Details of Drug Off-Target (DOT)

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

• DOT Name: Plasma serine protease inhibitor (SERPINA5)
• Synonyms: Acrosomal serine protease inhibitor; Plasminogen activator inhibitor 3; PAI-3; PAI3; Protein C inhibitor; PCI; Serpin A5
• Gene Name: SERPINA5
• Related Disease:
  Non-insulin dependent diabetes
  Short chain acyl-CoA dehydrogenase deficiency
  Acute coronary syndrome
  Autism spectrum disorder
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Cardiac failure
  Classic Hodgkin lymphoma
  Clear cell renal carcinoma
  Congestive heart failure
  Depression
  Epithelial ovarian cancer
  Gastric cancer
  Hepatocellular carcinoma
  Neoplasm
  Neuroblastoma
  Obesity
  Ovarian cancer
  Ovarian neoplasm
  Prostate cancer
  Prostate carcinoma
  Renal cell carcinoma
  Sarcoma
  Schizophrenia
  Small lymphocytic lymphoma
  Small-cell lung cancer
  Stomach cancer
  Stroke
  Adult lymphoma
  High blood pressure
  Lymphoma
  Pediatric lymphoma
  Peripheral vascular disease
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid tumor
  Advanced cancer
  Cardiomyopathy
  Cardiovascular disease
  Cholestasis
  Erythema multiforme
  Head-neck squamous cell carcinoma
  Parkinson disease
  Plasma cell myeloma
  Thyroid gland papillary carcinoma
• UniProt ID: IPSP_HUMAN
• PDB ID: 1LQ8; 2HI9; 2OL2; 3DY0
• Pfam ID: PF00079
• Sequence:
  MQLFLLLCLVLLSPQGASLHRHHPREMKKRVEDLHVGATVAPSSRRDFTFDLYRALASAA
  PSQSIFFSPVSISMSLAMLSLGAGSSTKMQILEGLGLNLQKSSEKELHRGFQQLLQELNQ
  PRDGFQLSLGNALFTDLVVDLQDTFVSAMKTLYLADTFPTNFRDSAGAMKQINDYVAKQT
  KGKIVDLLKNLDSNAVVIMVNYIFFKAKWETSFNHKGTQEQDFYVTSETVVRVPMMSRED
  QYHYLLDRNLSCRVVGVPYQGNATALFILPSEGKMQQVENGLSEKTLRKWLKMFKKRQLE
  LYLPKFSIEGSYQLEKVLPSLGISNVFTSHADLSGISNHSNIQVSEMVHKAVVEVDESGT
  RAAAATGTIFTFRSARLNSQRLVFNRPFLMFIVDNNILFLGKVNRP
• Function: Heparin-dependent serine protease inhibitor acting in body fluids and secretions. Inactivates serine proteases by binding irreversibly to their serine activation site. Involved in the regulation of intravascular and extravascular proteolytic activities. Plays hemostatic roles in the blood plasma. Acts as a procoagulant and pro-inflammatory factor by inhibiting the anticoagulant activated protein C factor as well as the generation of activated protein C factor by the thrombin/thrombomodulin complex. Acts as an anticoagulant factor by inhibiting blood coagulation factors like prothrombin, factor XI, factor Xa, plasma kallikrein and fibrinolytic enzymes such as tissue- and urinary-type plasminogen activators. In seminal plasma, inactivates several serine proteases implicated in the reproductive system. Inhibits the serpin acrosin; indirectly protects component of the male genital tract from being degraded by excessive released acrosin. Inhibits tissue- and urinary-type plasminogen activator, prostate-specific antigen and kallikrein activities; has a control on the sperm motility and fertilization. Inhibits the activated protein C-catalyzed degradation of SEMG1 and SEMG2; regulates the degradation of semenogelin during the process of transfer of spermatozoa from the male reproductive tract into the female tract. In urine, inhibits urinary-type plasminogen activator and kallikrein activities. Inactivates membrane-anchored serine proteases activities such as MPRSS7 and TMPRSS11E. Inhibits urinary-type plasminogen activator-dependent tumor cell invasion and metastasis. May also play a non-inhibitory role in seminal plasma and urine as a hydrophobic hormone carrier by its binding to retinoic acid.
• Tissue Specificity: Predominantly expressed in the epithelium of seminal vesicles. Expressed in the proximal tubular epithelium of the kidney. Expressed in the superficial and more differentiated epidermal keratinocytes of the skin. Expressed in megakaryocytes and platelets. Expressed poorly in kidney tumor cells compared to non tumor kidney tissues. Expressed in spermatozoa. Present in very high concentration in seminal plasma. Present in high concentration in plasma, synovial and Graaf follicle fluids. Present in low concentration in breast milk and in amniotic fluids. Present in very low concentration in urine, cerebrospinal fluids, saliva and tears (at protein level). Strongly expressed in liver. Expressed in kidney, spleen, pancreas, skeletal muscle, heart, testes, ovary, interstitial Leydig cells, epididymal glands, seminal vesicles and prostate.
• KEGG Pathway: Complement and coagulation cascades (hsa04610)
• Reactome Pathway:
  Common Pathway of Fibrin Clot Formation (R-HSA-140875)
  Intrinsic Pathway of Fibrin Clot Formation (R-HSA-140837)

