Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6RKLI9)

• DOT Name: Fibrinogen beta chain (FGB)
• Gene Name: FGB
• Related Disease:
  Cerebrovascular disease
  Congenital fibrinogen deficiency
  Familial hypercholesterolemia
  Hypercholesterolemia, familial, 1
  Non-insulin dependent diabetes
  Acute coronary syndrome
  Acute myocardial infarction
  Arteriosclerosis
  Atherosclerosis
  Atrial fibrillation
  Cardiovascular disease
  Carotid artery disease
  Cerebral infarction
  Chronic renal failure
  Colorectal carcinoma
  Congenital afibrinogenemia
  End-stage renal disease
  Factor VII deficiency
  High blood pressure
  Inflammatory bowel disease
  Legg-Calve-Perthes disease
  Lupus nephritis
  Myocardial infarction
  Myocardial ischemia
  Osteoporosis
  Pancreatitis
  Parkinson disease
  Peripheral arterial disease
  Peripheral vascular disease
  Pulmonary embolism
  Rheumatoid arthritis
  Stroke
  Thrombophilia
  Vascular disease
  Clear cell renal carcinoma
  Periodontal disease
  Periodontitis
  Renal cell carcinoma
  Type-1 diabetes
  Familial dysfibrinogenemia
  Familial hypofibrinogenemia
  Gastric cancer
  Hyperglycemia
  Stomach cancer
  Thrombosis
  Type-1/2 diabetes
• UniProt ID: FIBB_HUMAN
• PDB ID: 1FZA ; 1FZB ; 1FZC ; 1FZE ; 1FZF ; 1FZG ; 1LT9 ; 1LTJ ; 1N86 ; 1N8E ; 1RE3 ; 1RE4 ; 1RF0 ; 1RF1 ; 2A45 ; 2FFD ; 2H43 ; 2HLO ; 2HOD ; 2HPC ; 2OYH ; 2OYI ; 2Q9I ; 2XNX ; 2XNY ; 2Z4E ; 3BVH ; 3E1I ; 3GHG ; 3H32 ; 3HUS ; 6ATZ ; 6BIJ ; 6BIL ; 6V0Y ; 6V13 ; 6V15 ; 6V18 ; 6V19 ; 6V1A
• Pfam ID: PF08702 ; PF00147
• Sequence:
  MKRMVSWSFHKLKTMKHLLLLLLCVFLVKSQGVNDNEEGFFSARGHRPLDKKREEAPSLR
  PAPPPISGGGYRARPAKAAATQKKVERKAPDAGGCLHADPDLGVLCPTGCQLQEALLQQE
  RPIRNSVDELNNNVEAVSQTSSSSFQYMYLLKDLWQKRQKQVKDNENVVNEYSSELEKHQ
  LYIDETVNSNIPTNLRVLRSILENLRSKIQKLESDVSAQMEYCRTPCTVSCNIPVVSGKE
  CEEIIRKGGETSEMYLIQPDSSVKPYRVYCDMNTENGGWTVIQNRQDGSVDFGRKWDPYK
  QGFGNVATNTDGKNYCGLPGEYWLGNDKISQLTRMGPTELLIEMEDWKGDKVKAHYGGFT
  VQNEANKYQISVNKYRGTAGNALMDGASQLMGENRTMTIHNGMFFSTYDRDNDGWLTSDP
  RKQCSKEDGGGWWYNRCHAANPNGRYYWGGQYTWDMAKHGTDDGVVWMNWKGSWYSMRKM
  SMKIRPFFPQQ
• Function: Cleaved by the protease thrombin to yield monomers which, together with fibrinogen alpha (FGA) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in hemostasis as one of the primary components of blood clots. In addition, functions during the early stages of wound repair to stabilize the lesion and guide cell migration during re-epithelialization. Was originally thought to be essential for platelet aggregation, based on in vitro studies using anticoagulated blood. However subsequent studies have shown that it is not absolutely required for thrombus formation in vivo. Enhances expression of SELP in activated platelets. Maternal fibrinogen is essential for successful pregnancy. Fibrin deposition is also associated with infection, where it protects against IFNG-mediated hemorrhage. May also facilitate the antibacterial immune response via both innate and T-cell mediated pathways.
• Tissue Specificity: Detected in blood plasma (at protein level).
• KEGG Pathway:
  Complement and coagulation cascades (hsa04610)
  Platelet activation (hsa04611)
  Neutrophil extracellular trap formation (hsa04613)
  Coro.virus disease - COVID-19 (hsa05171)
• Reactome Pathway:
  ER-Phagosome pathway (R-HSA-1236974)
  Common Pathway of Fibrin Clot Formation (R-HSA-140875)
  MyD88 (R-HSA-166058)
  Integrin cell surface interactions (R-HSA-216083)
  Integrin signaling (R-HSA-354192)
  GRB2 (R-HSA-354194)
  p130Cas linkage to MAPK signaling for integrins (R-HSA-372708)
  MyD88 deficiency (TLR2/4) (R-HSA-5602498)
  IRAK4 deficiency (TLR2/4) (R-HSA-5603041)
  MAP2K and MAPK activation (R-HSA-5674135)
  Regulation of TLR by endogenous ligand (R-HSA-5686938)
  Signaling by moderate kinase activity BRAF mutants (R-HSA-6802946)
  Signaling by high-kinase activity BRAF mutants (R-HSA-6802948)
  Signaling by BRAF and RAF1 fusions (R-HSA-6802952)
  Paradoxical activation of RAF signaling by kinase inactive BRAF (R-HSA-6802955)
  Signaling downstream of RAS mutants (R-HSA-9649948)
  Signaling by RAF1 mutants (R-HSA-9656223)
  Platelet degranulation (R-HSA-114608)
• BioCyc Pathway: MetaCyc:ENSG00000171564-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cerebrovascular disease	DISAB237	Definitive	Genetic Variation	[1]
