Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYF5340)

• DOT Name: Glia-derived nexin (SERPINE2)
• Synonyms: GDN; Peptidase inhibitor 7; PI-7; Protease nexin 1; PN-1; Protease nexin I; Serpin E2
• Gene Name: SERPINE2
• Related Disease:
  Cerebral infarction
  Adenocarcinoma
  Adenoma
  Adult glioblastoma
  Advanced cancer
  Alzheimer disease
  Astrocytoma
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Coeliac disease
  Colorectal carcinoma
  Colorectal neoplasm
  Coronary atherosclerosis
  Coronary heart disease
  Cystic fibrosis
  Esophageal squamous cell carcinoma
  Gastric cancer
  Glioblastoma multiforme
  Haemophilia A
  Hepatitis B virus infection
  Inflammatory bowel disease
  Intervertebral disc degeneration
  Metastatic malignant neoplasm
  Neoplasm
  Neuroblastoma
  Non-insulin dependent diabetes
  Oral cavity squamous cell carcinoma
  Osteoarthritis
  Pancreatic tumour
  Prostate adenocarcinoma
  Prostate neoplasm
  Pulmonary emphysema
  Pulmonary fibrosis
  Scleroderma
  Squamous cell carcinoma
  Ulcerative colitis
  Bone osteosarcoma
  Head-neck squamous cell carcinoma
  Osteosarcoma
  Systemic sclerosis
  Asthma
  Diabetic neuropathy
  High blood pressure
  Stomach cancer
  Thyroid gland papillary carcinoma
  Thyroid tumor
• UniProt ID: GDN_HUMAN
• PDB ID: 4DY0; 4DY7
• Pfam ID: PF00079
• Sequence:
  MNWHLPLFLLASVTLPSICSHFNPLSLEELGSNTGIQVFNQIVKSRPHDNIVISPHGIAS
  VLGMLQLGADGRTKKQLAMVMRYGVNGVGKILKKINKAIVSKKNKDIVTVANAVFVKNAS
  EIEVPFVTRNKDVFQCEVRNVNFEDPASACDSINAWVKNETRDMIDNLLSPDLIDGVLTR
  LVLVNAVYFKGLWKSRFQPENTKKRTFVAADGKSYQVPMLAQLSVFRCGSTSAPNDLWYN
  FIELPYHGESISMLIALPTESSTPLSAIIPHISTKTIDSWMSIMVPKRVQVILPKFTAVA
  QTDLKEPLKVLGITDMFDSSKANFAKITTGSENLHVSHILQKAKIEVSEDGTKASAATTA
  ILIARSSPPWFIVDRPFLFFIRHNPTGAVLFMGQINKP
• Function: Serine protease inhibitor with activity toward thrombin, trypsin, and urokinase. Promotes neurite extension by inhibiting thrombin. Binds heparin.