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Biomarker	[1]
Short chain acyl-CoA dehydrogenase deficiency	DISDDRPY	Definitive	Biomarker	[2]
Acute coronary syndrome	DIS7DYEW	Strong	Biomarker	[3]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[5]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[5]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[6]
Cardiac failure	DISDC067	Strong	Biomarker	[7]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Biomarker	[8]
Clear cell renal carcinoma	DISBXRFJ	Strong	Genetic Variation	[9]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[7]
Depression	DIS3XJ69	Strong	Biomarker	[10]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[11]
Gastric cancer	DISXGOUK	Strong	Biomarker	[12]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[13]
Neoplasm	DISZKGEW	Strong	Biomarker	[14]
Neuroblastoma	DISVZBI4	Strong	Genetic Variation	[15]
Obesity	DIS47Y1K	Strong	Biomarker	[16]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[11]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[11]
Prostate cancer	DISF190Y	Strong	Altered Expression	[17]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[17]
Renal cell carcinoma	DISQZ2X8	Strong	Genetic Variation	[9]
Sarcoma	DISZDG3U	Strong	Biomarker	[18]
Schizophrenia	DISSRV2N	Strong	Biomarker	[19]
Small lymphocytic lymphoma	DIS30POX	Strong	Biomarker	[20]
Small-cell lung cancer	DISK3LZD	Strong	Biomarker	[21]
Stomach cancer	DISKIJSX	Strong	Biomarker	[12]
Stroke	DISX6UHX	Strong	Biomarker	[2]
Adult lymphoma	DISK8IZR	moderate	Biomarker	[22]
High blood pressure	DISY2OHH	moderate	Genetic Variation	[23]
Lymphoma	DISN6V4S	moderate	Biomarker	[22]
Pediatric lymphoma	DIS51BK2	moderate	Biomarker	[22]
Peripheral vascular disease	DISXSU1Y	moderate	Biomarker	[24]
Thyroid cancer	DIS3VLDH	moderate	Biomarker	[25]
Thyroid gland carcinoma	DISMNGZ0	moderate	Biomarker	[25]
Thyroid tumor	DISLVKMD	moderate	Biomarker	[25]
Advanced cancer	DISAT1Z9	Limited	Genetic Variation	[26]
Cardiomyopathy	DISUPZRG	Limited	Biomarker	[27]
Cardiovascular disease	DIS2IQDX	Limited	Biomarker	[28]
Cholestasis	DISDJJWE	Limited	Biomarker	[29]
Erythema multiforme	DISKCLM1	Limited	Biomarker	[30]
Head-neck squamous cell carcinoma	DISF7P24	Limited	Biomarker	[31]
Parkinson disease	DISQVHKL	Limited	Biomarker	[32]
Plasma cell myeloma	DIS0DFZ0	Limited	Biomarker	[33]
Thyroid gland papillary carcinoma	DIS48YMM	Limited	Genetic Variation	[34]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Methamphetamine	DMPM4SK	Approved	Plasma serine protease inhibitor (SERPINA5) affects the response to substance of Methamphetamine.	[53]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Plasma serine protease inhibitor (SERPINA5).	[35]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Plasma serine protease inhibitor (SERPINA5).	[36]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Plasma serine protease inhibitor (SERPINA5).	[37]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Plasma serine protease inhibitor (SERPINA5).	[38]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Plasma serine protease inhibitor (SERPINA5).	[39]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Plasma serine protease inhibitor (SERPINA5).	[40]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Plasma serine protease inhibitor (SERPINA5).	[41]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Plasma serine protease inhibitor (SERPINA5).	[42]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Plasma serine protease inhibitor (SERPINA5).	[43]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Plasma serine protease inhibitor (SERPINA5).	[44]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Plasma serine protease inhibitor (SERPINA5).	[45]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Plasma serine protease inhibitor (SERPINA5).	[46]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Plasma serine protease inhibitor (SERPINA5).	[47]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of Plasma serine protease inhibitor (SERPINA5).	[48]
ARZOXIFENE	DMOKCVI	Approved	ARZOXIFENE increases the expression of Plasma serine protease inhibitor (SERPINA5).	[40]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Plasma serine protease inhibitor (SERPINA5).	[49]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Plasma serine protease inhibitor (SERPINA5).	[50]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Plasma serine protease inhibitor (SERPINA5).	[51]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Plasma serine protease inhibitor (SERPINA5).	[52]

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