Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNN9LJ5)

• DOT Name: Bactericidal permeability-increasing protein (BPI)
• Synonyms: BPI; CAP 57
• Gene Name: BPI
• UniProt ID: BPI_HUMAN
• PDB ID: 1BP1; 1EWF
• Pfam ID: PF01273 ; PF02886
• Sequence:
  MRENMARGPCNAPRWASLMVLVAIGTAVTAAVNPGVVVRISQKGLDYASQQGTAALQKEL
  KRIKIPDYSDSFKIKHLGKGHYSFYSMDIREFQLPSSQISMVPNVGLKFSISNANIKISG
  KWKAQKRFLKMSGNFDLSIEGMSISADLKLGSNPTSGKPTITCSSCSSHINSVHVHISKS
  KVGWLIQLFHKKIESALRNKMNSQVCEKVTNSVSSELQPYFQTLPVMTKIDSVAGINYGL
  VAPPATTAETLDVQMKGEFYSENHHNPPPFAPPVMEFPAAHDRMVYLGLSDYFFNTAGLV
  YQEAGVLKMTLRDDMIPKESKFRLTTKFFGTFLPEVAKKFPNMKIQIHVSASTPPHLSVQ
  PTGLTFYPAVDVQAFAVLPNSSLASLFLIGMHTTGSMEVSAESNRLVGELKLDRLLLELK
  HSNIGPFPVELLQDIMNYIVPILVLPRVNEKLQKGFPLPTPARVQLYNVVLQPHQNFLLF
  GADVVYK
• Function: The cytotoxic action of BPI is limited to many species of Gram-negative bacteria; this specificity may be explained by a strong affinity of the very basic N-terminal half for the negatively charged lipopolysaccharides that are unique to the Gram-negative bacterial outer envelope. Has antibacterial activity against the Gram-negative bacterium P.aeruginosa, this activity is inhibited by LPS from P.aeruginosa.
• Tissue Specificity: Restricted to cells of the myeloid series.
• Reactome Pathway:
  Neutrophil degranulation (R-HSA-6798695)
  Antimicrobial peptides (R-HSA-6803157)
  Toll Like Receptor 4 (TLR4) Cascade (R-HSA-166016)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Bactericidal permeability-increasing protein (BPI).	[1]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Bactericidal permeability-increasing protein (BPI).	[2]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide decreases the expression of Bactericidal permeability-increasing protein (BPI).	[3]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Bactericidal permeability-increasing protein (BPI).	[1]

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 Bactericidal permeability-increasing protein (BPI).	[4]

References

• [1] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [2] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [3] Comparative gene expression analysis of a chronic myelogenous leukemia cell line resistant to cyclophosphamide using oligonucleotide arrays and response to tyrosine kinase inhibitors. Leuk Res. 2007 Nov;31(11):1511-20.
• [4] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.