Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3Y8011)

• DOT Name: Cathelicidin antimicrobial peptide (CAMP)
• Synonyms: 18 kDa cationic antimicrobial protein; CAP-18; hCAP-18
• Gene Name: CAMP
• UniProt ID: CAMP_HUMAN
• PDB ID: 2FBS; 2FBU; 2FCG; 2K6O; 2LMF; 2NA3; 4EYC; 5NMN; 5NNK; 5NNM; 5NNT; 5XNG; 5XRX; 6BIV; 6BIX; 6S6M; 7NPQ; 7PDC; 7SAY; 8DEW
• Pfam ID: PF12153 ; PF00666
• Sequence:
  MKTQRDGHSLGRWSLVLLLLGLVMPLAIIAQVLSYKEAVLRAIDGINQRSSDANLYRLLD
  LDPRPTMDGDPDTPKPVSFTVKETVCPRTTQQSPEDCDFKKDGLVKRCMGTVTLNQARGS
  FDISCDKDNKRFALLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES
• Function: Antimicrobial protein that is an integral component of the innate immune system. Binds to bacterial lipopolysaccharides (LPS). Acts via neutrophil N-formyl peptide receptors to enhance the release of CXCL2. Postsecretory processing generates multiple cathelicidin antimicrobial peptides with various lengths which act as a topical antimicrobial defense in sweat on skin. The unprocessed precursor form, cathelicidin antimicrobial peptide, inhibits the growth of Gram-negative E.coli and E.aerogenes with efficiencies comparable to that of the mature peptide LL-37 (in vitro) ; [Antibacterial peptide LL-37]: Antimicrobial peptide that is an integral component of the innate immune system. Binds to bacterial lipopolysaccharides (LPS). Causes membrane permeabilization by forming transmembrane pores (in vitro). Causes lysis of E.coli. Exhibits antimicrobial activity against Gram-negative bacteria such as P.aeruginosa, S.typhimurium, E.aerogenes, E.coli and P.syringae, Gram-positive bacteria such as L.monocytogenes, S.epidermidis, S.pyogenes and S.aureus, as well as vancomycin-resistant enterococci (in vitro). Exhibits antimicrobial activity against methicillin-resistant S.aureus, P.mirabilis, and C.albicans in low-salt media, but not in media containing 100 mM NaCl (in vitro). Forms chiral supramolecular assemblies with quinolone signal (PQS) molecules of P.aeruginosa, which may lead to interference of bacterial quorum signaling and perturbance of bacterial biofilm formation. May form supramolecular fiber-like assemblies on bacterial membranes. Induces cytokine and chemokine production as well as TNF/TNFA and CSF2/GMCSF production in normal human keratinocytes. Exhibits hemolytic activity against red blood cells ; [Antibacterial peptide FALL-39]: Exhibits antimicrobial activity against E.coli and B.megaterium (in vitro); [Antibacterial peptide KR-20]: Acts synergistically with peptides KS-30 and KR-31, killing bacteria such as S.aureus, E.coli and C.albicans at lower concentrations when present together, and maintains activity at increased salt condition. Does not have the ability to stimulate CXCL8/IL8 release from keratinocytes ; [Antibacterial peptide LL-23]: Poorly active (MIC > 150 uM) against E.coli strain K12. Is able to induce the pro-inflammatory cytokine TNF/TNFA or the chemokine CCL2/MCP1 ; [Antibacterial peptide LL-29]: Moderately antibacterial; [Antibacterial peptide KS-30]: Moderately antibacterial. Acts synergistically with peptides KR-20 and KR-31, killing bacteria such as S.aureus, E.coli and C.albicans at lower concentrations when present together, and maintain activity at increased salt condition. Does not have the ability to stimulate CXCL8/IL8 release from keratinocytes ; [Antibacterial peptide RK-31]: Acts synergistically with peptides KS-30 and KR-31, killing bacteria such as S.aureus, E.coli and C.albicans at lower concentrations when present together, and maintain activity at increased salt condition. Does not have the ability to stimulate CXCL8/IL8 release from keratinocytes ; [Antibacterial peptide FF-33]: Inhibits the growth of E.coli and B.megaterium and exhibits hemolytic activity against human red blood cells.
