Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUNFUU8)

• DOT Name: Antileukoproteinase (SLPI)
• Synonyms: ALP; BLPI; HUSI-1; Mucus proteinase inhibitor; MPI; Protease inhibitor WAP4; Secretory leukocyte protease inhibitor; Seminal proteinase inhibitor; WAP four-disulfide core domain protein 4
• Gene Name: SLPI
• Related Disease:
  Adenocarcinoma
  Advanced cancer
  Cardiac failure
  Chronic obstructive pulmonary disease
  Clear cell renal carcinoma
  Colon cancer
  Colon carcinoma
  Congestive heart failure
  Endophthalmitis
  Epithelial ovarian cancer
  Hepatocellular carcinoma
  Herpes simplex infection
  High blood pressure
  Lung cancer
  Lymphoma
  Neoplasm
  Non-small-cell lung cancer
  Oral cancer
  Osteoarthritis
  Ovarian neoplasm
  Prostate cancer
  Prostate carcinoma
  Pyropoikilocytosis, hereditary
  Renal cell carcinoma
  Rheumatoid arthritis
  Squamous cell carcinoma
  Telangiectasia, hereditary hemorrhagic, type 2
  Ulcerative colitis
  Adult lymphoma
  Alzheimer disease
  Gastric cancer
  Hepatitis C virus infection
  Lung carcinoma
  Nasopharyngeal carcinoma
  Ovarian cancer
  Pediatric lymphoma
  Stomach cancer
  Head-neck squamous cell carcinoma
  Hereditary hemorrhagic telangiectasia
  Human papillomavirus infection
  Hypophosphatasia
  Myocardial infarction
  Osteoporosis
  Polycystic ovarian syndrome
• UniProt ID: SLPI_HUMAN
• PDB ID: 2Z7F; 4DOQ
• Pfam ID: PF00095
• Sequence:
  MKSSGLFPFLVLLALGTLAPWAVEGSGKSFKAGVCPPKKSAQCLRYKKPECQSDWQCPGK
  KRCCPDTCGIKCLDPVDTPNPTRRKPGKCPVTYGQCLMLNPPNFCEMDGQCKRDLKCCMG
  MCGKSCVSPVKA
• Function: Acid-stable proteinase inhibitor with strong affinities for trypsin, chymotrypsin, elastase, and cathepsin G. Modulates the inflammatory and immune responses after bacterial infection, and after infection by the intracellular parasite L.major. Down-regulates responses to bacterial lipopolysaccharide (LPS). Plays a role in regulating the activation of NF-kappa-B and inflammatory responses. Has antimicrobial activity against mycobacteria, but not against salmonella. Contributes to normal resistance against infection by M.tuberculosis. Required for normal resistance to infection by L.major. Required for normal wound healing, probably by preventing tissue damage by limiting protease activity. Together with ELANE, required for normal differentiation and proliferation of bone marrow myeloid cells.
• Tissue Specificity: Detected in blood plasma . Detected in bone marrow myeloid cells . Detected in airway sputum . Detected in parotid gland secretions . Detected in seminal plasma (at protein level) . Detected in uterus cervix .