Congenital fibrinogen deficiency	DIS84ZAR	Definitive	Semidominant	[2]
Familial hypercholesterolemia	DISC06IX	Definitive	Genetic Variation	[3]
Hypercholesterolemia, familial, 1	DISU411W	Definitive	Genetic Variation	[3]
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Genetic Variation	[4]
Acute coronary syndrome	DIS7DYEW	Strong	Genetic Variation	[5]
Acute myocardial infarction	DISE3HTG	Strong	Genetic Variation	[6]
Arteriosclerosis	DISK5QGC	Strong	Altered Expression	[7]
Atherosclerosis	DISMN9J3	Strong	Altered Expression	[7]
Atrial fibrillation	DIS15W6U	Strong	Genetic Variation	[8]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[9]
Carotid artery disease	DISLRVLT	Strong	Biomarker	[10]
Cerebral infarction	DISR1WNP	Strong	Genetic Variation	[11]
Chronic renal failure	DISGG7K6	Strong	Genetic Variation	[12]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[13]
Congenital afibrinogenemia	DISGCW8D	Strong	Autosomal recessive	[14]
End-stage renal disease	DISXA7GG	Strong	Genetic Variation	[12]
Factor VII deficiency	DISKZWAG	Strong	Genetic Variation	[15]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[16]
Inflammatory bowel disease	DISGN23E	Strong	Genetic Variation	[17]
Legg-Calve-Perthes disease	DISE7BRZ	Strong	Genetic Variation	[18]
Lupus nephritis	DISCVGPZ	Strong	Biomarker	[19]
Myocardial infarction	DIS655KI	Strong	Genetic Variation	[20]
Myocardial ischemia	DISFTVXF	Strong	Genetic Variation	[21]
Osteoporosis	DISF2JE0	Strong	Biomarker	[22]
Pancreatitis	DIS0IJEF	Strong	Biomarker	[23]
Parkinson disease	DISQVHKL	Strong	Biomarker	[24]
Peripheral arterial disease	DIS78WFB	Strong	Genetic Variation	[25]
Peripheral vascular disease	DISXSU1Y	Strong	Genetic Variation	[25]
Pulmonary embolism	DISJYP9B	Strong	Biomarker	[26]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[27]
Stroke	DISX6UHX	Strong	Genetic Variation	[28]
Thrombophilia	DISQR7U7	Strong	Autosomal dominant	[29]
Vascular disease	DISVS67S	Strong	Biomarker	[30]
Clear cell renal carcinoma	DISBXRFJ	moderate	Altered Expression	[31]
Periodontal disease	DISJQHVN	moderate	Genetic Variation	[32]
Periodontitis	DISI9JOI	moderate	Genetic Variation	[32]
Renal cell carcinoma	DISQZ2X8	moderate	Altered Expression	[31]
Type-1 diabetes	DIS7HLUB	moderate	Genetic Variation	[33]
Familial dysfibrinogenemia	DISEOPCW	Supportive	Autosomal dominant	[34]
Familial hypofibrinogenemia	DIS7WFBL	Supportive	Autosomal dominant	[35]
Gastric cancer	DISXGOUK	Limited	Biomarker	[36]
Hyperglycemia	DIS0BZB5	Limited	Genetic Variation	[37]
Stomach cancer	DISKIJSX	Limited	Biomarker	[36]
Thrombosis	DIS2TXP8	Limited	Biomarker	[38]
Type-1/2 diabetes	DISIUHAP	Limited	Genetic Variation	[37]

13 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 Fibrinogen beta chain (FGB).	[39]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Fibrinogen beta chain (FGB).	[40]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Fibrinogen beta chain (FGB).	[41]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Fibrinogen beta chain (FGB).	[42]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Fibrinogen beta chain (FGB).	[43]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Fibrinogen beta chain (FGB).	[44]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Fibrinogen beta chain (FGB).	[45]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Fibrinogen beta chain (FGB).	[46]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of Fibrinogen beta chain (FGB).	[48]
LY2835219	DM93VBZ	Approved	LY2835219 decreases the expression of Fibrinogen beta chain (FGB).	[49]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Fibrinogen beta chain (FGB).	[51]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Fibrinogen beta chain (FGB).	[52]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Fibrinogen beta chain (FGB).	[53]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Aspirin	DM672AH	Approved	Aspirin decreases the secretion of Fibrinogen beta chain (FGB).	[47]
adenosine diphosphate	DMFUHKP	Investigative	adenosine diphosphate decreases the secretion of Fibrinogen beta chain (FGB).	[47]

1 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 Fibrinogen beta chain (FGB).	[50]

References

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