Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKAGZY3)

• DOT Name: S-adenosylmethionine decarboxylase proenzyme (AMD1)
• Synonyms: AdoMetDC; SAMDC; EC 4.1.1.50
• Gene Name: AMD1
• UniProt ID: DCAM_HUMAN
• PDB ID: 1I72; 1I79; 1I7B; 1I7C; 1I7M; 1JEN; 1JL0; 1MSV; 3DZ2; 3DZ3; 3DZ4; 3DZ5; 3DZ6; 3DZ7; 3EP3; 3EP4; 3EP5; 3EP6; 3EP7; 3EP8; 3EP9; 3EPA; 3EPB; 3H0V; 3H0W
• EC Number: 4.1.1.50
• Pfam ID: PF01536
• Sequence:
  MEAAHFFEGTEKLLEVWFSRQQPDANQGSGDLRTIPRSEWDILLKDVQCSIISVTKTDKQ
  EAYVLSESSMFVSKRRFILKTCGTTLLLKALVPLLKLARDYSGFDSIQSFFYSRKNFMKP
  SHQGYPHRNFQEEIEFLNAIFPNGAAYCMGRMNSDCWYLYTLDFPESRVISQPDQTLEIL
  MSELDPAVMDQFYMKDGVTAKDVTRESGIRDLIPGSVIDATMFNPCGYSMNGMKSDGTYW
  TIHITPEPEFSYVSFETNLSQTSYDDLIRKVVEVFKPGKFVTTLFVNQSSKCRTVLASPQ
  KIEGFKRLDCQSAMFNDYNFVFTSFAKKQQQQQS
• Function: Essential for biosynthesis of the polyamines spermidine and spermine. Promotes maintenance and self-renewal of embryonic stem cells, by maintaining spermine levels.
• KEGG Pathway:
  Cysteine and methionine metabolism (hsa00270)
  Arginine and proline metabolism (hsa00330)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Metabolism of polyamines (R-HSA-351202)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Ifosfamide	DMCT3I8	Approved	S-adenosylmethionine decarboxylase proenzyme (AMD1) increases the Metabolic disorder ADR of Ifosfamide.	[19]
Chlorpromazine	DMBGZI3	Phase 3 Trial	S-adenosylmethionine decarboxylase proenzyme (AMD1) increases the Metabolic disorder ADR of Chlorpromazine.	[19]

18 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 S-adenosylmethionine decarboxylase proenzyme (AMD1).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of S-adenosylmethionine decarboxylase proenzyme (AMD1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of S-adenosylmethionine decarboxylase proenzyme (AMD1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of S-adenosylmethionine decarboxylase proenzyme (AMD1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of S-adenosylmethionine decarboxylase proenzyme (AMD1).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of S-adenosylmethionine decarboxylase proenzyme (AMD1).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of S-adenosylmethionine decarboxylase proenzyme (AMD1).	[8]
Marinol	DM70IK5	Approved	Marinol decreases the expression of S-adenosylmethionine decarboxylase proenzyme (AMD1).	[9]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of S-adenosylmethionine decarboxylase proenzyme (AMD1).	[10]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of S-adenosylmethionine decarboxylase proenzyme (AMD1).	[11]
Bicalutamide	DMZMSPF	Approved	Bicalutamide increases the expression of S-adenosylmethionine decarboxylase proenzyme (AMD1).	[12]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the activity of S-adenosylmethionine decarboxylase proenzyme (AMD1).	[13]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of S-adenosylmethionine decarboxylase proenzyme (AMD1).	[3]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of S-adenosylmethionine decarboxylase proenzyme (AMD1).	[15]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of S-adenosylmethionine decarboxylase proenzyme (AMD1).	[16]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of S-adenosylmethionine decarboxylase proenzyme (AMD1).	[17]
Rutin	DMEHRAJ	Investigative	Rutin decreases the expression of S-adenosylmethionine decarboxylase proenzyme (AMD1).	[18]
Piceatannol	DMYOP45	Investigative	Piceatannol decreases the activity of S-adenosylmethionine decarboxylase proenzyme (AMD1).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the methylation of S-adenosylmethionine decarboxylase proenzyme (AMD1).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of S-adenosylmethionine decarboxylase proenzyme (AMD1).	[14]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [3] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [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] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [9] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [10] Nicotinic modulation of gene expression in SH-SY5Y neuroblastoma cells. Brain Res. 2006 Oct 20;1116(1):39-49.
• [11] Mechanisms of indomethacin-induced alterations in the choline phospholipid metabolism of breast cancer cells. Neoplasia. 2006 Sep;8(9):758-71.
• [12] Casodex treatment induces hypoxia-related gene expression in the LNCaP prostate cancer progression model. BMC Urol. 2005 Mar 24;5:5.
• [13] Resveratrol-induced modification of polyamine metabolism is accompanied by induction of c-Fos. Carcinogenesis. 2003 Mar;24(3):469-74. doi: 10.1093/carcin/24.3.469.
• [14] 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.
• [15] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [16] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [17] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [18] Combination of metabolomics and network pharmacology analysis to decipher the mechanisms of total flavonoids of Litchi seed against prostate cancer. J Pharm Pharmacol. 2023 Jul 5;75(7):951-968. doi: 10.1093/jpp/rgad035.
• [19] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.