• Tissue Specificity: Expressed in neutrophilic granulocytes (at protein level) . Expressed in bone marrow .; [Antibacterial peptide LL-37]: Expressed in granulocytes (at protein level) . Expressed by the eccrine apparatus and secreted into sweat on skin (at protein level) .; [Antibacterial peptide FALL-39]: Expressed in bone marrow and testis.
• KEGG Pathway:
  Neutrophil extracellular trap formation (hsa04613)
  NOD-like receptor sig.ling pathway (hsa04621)
  Salivary secretion (hsa04970)
  Staphylococcus aureus infection (hsa05150)
  Tuberculosis (hsa05152)
• Reactome Pathway:
  Antimicrobial peptides (R-HSA-6803157)
  Neutrophil degranulation (R-HSA-6798695)
• BioCyc Pathway: MetaCyc:ENSG00000164047-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Cathelicidin antimicrobial peptide (CAMP).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Cathelicidin antimicrobial peptide (CAMP).	[5]

15 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 Cathelicidin antimicrobial peptide (CAMP).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cathelicidin antimicrobial peptide (CAMP).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Cathelicidin antimicrobial peptide (CAMP).	[4]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Cathelicidin antimicrobial peptide (CAMP).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Cathelicidin antimicrobial peptide (CAMP).	[7]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Cathelicidin antimicrobial peptide (CAMP).	[8]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Cathelicidin antimicrobial peptide (CAMP).	[9]
Mifepristone	DMGZQEF	Approved	Mifepristone decreases the expression of Cathelicidin antimicrobial peptide (CAMP).	[8]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Cathelicidin antimicrobial peptide (CAMP).	[10]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol increases the expression of Cathelicidin antimicrobial peptide (CAMP).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Cathelicidin antimicrobial peptide (CAMP).	[11]
Lexacalcitol	DMJ3ZT8	Discontinued in Phase 2	Lexacalcitol increases the expression of Cathelicidin antimicrobial peptide (CAMP).	[7]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Cathelicidin antimicrobial peptide (CAMP).	[12]
(E)-4-(3,5-dimethoxystyryl)phenol	DMYXI2V	Investigative	(E)-4-(3,5-dimethoxystyryl)phenol increases the expression of Cathelicidin antimicrobial peptide (CAMP).	[10]
	DM9CEI5		increases the expression of Cathelicidin antimicrobial peptide (CAMP).	[13]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [3] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [4] Dual anti-inflammatory and anti-parasitic action of topical ivermectin 1% in papulopustular rosacea. J Eur Acad Dermatol Venereol. 2017 Nov;31(11):1907-1911. doi: 10.1111/jdv.14437. Epub 2017 Aug 29.
• [5] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [6] Global effects of inorganic arsenic on gene expression profile in human macrophages. Mol Immunol. 2009 Feb;46(4):649-56.
• [7] Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3. FASEB J. 2005 Jul;19(9):1067-77. doi: 10.1096/fj.04-3284com.
• [8] Expression and modulation of progesterone induced blocking factor (PIBF) and innate immune factors in human leukemia cell lines by progesterone and mifepristone. Leuk Lymphoma. 2007 Aug;48(8):1610-7. doi: 10.1080/10428190701471999.
• [9] Characterizing the genetic basis for nicotine induced cancer development: a transcriptome sequencing study. PLoS One. 2013 Jun 18;8(6):e67252.
• [10] Synergistic induction of human cathelicidin antimicrobial peptide gene expression by vitamin D and stilbenoids. Mol Nutr Food Res. 2014 Mar;58(3):528-536. doi: 10.1002/mnfr.201300266. Epub 2013 Sep 14.
• [11] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [12] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [13] Lithocholic acid derivatives act as selective vitamin D receptor modulators without inducing hypercalcemia. J Lipid Res. 2008 Apr;49(4):763-72. doi: 10.1194/jlr.M700293-JLR200. Epub 2008 Jan 7.