Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTBFROQ)

• DTT Name: S-adenosylmethionine decarboxylase proenzyme (AMD1)
• Synonyms: SamDC; S-adenosylmethioninedecarboxylase; AdoMetDC; AMD
• Gene Name: AMD1
• DTT Type: Successful target; [1]
• BioChemical Class: Carbon-carbon lyase
• UniProt ID: DCAM_HUMAN
• TTD ID: T55922
• EC Number: EC 4.1.1.50
• Sequence:
  MEAAHFFEGTEKLLEVWFSRQQPDANQGSGDLRTIPRSEWDILLKDVQCSIISVTKTDKQ
  EAYVLSESSMFVSKRRFILKTCGTTLLLKALVPLLKLARDYSGFDSIQSFFYSRKNFMKP
  SHQGYPHRNFQEEIEFLNAIFPNGAAYCMGRMNSDCWYLYTLDFPESRVISQPDQTLEIL
  MSELDPAVMDQFYMKDGVTAKDVTRESGIRDLIPGSVIDATMFNPCGYSMNGMKSDGTYW
  TIHITPEPEFSYVSFETNLSQTSYDDLIRKVVEVFKPGKFVTTLFVNQSSKCRTVLASPQ
  KIEGFKRLDCQSAMFNDYNFVFTSFAKKQQQQQS
• Function: Promotes maintenance and self-renewal of embryonic stem cells, by maintaining spermine levels. Essential for biosynthesis of the polyamines spermidine and spermine.
• 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 DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tromethamine	DMOBLGK	Acidosis	5C73	Approved	[1]

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ORG 34517/34850	DMR3P98	Mood disorder	6A60-6E23	Phase 2	[2]

3 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Putrescine	DMWE6V1	Burn and burn infection	ND90-NE2Z	Discontinued in Phase 2	[1]
CGP-40215A	DM69YWS	Pneumocystis pneumonia	CA40.20	Terminated	[3]
MGBG	DM9GOT6	Head and neck cancer	2D42	Terminated	[2]

7 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
5'-([(Z)-4-amino-2-butenyl]methylamino)-5'-deoxyadenosine	DMT6D5V	Discovery agent	N.A.	Investigative	[4]
5'-Deoxy-5'-(N,N-dimethylamino)-8-methyladenosine	DMOHSY0	Discovery agent	N.A.	Investigative	[5]
5'-Deoxy-5'-(N,N-dimethylamino)adenosine	DMF7JPO	Discovery agent	N.A.	Investigative	[5]
5'-Deoxy-5'-dimethylsulfonioadenosine chloride	DM1NAMK	Discovery agent	N.A.	Investigative	[5]
5'-deoxy-5'-[(3-hydrazinopropyl)methylamino]adenosine	DM6HGUL	Discovery agent	N.A.	Investigative	[4]
Hydroxyalanine	DM5HWZY	Discovery agent	N.A.	Investigative	[6]
[(2-aminooxyethyl)methylamino]-5'-deoxyadenosine	DM3WDOY	Discovery agent	N.A.	Investigative	[5]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Head and neck cancer	2C82	Head and neck tissue	4.41E-05	0.37	0.61

References

• [1] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [2] A phase I study of a new polyamine biosynthesis inhibitor, SAM486A, in cancer patients with solid tumours. Br J Cancer. 2000 Sep;83(5):594-601.
• [3] Antileishmanial effect of a potent S-adenosylmethionine decarboxylase inhibitor: CGP 40215A. Pharmacol Res. 1996 Jan;33(1):67-70.
• [4] S-adenosylmethionine decarboxylase as an enzyme target for therapy. Pharmacol Ther. 1992 Dec;56(3):359-77.
• [5] New insights into the design of inhibitors of human S-adenosylmethionine decarboxylase: studies of adenine C8 substitution in structural analogues ... J Med Chem. 2009 Mar 12;52(5):1388-407.
• [6] DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41.