Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4N5MDP)

• DOT Name: Spermidine synthase (SRM)
• Synonyms: SPDSY; EC 2.5.1.16; Putrescine aminopropyltransferase
• Gene Name: SRM
• Related Disease:
  Alzheimer disease
  B-cell lymphoma
  Burkitt lymphoma
  Cardiac disease
  Cardiovascular disease
  Chagas disease
  Cryptococcosis
  Depression
  Hepatocellular carcinoma
  High blood pressure
  Lung adenocarcinoma
  Obsessive compulsive disorder
  Osteoporosis
  Schizophrenia
  Syndromic X-linked intellectual disability Snyder type
  Synovitis
  Age-related macular degeneration
  Prostate cancer
  Prostate carcinoma
  Advanced cancer
  Neoplasm
  Osteoarthritis
• UniProt ID: SPEE_HUMAN
• PDB ID: 2O05; 2O06; 2O07; 2O0L; 3RW9
• EC Number: 2.5.1.16
• Pfam ID: PF17284 ; PF01564
• Sequence:
  MEPGPDGPAASGPAAIREGWFRETCSLWPGQALSLQVEQLLHHRRSRYQDILVFRSKTYG
  NVLVLDGVIQCTERDEFSYQEMIANLPLCSHPNPRKVLIIGGGDGGVLREVVKHPSVESV
  VQCEIDEDVIQVSKKFLPGMAIGYSSSKLTLHVGDGFEFMKQNQDAFDVIITDSSDPMGP
  AESLFKESYYQLMKTALKEDGVLCCQGECQWLHLDLIKEMRQFCQSLFPVVAYAYCTIPT
  YPSGQIGFMLCSKNPSTNFQEPVQPLTQQQVAQMQLKYYNSDVHRAAFVLPEFARKALND
  VS
• Function: Catalyzes the production of spermidine from putrescine and decarboxylated S-adenosylmethionine (dcSAM). Has a strong preference for putrescine as substrate, and has very low activity towards 1,3-diaminopropane. Has extremely low activity towards spermidine.
• KEGG Pathway:
  Cysteine and methionine metabolism (hsa00270)
  Arginine and proline metabolism (hsa00330)
  Glutathione metabolism (hsa00480)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Metabolism of polyamines (R-HSA-351202)
• BioCyc Pathway: MetaCyc:HS04027-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

22 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Biomarker	[1]
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[2]
Burkitt lymphoma	DIS9D5XU	Strong	Biomarker	[2]
Cardiac disease	DISVO1I5	Strong	Biomarker	[3]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[4]
Chagas disease	DIS8KNVF	Strong	Biomarker	[5]
Cryptococcosis	DISDYDTK	Strong	Biomarker	[6]
Depression	DIS3XJ69	Strong	Genetic Variation	[7]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[8]
High blood pressure	DISY2OHH	Strong	Biomarker	[9]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[10]
Obsessive compulsive disorder	DIS1ZMM2	Strong	Biomarker	[11]
Osteoporosis	DISF2JE0	Strong	Genetic Variation	[12]
Schizophrenia	DISSRV2N	Strong	Biomarker	[13]
Syndromic X-linked intellectual disability Snyder type	DISN836E	Strong	Genetic Variation	[12]
Synovitis	DISW2GPY	Strong	Biomarker	[14]
Age-related macular degeneration	DIS0XS2C	moderate	Biomarker	[15]
Prostate cancer	DISF190Y	moderate	Biomarker	[16]
Prostate carcinoma	DISMJPLE	moderate	Biomarker	[16]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[17]
Neoplasm	DISZKGEW	Limited	Altered Expression	[18]
Osteoarthritis	DIS05URM	Limited	Biomarker	[19]

4 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 Spermidine synthase (SRM).	[20]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Spermidine synthase (SRM).	[34]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Spermidine synthase (SRM).	[35]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Spermidine synthase (SRM).	[36]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Spermidine synthase (SRM).	[21]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Spermidine synthase (SRM).	[22]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Spermidine synthase (SRM).	[23]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Spermidine synthase (SRM).	[24]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Spermidine synthase (SRM).	[25]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Spermidine synthase (SRM).	[26]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Spermidine synthase (SRM).	[27]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Spermidine synthase (SRM).	[22]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Spermidine synthase (SRM).	[28]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Spermidine synthase (SRM).	[29]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Spermidine synthase (SRM).	[30]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Spermidine synthase (SRM).	[31]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Spermidine synthase (SRM).	[25]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Spermidine synthase (SRM).	[32]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Spermidine synthase (SRM).	[33]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Spermidine synthase (SRM).	[37]

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