Target Information

Target General Infomation
Target ID
T55922
Former ID
TTDR00414
Target Name
S-adenosylmethioninedecarboxylase proenzyme
Gene Name
AMD1
Synonyms
AdoMetDC; S-adenosylmethioninedecarboxylase; SamDC; AMD1
Target Type
Clinical Trial
Disease Burns and burn infection [ICD9: 001-139; ICD10: A00-B99]
Head and neck cancer [ICD9: 140-149, 140-229; ICD10: C07-C14, C32-C33]
Pneumocystis carinii infection [ICD10: B59]
Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48]
Function
Essential for biosynthesis of the polyamines spermidine and spermine. Promotes maintenance and self-renewal of embryonic stem cells, by maintaining spermine levels (By similarity).
BioChemical Class
Carbon-carbon lyase
Target Validation
T55922
UniProt ID
P17707
EC Number
EC 4.1.1.50
Sequence
MEAAHFFEGTEKLLEVWFSRQQPDANQGSGDLRTIPRSEWDILLKDVQCSIISVTKTDKQ
EAYVLSESSMFVSKRRFILKTCGTTLLLKALVPLLKLARDYSGFDSIQSFFYSRKNFMKP
SHQGYPHRNFQEEIEFLNAIFPNGAAYCMGRMNSDCWYLYTLDFPESRVISQPDQTLEIL
MSELDPAVMDQFYMKDGVTAKDVTRESGIRDLIPGSVIDATMFNPCGYSMNGMKSDGTYW
TIHITPEPEFSYVSFETNLSQTSYDDLIRKVVEVFKPGKFVTTLFVNQSSKCRTVLASPQ
KIEGFKRLDCQSAMFNDYNFVFTSFAKKQQQQQS
Drugs and Mode of Action
Drug(s) SAM486A Drug Info Phase 2 Solid tumours [535793], [540731]
Putrescine Drug Info Discontinued in Phase 2 Burns and burn infection [539518], [547142]
CGP-40215A Drug Info Terminated Pneumocystis carinii infection [534214]
MGBG Drug Info Terminated Head and neck cancer [525957], [535793]
Inhibitor 5'-([(Z)-4-amino-2-butenyl]methylamino)-5'-deoxyadenosine Drug Info [535793]
5'-Deoxy-5'-(N,N-dimethylamino)-8-methyladenosine Drug Info [529959]
5'-Deoxy-5'-(N,N-dimethylamino)adenosine Drug Info [529959]
5'-Deoxy-5'-dimethylsulfonioadenosine chloride Drug Info [529959]
5'-deoxy-5'-[(3-hydrazinopropyl)methylamino]adenosine Drug Info [535793]
Guanylhydrazone Drug Info [538021]
Hydroxyalanine Drug Info [551391]
MGBG Drug Info [535032], [535955]
Putrescine Drug Info [551393]
SAM486A Drug Info [535032]
Tris(Hydroxymethyl)Aminomethane Drug Info [551393]
[(2-aminooxyethyl)methylamino]-5'-deoxyadenosine Drug Info [529959]
Modulator CGP-40215A Drug Info [534214], [535793]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
BioCyc Pathway Methionine salvage cycle III
Spermine biosynthesis
Spermidine biosynthesis
KEGG Pathway Cysteine and methionine metabolism
Arginine and proline metabolism
Metabolic pathways
NetPath Pathway EGFR1 Signaling Pathway
PathWhiz Pathway Spermidine and Spermine Biosynthesis
Methionine Metabolism
WikiPathways Metabolism of amino acids and derivatives
References
Ref 525957Spermine deficiency resulting from targeted disruption of the spermine synthase gene in embryonic stem cells leads to enhanced sensitivity to antiproliferative drugs. Mol Pharmacol. 2001 Feb;59(2):231-8.
Ref 534214Antileishmanial effect of a potent S-adenosylmethionine decarboxylase inhibitor: CGP 40215A. Pharmacol Res. 1996 Jan;33(1):67-70.
Ref 535793S-adenosylmethionine decarboxylase as an enzyme target for therapy. Pharmacol Ther. 1992 Dec;56(3):359-77.
Ref 539518(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2388).
Ref 540731(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5268).
Ref 547142Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800013366)
Ref 529959J Med Chem. 2009 Mar 12;52(5):1388-407.New insights into the design of inhibitors of human S-adenosylmethionine decarboxylase: studies of adenine C8 substitution in structural analogues of S-adenosylmethionine.
Ref 534214Antileishmanial effect of a potent S-adenosylmethionine decarboxylase inhibitor: CGP 40215A. Pharmacol Res. 1996 Jan;33(1):67-70.
Ref 535032A 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.
Ref 535793S-adenosylmethionine decarboxylase as an enzyme target for therapy. Pharmacol Ther. 1992 Dec;56(3):359-77.
Ref 535955New S-adenosylmethionine decarboxylase inhibitors with potent antitumor activity. Cancer Res. 1992 Sep 1;52(17):4712-8.
Ref 538021CGP 48664, a potent and specific S-adenosylmethionine decarboxylase inhibitor: effects on regulation and stability of the enzyme. Biochem J. 1997 Feb 15;322 ( Pt 1):297-302.
Ref 551391DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-4. Nucleic Acids Res. 2011 January
Ref 551393How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.

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