Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTK5YO7J)

• DOT Name: Programmed cell death protein 7 (PDCD7)
• Synonyms: ES18; hES18
• Gene Name: PDCD7
• Related Disease:
  Acute myelogenous leukaemia
  Oral cancer
  Oral cavity carcinoma
  Squamous cell carcinoma
• UniProt ID: PDCD7_HUMAN
• Pfam ID: PF16021
• Sequence:
  MALPPFFGQGRPGPPPPQPPPPAPFGCPPPPLPSPAFPPPLPQRPGPFPGASAPFLQPPL
  ALQPRASAEASRGGGGAGAFYPVPPPPLPPPPPQCRPFPGTDAGERPRPPPPGPGPPWSP
  RWPEAPPPPADVLGDAALQRLRDRQWLEAVFGTPRRAGCPVPQRTHAGPSLGEVRARLLR
  ALRLVRRLRGLSQALREAEADGAAWVLLYSQTAPLRAELAERLQPLTQAAYVGEARRRLE
  RVRRRRLRLRERAREREAEREAEAARAVEREQEIDRWRVKCVQEVEEKKREQELKAAADG
  VLSEVRKKQADTKRMVDILRALEKLRKLRKEAAARKGVCPPASADETFTHHLQRLRKLIK
  KRSELYEAEERALRVMLEGEQEEERKRELEKKQRKEKEKILLQKREIESKLFGDPDEFPL
  AHLLEPFRQYYLQAEHSLPALIQIRHDWDQYLVPSDHPKGNFVPQGWVLPPLPSNDIWAT
  AVKLH
• Function: Promotes apoptosis when overexpressed.
• Reactome Pathway: mRNA Splicing - Minor Pathway (R-HSA-72165)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Altered Expression	[1]
Oral cancer	DISLD42D	Strong	Altered Expression	[2]
Oral cavity carcinoma	DISZXMVL	Strong	Altered Expression	[2]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[2]

10 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 Programmed cell death protein 7 (PDCD7).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Programmed cell death protein 7 (PDCD7).	[4]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Programmed cell death protein 7 (PDCD7).	[5]
Cocaine	DMSOX7I	Approved	Cocaine increases the expression of Programmed cell death protein 7 (PDCD7).	[6]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Programmed cell death protein 7 (PDCD7).	[7]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Programmed cell death protein 7 (PDCD7).	[7]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Programmed cell death protein 7 (PDCD7).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Programmed cell death protein 7 (PDCD7).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Programmed cell death protein 7 (PDCD7).	[7]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Programmed cell death protein 7 (PDCD7).	[12]

2 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 affects the methylation of Programmed cell death protein 7 (PDCD7).	[8]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Programmed cell death protein 7 (PDCD7).	[10]

References

• [1] The clinical and prognostic significance of FIS1, SPI1, PDCD7 and Ang2 expression levels in acute myeloid leukemia.Cancer Genet. 2019 Apr;233-234:84-95. doi: 10.1016/j.cancergen.2018.12.001. Epub 2018 Dec 7.
• [2] miR-134 targets PDCD7 to reduce E-cadherin expression and enhance oral cancer progression.Int J Cancer. 2018 Dec 1;143(11):2892-2904. doi: 10.1002/ijc.31638. Epub 2018 Oct 4.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [6] Gene expression in human hippocampus from cocaine abusers identifies genes which regulate extracellular matrix remodeling. PLoS One. 2007 Nov 14;2(11):e1187. doi: 10.1371/journal.pone.0001187.
• [7] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [8] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [9] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [10] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [11] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [12] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.