Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5RDUFO)

• DOT Name: Leukocyte elastase inhibitor (SERPINB1)
• Synonyms: LEI; Monocyte/neutrophil elastase inhibitor; EI; M/NEI; Peptidase inhibitor 2; PI-2; Serpin B1
• Gene Name: SERPINB1
• Related Disease:
  Acute gouty arthritis
  Adult glioblastoma
  Alzheimer disease
  Amyloidosis
  Aniridia
  Breast carcinoma
  Bronchopulmonary dysplasia
  Cohen syndrome
  Congenital alveolar dysplasia
  Glioblastoma multiforme
  Glioma
  Hepatocellular carcinoma
  Leukopenia
  Metabolic disorder
  Pneumonia
  Pneumonitis
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Psoriasis
  Pulmonary disease
  Systemic lupus erythematosus
  Type-1/2 diabetes
  Breast cancer
  Neoplasm
• UniProt ID: ILEU_HUMAN
• PDB ID: 4GA7
• Pfam ID: PF00079
• Sequence:
  MEQLSSANTRFALDLFLALSENNPAGNIFISPFSISSAMAMVFLGTRGNTAAQLSKTFHF
  NTVEEVHSRFQSLNADINKRGASYILKLANRLYGEKTYNFLPEFLVSTQKTYGADLASVD
  FQHASEDARKTINQWVKGQTEGKIPELLASGMVDNMTKLVLVNAIYFKGNWKDKFMKEAT
  TNAPFRLNKKDRKTVKMMYQKKKFAYGYIEDLKCRVLELPYQGEELSMVILLPDDIEDES
  TGLKKIEEQLTLEKLHEWTKPENLDFIEVNVSLPRFKLEESYTLNSDLARLGVQDLFNSS
  KADLSGMSGARDIFISKIVHKSFVEVNEEGTEAAAATAGIATFCMLMPEENFTADHPFLF
  FIRHNSSGSILFLGRFSSP
• Function: Neutrophil serine protease inhibitor that plays an essential role in the regulation of the innate immune response, inflammation and cellular homeostasis. Acts primarily to protect the cell from proteases released in the cytoplasm during stress or infection. These proteases are important in killing microbes but when released from granules, these potent enzymes also destroy host proteins and contribute to mortality. Regulates the activity of the neutrophil proteases elastase, cathepsin G, proteinase-3, chymase, chymotrypsin, and kallikrein-3. Acts also as a potent intracellular inhibitor of GZMH by directly blocking its proteolytic activity. During inflammation, limits the activity of inflammatory caspases CASP1, CASP4 and CASP5 by suppressing their caspase-recruitment domain (CARD) oligomerization and enzymatic activation. When secreted, promotes the proliferation of beta-cells via its protease inhibitory function.
• Tissue Specificity: In human bone marrow, present in all CD45+ populations. Expression levels are highest in the neutrophil lineage, intermediate in monocytic, and lowest in lymphocytic lineage. Within the neutrophil lineage, expression is highest in promyelocytes.
• Reactome Pathway: Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

25 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute gouty arthritis	DISY5UJH	Strong	Biomarker	[1]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[2]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[3]
Amyloidosis	DISHTAI2	Strong	Biomarker	[4]
Aniridia	DIS1P333	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[6]
Bronchopulmonary dysplasia	DISO0BY5	Strong	Biomarker	[7]
Cohen syndrome	DISOOFEZ	Strong	Altered Expression	[8]
Congenital alveolar dysplasia	DIS1IYUN	Strong	Biomarker	[9]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[2]
Glioma	DIS5RPEH	Strong	Biomarker	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[10]
Leukopenia	DISJMBMM	Strong	Biomarker	[8]
Metabolic disorder	DIS71G5H	Strong	Biomarker	[11]
Pneumonia	DIS8EF3M	Strong	Biomarker	[12]
Pneumonitis	DIS88E0K	Strong	Biomarker	[12]
Prostate cancer	DISF190Y	Strong	Biomarker	[13]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[13]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[13]
Psoriasis	DIS59VMN	Strong	Altered Expression	[14]
Pulmonary disease	DIS6060I	Strong	Altered Expression	[7]
Systemic lupus erythematosus	DISI1SZ7	Strong	Altered Expression	[15]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[11]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[6]
Neoplasm	DISZKGEW	Limited	Altered Expression	[16]

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	Leukocyte elastase inhibitor (SERPINB1) affects the response to substance of Temozolomide.	[40]
DTI-015	DMXZRW0	Approved	Leukocyte elastase inhibitor (SERPINB1) affects the response to substance of DTI-015.	[40]
Topotecan	DMP6G8T	Approved	Leukocyte elastase inhibitor (SERPINB1) affects the response to substance of Topotecan.	[41]

24 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 Leukocyte elastase inhibitor (SERPINB1).	[17]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Leukocyte elastase inhibitor (SERPINB1).	[18]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Leukocyte elastase inhibitor (SERPINB1).	[19]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Leukocyte elastase inhibitor (SERPINB1).	[20]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Leukocyte elastase inhibitor (SERPINB1).	[21]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Leukocyte elastase inhibitor (SERPINB1).	[22]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Leukocyte elastase inhibitor (SERPINB1).	[23]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Leukocyte elastase inhibitor (SERPINB1).	[24]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Leukocyte elastase inhibitor (SERPINB1).	[25]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Leukocyte elastase inhibitor (SERPINB1).	[26]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Leukocyte elastase inhibitor (SERPINB1).	[27]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Leukocyte elastase inhibitor (SERPINB1).	[25]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Leukocyte elastase inhibitor (SERPINB1).	[28]
Sulindac	DM2QHZU	Approved	Sulindac increases the expression of Leukocyte elastase inhibitor (SERPINB1).	[29]
Etretinate	DM2CZFA	Approved	Etretinate increases the expression of Leukocyte elastase inhibitor (SERPINB1).	[30]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Leukocyte elastase inhibitor (SERPINB1).	[19]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol increases the expression of Leukocyte elastase inhibitor (SERPINB1).	[31]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Leukocyte elastase inhibitor (SERPINB1).	[32]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Leukocyte elastase inhibitor (SERPINB1).	[33]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Leukocyte elastase inhibitor (SERPINB1).	[34]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Leukocyte elastase inhibitor (SERPINB1).	[36]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Leukocyte elastase inhibitor (SERPINB1).	[37]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride decreases the expression of Leukocyte elastase inhibitor (SERPINB1).	[38]
Flavone	DMEQH6J	Investigative	Flavone increases the expression of Leukocyte elastase inhibitor (SERPINB1).	[39]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Leukocyte elastase inhibitor (SERPINB1).	[35]

References

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