascular disease	DIS2IQDX	Strong	Altered Expression	[8]
Charcot marie tooth disease	DIS3BT2L	Strong	Biomarker	[9]
Charcot-Marie-Tooth disease, demyelinating, IIA 1H	DISVPV9N	Strong	Autosomal dominant	[9]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[10]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[7]
Cutis laxa, autosomal recessive, type 1A	DISKDUOX	Strong	Autosomal recessive	[11]
Demyelinating polyneuropathy	DIS7IO4W	Strong	Genetic Variation	[12]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[13]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[14]
Lung neoplasm	DISVARNB	Strong	Altered Expression	[15]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[16]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Altered Expression	[16]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Genetic Variation	[17]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[18]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[18]
Peripheral neuropathy	DIS7KN5G	Strong	Genetic Variation	[9]
Prostate cancer	DISF190Y	Strong	Biomarker	[19]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[19]
Pulmonary fibrosis	DISQKVLA	Strong	Biomarker	[20]
Pulmonary hypertension	DIS1RSP5	Strong	Biomarker	[7]
Respiratory failure	DISVMYJO	Strong	Biomarker	[7]
Type-1/2 diabetes	DISIUHAP	Strong	Altered Expression	[8]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[5]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[5]
Vascular disease	DISVS67S	Strong	Biomarker	[7]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Altered Expression	[21]
Demyelinating hereditary motor and sensory neuropathy	DISZTO2L	Moderate	Autosomal dominant	[22]
Macular degeneration, age-related, 3	DIS9UNRM	Moderate	Autosomal dominant	[23]
Peripheral arterial disease	DIS78WFB	moderate	Biomarker	[24]
Pulmonary emphysema	DIS5M7HZ	moderate	Genetic Variation	[25]
Autosomal dominant cutis laxa	DIS2180B	Supportive	Autosomal dominant	[26]
Autosomal recessive cutis laxa type 1	DIS27S03	Supportive	Autosomal recessive	[27]
Hereditary sensorimotor neuropathy with hyperelastic skin	DISO2E2T	Supportive	Autosomal dominant	[9]
OPTN-related open angle glaucoma	DISDR98A	Disputed	Biomarker	[28]
Adult respiratory distress syndrome	DISIJV47	Limited	Biomarker	[29]
Aortic aneurysm	DISQ5KRA	Limited	Biomarker	[30]
Lung cancer	DISCM4YA	Limited	Posttranslational Modification	[17]
Lung carcinoma	DISTR26C	Limited	Posttranslational Modification	[17]
Marfan syndrome	DISVEUWZ	Limited	Biomarker	[31]

1 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 Fibulin-5 (FBLN5).	[32]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Fibulin-5 (FBLN5).	[33]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Fibulin-5 (FBLN5).	[34]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Fibulin-5 (FBLN5).	[35]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Fibulin-5 (FBLN5).	[36]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Fibulin-5 (FBLN5).	[37]
Selenium	DM25CGV	Approved	Selenium increases the expression of Fibulin-5 (FBLN5).	[38]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Fibulin-5 (FBLN5).	[39]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Fibulin-5 (FBLN5).	[40]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Fibulin-5 (FBLN5).	[41]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Fibulin-5 (FBLN5).	[42]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Fibulin-5 (FBLN5).	[43]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Fibulin-5 (FBLN5).	[44]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Fibulin-5 (FBLN5).	[45]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Fibulin-5 (FBLN5).	[46]
Nitrobenzanthrone	DMN6L70	Investigative	Nitrobenzanthrone increases the expression of Fibulin-5 (FBLN5).	[47]

References

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