Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSI8BE6)

• DOT Name: Carboxypeptidase M (CPM)
• Synonyms: CPM; EC 3.4.17.12
• Gene Name: CPM
• UniProt ID: CBPM_HUMAN
• PDB ID: 1UWY
• EC Number: 3.4.17.12
• Pfam ID: PF13620 ; PF00246
• Sequence:
  MDFPCLWLGLLLPLVAALDFNYHRQEGMEAFLKTVAQNYSSVTHLHSIGKSVKGRNLWVL
  VVGRFPKEHRIGIPEFKYVANMHGDETVGRELLLHLIDYLVTSDGKDPEITNLINSTRIH
  IMPSMNPDGFEAVKKPDCYYSIGRENYNQYDLNRNFPDAFEYNNVSRQPETVAVMKWLKT
  ETFVLSANLHGGALVASYPFDNGVQATGALYSRSLTPDDDVFQYLAHTYASRNPNMKKGD
  ECKNKMNFPNGVTNGYSWYPLQGGMQDYNYIWAQCFEITLELSCCKYPREEKLPSFWNNN
  KASLIEYIKQVHLGVKGQVFDQNGNPLPNVIVEVQDRKHICPYRTNKYGEYYLLLLPGSY
  IINVTVPGHDPHITKVIIPEKSQNFSALKKDILLPFQGQLDSIPVSNPSCPMIPLYRNLP
  DHSAATKPSLFLFLVSLLHIFFK
• Function: Specifically removes C-terminal basic residues (Arg or Lys) from peptides and proteins. It is believed to play important roles in the control of peptide hormone and growth factor activity at the cell surface, and in the membrane-localized degradation of extracellular proteins.
• Reactome Pathway: Post-translational modification (R-HSA-163125)

Molecular Interaction Atlas (MIA) of This DOT

17 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 Carboxypeptidase M (CPM).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Carboxypeptidase M (CPM).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Carboxypeptidase M (CPM).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Carboxypeptidase M (CPM).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Carboxypeptidase M (CPM).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Carboxypeptidase M (CPM).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Carboxypeptidase M (CPM).	[7]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Carboxypeptidase M (CPM).	[8]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Carboxypeptidase M (CPM).	[9]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Carboxypeptidase M (CPM).	[10]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Carboxypeptidase M (CPM).	[11]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of Carboxypeptidase M (CPM).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Carboxypeptidase M (CPM).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Carboxypeptidase M (CPM).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Carboxypeptidase M (CPM).	[16]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Carboxypeptidase M (CPM).	[17]
Manganese	DMKT129	Investigative	Manganese decreases the expression of Carboxypeptidase M (CPM).	[18]

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 M (CPM).	[13]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] 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.
• [4] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [7] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [8] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [9] Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007 Apr;64(7-8):1009-32.
• [10] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [11] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [12] Gene expression preferentially regulated by tamoxifen in breast cancer cells and correlations with clinical outcome. Cancer Res. 2006 Jul 15;66(14):7334-40.
• [13] 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.
• [14] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [15] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [16] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [17] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [18] Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells. Neurotoxicology. 2007 May;28(3):478-89.