• Reactome Pathway: Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

44 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Definitive	Genetic Variation	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Cardiac failure	DISDC067	Strong	Altered Expression	[3]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Altered Expression	[4]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[5]
Colon cancer	DISVC52G	Strong	Altered Expression	[6]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[6]
Congestive heart failure	DIS32MEA	Strong	Altered Expression	[3]
Endophthalmitis	DISCQV4J	Strong	Biomarker	[7]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[8]
Hepatocellular carcinoma	DIS0J828	Strong	Genetic Variation	[9]
Herpes simplex infection	DISL1SAV	Strong	Biomarker	[10]
High blood pressure	DISY2OHH	Strong	Biomarker	[11]
Lung cancer	DISCM4YA	Strong	Biomarker	[12]
Lymphoma	DISN6V4S	Strong	Biomarker	[13]
Neoplasm	DISZKGEW	Strong	Biomarker	[14]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[15]
Oral cancer	DISLD42D	Strong	Altered Expression	[16]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[17]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[8]
Prostate cancer	DISF190Y	Strong	Biomarker	[18]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[18]
Pyropoikilocytosis, hereditary	DISZGN3B	Strong	Biomarker	[19]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[5]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[20]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[21]
Telangiectasia, hereditary hemorrhagic, type 2	DISOYV2U	Strong	Genetic Variation	[22]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[23]
Adult lymphoma	DISK8IZR	moderate	Biomarker	[13]
Alzheimer disease	DISF8S70	moderate	Biomarker	[24]
Gastric cancer	DISXGOUK	moderate	Biomarker	[25]
Hepatitis C virus infection	DISQ0M8R	moderate	Genetic Variation	[26]
Lung carcinoma	DISTR26C	moderate	Biomarker	[12]
Nasopharyngeal carcinoma	DISAOTQ0	moderate	Altered Expression	[27]
Ovarian cancer	DISZJHAP	moderate	Altered Expression	[25]
Pediatric lymphoma	DIS51BK2	moderate	Biomarker	[13]
Stomach cancer	DISKIJSX	moderate	Biomarker	[25]
Head-neck squamous cell carcinoma	DISF7P24	Limited	Altered Expression	[28]
Hereditary hemorrhagic telangiectasia	DISXTDNT	Limited	Biomarker	[29]
Human papillomavirus infection	DISX61LX	Limited	Altered Expression	[28]
Hypophosphatasia	DISCQ0O2	Limited	Biomarker	[30]
Myocardial infarction	DIS655KI	Limited	Therapeutic	[31]
Osteoporosis	DISF2JE0	Limited	Altered Expression	[32]
Polycystic ovarian syndrome	DISZ2BNG	Limited	Biomarker	[33]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	Antileukoproteinase (SLPI) affects the response to substance of Temozolomide.	[48]
DTI-015	DMXZRW0	Approved	Antileukoproteinase (SLPI) affects the response to substance of DTI-015.	[48]

1 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 Antileukoproteinase (SLPI).	[34]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Antileukoproteinase (SLPI).	[35]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Antileukoproteinase (SLPI).	[36]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Antileukoproteinase (SLPI).	[37]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Antileukoproteinase (SLPI).	[38]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Antileukoproteinase (SLPI).	[39]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Antileukoproteinase (SLPI).	[40]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Antileukoproteinase (SLPI).	[41]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Antileukoproteinase (SLPI).	[42]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Antileukoproteinase (SLPI).	[43]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Antileukoproteinase (SLPI).	[44]
Diclofenac	DMPIHLS	Approved	Diclofenac increases the expression of Antileukoproteinase (SLPI).	[43]
Benzatropine	DMF7EXL	Approved	Benzatropine increases the expression of Antileukoproteinase (SLPI).	[43]
Liothyronine	DM6IR3P	Approved	Liothyronine increases the expression of Antileukoproteinase (SLPI).	[43]
Rofecoxib	DM3P5DA	Approved	Rofecoxib increases the expression of Antileukoproteinase (SLPI).	[43]
Nefazodone	DM4ZS8M	Approved	Nefazodone increases the expression of Antileukoproteinase (SLPI).	[43]
