Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPIL8IE)

• DOT Name: Carboxypeptidase B2 (CPB2)
• Synonyms: EC 3.4.17.20; Carboxypeptidase U; CPU; Plasma carboxypeptidase B; pCPB; Thrombin-activable fibrinolysis inhibitor; TAFI
• Gene Name: CPB2
• UniProt ID: CBPB2_HUMAN
• PDB ID: 3D66; 3D67; 3D68; 3LMS; 4P10; 5HVF; 5HVG; 5HVH; 7NEE; 7NEU
• EC Number: 3.4.17.20
• Pfam ID: PF00246 ; PF02244
• Sequence:
  MKLCSLAVLVPIVLFCEQHVFAFQSGQVLAALPRTSRQVQVLQNLTTTYEIVLWQPVTAD
  LIVKKKQVHFFVNASDVDNVKAHLNVSGIPCSVLLADVEDLIQQQISNDTVSPRASASYY
  EQYHSLNEIYSWIEFITERHPDMLTKIHIGSSFEKYPLYVLKVSGKEQAAKNAIWIDCGI
  HAREWISPAFCLWFIGHITQFYGIIGQYTNLLRLVDFYVMPVVNVDGYDYSWKKNRMWRK
  NRSFYANNHCIGTDLNRNFASKHWCEEGASSSSCSETYCGLYPESEPEVKAVASFLRRNI
  NQIKAYISMHSYSQHIVFPYSYTRSKSKDHEELSLVASEAVRAIEKISKNTRYTHGHGSE
  TLYLAPGGGDDWIYDLGIKYSFTIELRDTGTYGFLLPERYIKPTCREAFAAVSKIAWHVI
  RNV
• Function: Cleaves C-terminal arginine or lysine residues from biologically active peptides such as kinins or anaphylatoxins in the circulation thereby regulating their activities. Down-regulates fibrinolysis by removing C-terminal lysine residues from fibrin that has already been partially degraded by plasmin.
• Tissue Specificity: Plasma; synthesized in the liver.
• KEGG Pathway:
  Complement and coagulation cascades (hsa04610)
  Pancreatic secretion (hsa04972)
  Protein digestion and absorption (hsa04974)
• Reactome Pathway:
  Regulation of Complement cascade (R-HSA-977606)
  Metabolism of Angiotensinogen to Angiotensins (R-HSA-2022377)

Molecular Interaction Atlas (MIA) of This DOT

14 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 Carboxypeptidase B2 (CPB2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Carboxypeptidase B2 (CPB2).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Carboxypeptidase B2 (CPB2).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Carboxypeptidase B2 (CPB2).	[4]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Carboxypeptidase B2 (CPB2).	[5]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Carboxypeptidase B2 (CPB2).	[6]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Carboxypeptidase B2 (CPB2).	[7]
Orlistat	DMRJSP8	Approved	Orlistat decreases the expression of Carboxypeptidase B2 (CPB2).	[8]
Epanova	DMHEAGL	Approved	Epanova decreases the expression of Carboxypeptidase B2 (CPB2).	[9]
Desogestrel	DM27U4Y	Approved	Desogestrel increases the activity of Carboxypeptidase B2 (CPB2).	[10]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 decreases the expression of Carboxypeptidase B2 (CPB2).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Carboxypeptidase B2 (CPB2).	[11]
Mivebresib	DMCPF90	Phase 1	Mivebresib decreases the expression of Carboxypeptidase B2 (CPB2).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Carboxypeptidase B2 (CPB2).	[13]

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 Carboxypeptidase B2 (CPB2).	[12]

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] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [6] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [7] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [8] Decrements in the thrombin activatable fibrinolysis inhibitor (TAFI) levels in association with orlistat treatment in obesity. Clin Appl Thromb Hemost. 2006 Jul;12(3):364-8. doi: 10.1177/1076029606291403.
• [9] Differential effects of omega-3 and omega-6 Fatty acids on gene expression in breast cancer cells. Breast Cancer Res Treat. 2007 Jan;101(1):7-16. doi: 10.1007/s10549-006-9269-x. Epub 2006 Jul 6.
• [10] Oral contraceptives, thrombosis and haemostasis. Eur J Obstet Gynecol Reprod Biol. 2001 Apr;95(2):193-7. doi: 10.1016/s0301-2115(00)00489-9.
• [11] Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells. PLoS One. 2022 Apr 29;17(4):e0266966. doi: 10.1371/journal.pone.0266966. eCollection 2022.
• [12] 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.
• [13] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.