• KEGG Pathway: Complement and coagulation cascades (hsa04610)
• Reactome Pathway:
  Common Pathway of Fibrin Clot Formation (R-HSA-140875)
  Dissolution of Fibrin Clot (R-HSA-75205)
  Intrinsic Pathway of Fibrin Clot Formation (R-HSA-140837)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cerebral infarction	DISR1WNP	Definitive	Genetic Variation	[1]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[2]
Adenoma	DIS78ZEV	Strong	Altered Expression	[3]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[4]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[5]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[6]
Astrocytoma	DISL3V18	Strong	Altered Expression	[7]
Breast cancer	DIS7DPX1	Strong	Biomarker	[8]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[8]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[9]
Coeliac disease	DISIY60C	Strong	Genetic Variation	[10]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[11]
Colorectal neoplasm	DISR1UCN	Strong	Altered Expression	[3]
Coronary atherosclerosis	DISKNDYU	Strong	Biomarker	[12]
Coronary heart disease	DIS5OIP1	Strong	Biomarker	[12]
Cystic fibrosis	DIS2OK1Q	Strong	Altered Expression	[13]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[14]
Gastric cancer	DISXGOUK	Strong	Biomarker	[15]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[4]
Haemophilia A	DIS0RQ2E	Strong	Biomarker	[16]
Hepatitis B virus infection	DISLQ2XY	Strong	Altered Expression	[17]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[18]
Intervertebral disc degeneration	DISG3AIM	Strong	Altered Expression	[19]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[14]
Neoplasm	DISZKGEW	Strong	Biomarker	[20]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[4]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[12]
Oral cavity squamous cell carcinoma	DISQVJVA	Strong	Altered Expression	[21]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[22]
Pancreatic tumour	DIS3U0LK	Strong	Biomarker	[23]
Prostate adenocarcinoma	DISBZYU8	Strong	Biomarker	[24]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[25]
Pulmonary emphysema	DIS5M7HZ	Strong	Genetic Variation	[26]
Pulmonary fibrosis	DISQKVLA	Strong	Biomarker	[27]
Scleroderma	DISVQ342	Strong	Biomarker	[28]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[29]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[30]
Bone osteosarcoma	DIST1004	moderate	Altered Expression	[31]
Head-neck squamous cell carcinoma	DISF7P24	moderate	Genetic Variation	[32]
Osteosarcoma	DISLQ7E2	moderate	Altered Expression	[31]
Systemic sclerosis	DISF44L6	moderate	Genetic Variation	[33]
Asthma	DISW9QNS	Limited	Biomarker	[34]
Diabetic neuropathy	DISX6VF8	Limited	Altered Expression	[35]
High blood pressure	DISY2OHH	Limited	Biomarker	[36]
Stomach cancer	DISKIJSX	Limited	Biomarker	[37]
Thyroid gland papillary carcinoma	DIS48YMM	Limited	Biomarker	[38]
Thyroid tumor	DISLVKMD	Limited	Biomarker	[38]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Glia-derived nexin (SERPINE2) increases the Neutropenia ADR of Fluorouracil.	[73]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Glia-derived nexin (SERPINE2).	[39]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Glia-derived nexin (SERPINE2).	[61]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Glia-derived nexin (SERPINE2).	[65]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Glia-derived nexin (SERPINE2).	[40]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Glia-derived nexin (SERPINE2).	[41]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Glia-derived nexin (SERPINE2).	[42]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Glia-derived nexin (SERPINE2).	[43]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Glia-derived nexin (SERPINE2).	[44]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Glia-derived nexin (SERPINE2).	[45]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Glia-derived nexin (SERPINE2).	[46]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Glia-derived nexin (SERPINE2).	[47]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Glia-derived nexin (SERPINE2).	[48]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Glia-derived nexin (SERPINE2).	[49]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Glia-derived nexin (SERPINE2).	[50]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Glia-derived nexin (SERPINE2).	[51]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Glia-derived nexin (SERPINE2).	[52]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Glia-derived nexin (SERPINE2).	[53]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Glia-derived nexin (SERPINE2).	[54]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Glia-derived nexin (SERPINE2).	[55]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Glia-derived nexin (SERPINE2).	[56]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Glia-derived nexin (SERPINE2).	[57]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Glia-derived nexin (SERPINE2).	[58]
Mitotane	DMU1GX0	Approved	Mitotane increases the expression of Glia-derived nexin (SERPINE2).	[59]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Glia-derived nexin (SERPINE2).	[60]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Glia-derived nexin (SERPINE2).	[62]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Glia-derived nexin (SERPINE2).	[63]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Glia-derived nexin (SERPINE2).	[64]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Glia-derived nexin (SERPINE2).	[66]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Glia-derived nexin (SERPINE2).	[67]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Glia-derived nexin (SERPINE2).	[68]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Glia-derived nexin (SERPINE2).	[69]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Glia-derived nexin (SERPINE2).	[70]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine decreases the expression of Glia-derived nexin (SERPINE2).	[71]
Cycloheximide	DMGDA3C	Investigative	Cycloheximide increases the expression of Glia-derived nexin (SERPINE2).	[72]

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