Isoproterenol	DMK7MEY	Approved	Isoproterenol increases the expression of Antileukoproteinase (SLPI).	[43]
Isoniazid	DM5JVS3	Approved	Isoniazid increases the expression of Antileukoproteinase (SLPI).	[43]
Ximelegatran	DMU8ANS	Approved	Ximelegatran decreases the expression of Antileukoproteinase (SLPI).	[45]
Mebendazole	DMO14SG	Approved	Mebendazole increases the expression of Antileukoproteinase (SLPI).	[43]
Clavulanate	DM2FGRT	Approved	Clavulanate increases the expression of Antileukoproteinase (SLPI).	[43]
Flutamide	DMK0O7U	Approved	Flutamide increases the expression of Antileukoproteinase (SLPI).	[43]
Etodolac	DM6WJO9	Approved	Etodolac increases the expression of Antileukoproteinase (SLPI).	[43]
Loratadine	DMF3AN7	Approved	Loratadine increases the expression of Antileukoproteinase (SLPI).	[43]
Salbutamol	DMN9CWF	Approved	Salbutamol decreases the expression of Antileukoproteinase (SLPI).	[43]
Tolcapone	DM8MNVO	Approved	Tolcapone decreases the expression of Antileukoproteinase (SLPI).	[43]
Zafirlukast	DMHNQOG	Approved	Zafirlukast increases the expression of Antileukoproteinase (SLPI).	[43]
Fexofenadine	DM17ONX	Approved	Fexofenadine increases the expression of Antileukoproteinase (SLPI).	[43]
Entacapone	DMLBVKQ	Approved	Entacapone decreases the expression of Antileukoproteinase (SLPI).	[43]
Trazodone	DMK1GBJ	Approved	Trazodone increases the expression of Antileukoproteinase (SLPI).	[43]
Primaquine	DMWQ16I	Approved	Primaquine increases the expression of Antileukoproteinase (SLPI).	[43]
Atropine	DMEN6X7	Approved	Atropine increases the expression of Antileukoproteinase (SLPI).	[43]
Bromfenac	DMKB79O	Approved	Bromfenac increases the expression of Antileukoproteinase (SLPI).	[43]
Ethambutol	DMR87LC	Approved	Ethambutol increases the expression of Antileukoproteinase (SLPI).	[43]
Fluticasone propionate	DMRWLB2	Approved	Fluticasone propionate increases the expression of Antileukoproteinase (SLPI).	[46]
Fludrocortisone	DMUDIR8	Approved	Fludrocortisone increases the expression of Antileukoproteinase (SLPI).	[43]
Amikacin	DM5PDRB	Approved	Amikacin increases the expression of Antileukoproteinase (SLPI).	[43]
Lumiracoxib	DM1S4AG	Approved	Lumiracoxib decreases the expression of Antileukoproteinase (SLPI).	[43]
Trihexyphenidyl	DMB19L8	Approved	Trihexyphenidyl increases the expression of Antileukoproteinase (SLPI).	[43]
Procyclidine	DMHFJDT	Approved	Procyclidine increases the expression of Antileukoproteinase (SLPI).	[43]
Penbutolol	DM4ES8F	Approved	Penbutolol increases the expression of Antileukoproteinase (SLPI).	[43]
Aciclovir	DMYLOVR	Approved	Aciclovir increases the expression of Antileukoproteinase (SLPI).	[43]
Primidone	DM0WX6I	Approved	Primidone decreases the expression of Antileukoproteinase (SLPI).	[43]
Levofloxacin	DMS60RB	Approved	Levofloxacin decreases the expression of Antileukoproteinase (SLPI).	[43]
Didanosine	DMI2QPE	Approved	Didanosine increases the expression of Antileukoproteinase (SLPI).	[43]
Diphenhydramine	DMKQTBA	Approved	Diphenhydramine increases the expression of Antileukoproteinase (SLPI).	[43]
Aminosalicylic acid	DMENSL5	Approved	Aminosalicylic acid increases the expression of Antileukoproteinase (SLPI).	[43]
Pirprofen	DMMOFHT	Approved	Pirprofen increases the expression of Antileukoproteinase (SLPI).	[43]
Protriptyline	DMNHTZI	Approved	Protriptyline increases the expression of Antileukoproteinase (SLPI).	[43]
Hydroxyzine	DMF8Y74	Approved	Hydroxyzine increases the expression of Antileukoproteinase (SLPI).	[43]
Minoxidil	DMA2Z4F	Approved	Minoxidil increases the expression of Antileukoproteinase (SLPI).	[43]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Antileukoproteinase (SLPI).	[47]
Ticrynafen	DMLFSTR	Withdrawn from market	Ticrynafen increases the expression of Antileukoproteinase (SLPI).	[43]
Nomifensine	DMCP2TS	Withdrawn from market	Nomifensine increases the expression of Antileukoproteinase (SLPI).	[43]
Nimesulide	DMR1NMD	Terminated	Nimesulide increases the expression of Antileukoproteinase (SLPI).	[43]
IPRONIAZIDE	DM42ENF	Investigative	IPRONIAZIDE increases the expression of Antileukoproteinase (SLPI).	[43]
Oxybutynine	DMJPBAX	Investigative	Oxybutynine increases the expression of Antileukoproteinase (SLPI).	[43]

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