Details of Drug Off-Target (DOT)

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

• DOT Name: Inactive carboxypeptidase-like protein X2 (CPXM2)
• Gene Name: CPXM2
• Related Disease:
  Bone osteosarcoma
  Osteosarcoma
  Male infertility
  Neoplasm
  Fetal growth restriction
  Gastric cancer
  Gonorrhea
  Stomach cancer
• UniProt ID: CPXM2_HUMAN
• Pfam ID: PF13620 ; PF00754 ; PF00246
• Sequence:
  MSRPGTATPALALVLLAVTLAGVGAQGAALEDPDYYGQEIWSREPYYARPEPELETFSPP
  LPAGPGEEWERRPQEPRPPKRATKPKKAPKREKSAPEPPPPGKHSNKKVMRTKSSEKAAN
  DDHSVRVAREDVRESCPPLGLETLKITDFQLHASTVKRYGLGAHRGRLNIQAGINENDFY
  DGAWCAGRNDLQQWIEVDARRLTRFTGVITQGRNSLWLSDWVTSYKVMVSNDSHTWVTVK
  NGSGDMIFEGNSEKEIPVLNELPVPMVARYIRINPQSWFDNGSICMRMEILGCPLPDPNN
  YYHRRNEMTTTDDLDFKHHNYKEMRQLMKVVNEMCPNITRIYNIGKSHQGLKLYAVEISD
  HPGEHEVGEPEFHYIAGAHGNEVLGRELLLLLVQFVCQEYLARNARIVHLVEETRIHVLP
  SLNPDGYEKAYEGGSELGGWSLGRWTHDGIDINNNFPDLNTLLWEAEDRQNVPRKVPNHY
  IAIPEWFLSENATVAAETRAVIAWMEKIPFVLGGNLQGGELVVAYPYDLVRSPWKTQEHT
  PTPDDHVFRWLAYSYASTHRLMTDARRRVCHTEDFQKEEGTVNGASWHTVAGSLNDFSYL
  HTNCFELSIYVGCDKYPHESQLPEEWENNRESLIVFMEQVHRGIKGLVRDSHGKGIPNAI
  ISVEGINHDIRTANDGDYWRLLNPGEYVVTAKAEGFTASTKNCMVGYDMGATRCDFTLSK
  TNMARIREIMEKFGKQPVSLPARRLKLRGQKRRQRG
• Function: May be involved in cell-cell interactions.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bone osteosarcoma	DIST1004	Definitive	Altered Expression	[1]
Osteosarcoma	DISLQ7E2	Definitive	Altered Expression	[1]
Male infertility	DISY3YZZ	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Fetal growth restriction	DIS5WEJ5	moderate	Altered Expression	[3]
Gastric cancer	DISXGOUK	Limited	Biomarker	[4]
Gonorrhea	DISQ5AO6	Limited	Biomarker	[4]
Stomach cancer	DISKIJSX	Limited	Biomarker	[4]

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 Inactive carboxypeptidase-like protein X2 (CPXM2).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Inactive carboxypeptidase-like protein X2 (CPXM2).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Inactive carboxypeptidase-like protein X2 (CPXM2).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Inactive carboxypeptidase-like protein X2 (CPXM2).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Inactive carboxypeptidase-like protein X2 (CPXM2).	[8]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Inactive carboxypeptidase-like protein X2 (CPXM2).	[9]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Inactive carboxypeptidase-like protein X2 (CPXM2).	[10]
Permethrin	DMZ0Q1G	Approved	Permethrin decreases the expression of Inactive carboxypeptidase-like protein X2 (CPXM2).	[11]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Inactive carboxypeptidase-like protein X2 (CPXM2).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Inactive carboxypeptidase-like protein X2 (CPXM2).	[13]

References

• [1] Overexpression of carboxypeptidase X M14 family member 2 predicts an unfavorable prognosis and promotes proliferation and migration of osteosarcoma.Diagn Pathol. 2019 Oct 24;14(1):118. doi: 10.1186/s13000-019-0887-0.
• [2] Role of Cytosolic Carboxypeptidase 5 in Neuronal Survival and Spermatogenesis.Sci Rep. 2017 Jan 27;7:41428. doi: 10.1038/srep41428.
• [3] Differential placental gene expression in term pregnancies affected by fetal growth restriction and macrosomia.Fetal Diagn Ther. 2014;36(2):173-80. doi: 10.1159/000360535. Epub 2014 Mar 28.
• [4] Overexpression of CPXM2 predicts an unfavorable prognosis and promotes the proliferation and migration of gastric cancer.Oncol Rep. 2019 Oct;42(4):1283-1294. doi: 10.3892/or.2019.7254. Epub 2019 Jul 30.
• [5] 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.
• [6] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [7] Epidermal growth factor receptor signalling in human breast cancer cells operates parallel to estrogen receptor alpha signalling and results in tamoxifen insensitive proliferation. BMC Cancer. 2014 Apr 23;14:283.
• [8] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [9] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [10] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [11] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [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] 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.