Target Information

Target General Infomation
Target ID
T60366
Former ID
TTDS00313
Target Name
Ornithine decarboxylase
Gene Name
ODC1
Synonyms
ODC; ODC1
Target Type
Clinical Trial
Disease African trypanosomiasis [ICD9: 86.5; ICD10: B56]
Burns and burn infection [ICD9: 001-139; ICD10: A00-B99]
Head and neck cancer [ICD9: 140-149, 140-229; ICD10: C07-C14, C32-C33]
Trypanosoma brucei gambiense infection [ICD9: 86.5; ICD10: B56]
Function
Key enzyme of polyamine biosynthesis that converts ornithine into putrescine, which is the precursor for the polyamines, spermidine and spermine.
BioChemical Class
Carbon-carbon lyase
Target Validation
T60366
UniProt ID
P11926
EC Number
EC 4.1.1.17
Sequence
MNNFGNEEFDCHFLDEGFTAKDILDQKINEVSSSDDKDAFYVADLGDILKKHLRWLKALP
RVTPFYAVKCNDSKAIVKTLAATGTGFDCASKTEIQLVQSLGVPPERIIYANPCKQVSQI
KYAANNGVQMMTFDSEVELMKVARAHPKAKLVLRIATDDSKAVCRLSVKFGATLRTSRLL
LERAKELNIDVVGVSFHVGSGCTDPETFVQAISDARCVFDMGAEVGFSMYLLDIGGGFPG
SEDVKLKFEEITGVINPALDKYFPSDSGVRIIAEPGRYYVASAFTLAVNIIAKKIVLKEQ
TGSDDEDESSEQTFMYYVNDGVYGSFNCILYDHAHVKPLLQKRPKPDEKYYSSSIWGPTC
DGLDRIVERCDLPEMHVGDWMLFENMGAYTVAAASTFNGFQRPTIYYVMSGPAWQLMQQF
QNPDFPPEVEEQDASTLPVSCAWESGMKRHRAACASASINV
Structure
1D7K; 2ON3; 2OO0; 1F3T; 1QU4; 1SZR; 2TOD
Drugs and Mode of Action
Drug(s) Eflornithine Drug Info Approved African trypanosomiasis [468237], [536135]
Difluoromethylornithine Drug Info Phase 2 Trypanosoma brucei gambiense infection [523970]
DFMO Drug Info Withdrawn from market Discovery agent [545498]
Putrescine Drug Info Discontinued in Phase 2 Burns and burn infection [539518], [547142]
Inhibitor (2R,5R)-delta-methyl-alpha-acetylenic putrescine Drug Info [537732]
1-Amino-3-(aminoxy)-2-propanol Dihydrochloride Drug Info [531018]
3-(Aminooxy)propan-1-amine hydrochloride Drug Info [531018]
3-aminooxy-1-aminopropane Drug Info [528522]
3-methoxy-4-hydroxylonchocarpin Drug Info [525437]
4-hydroxylonchocarpin Drug Info [525437]
Alpha-Difluoromethylornithine Drug Info [551393]
Alpha-monofluoromethyl-3,4-dehydroornithine Drug Info [537732]
Alpha-monofluoromethyl-3,4-dehydroornithine ethyl ester Drug Info [537732]
Alpha-monofluoromethyl-3,4-dehydroornithine methyl ester Drug Info [537732]
AMXT-1501 Drug Info [543400]
APA Drug Info [527450]
DFMO Drug Info [534924]
Difluoromethylornithine Drug Info [537878]
Eflornithine Drug Info [537732]
G418 Drug Info [551393]
LONCHOCARPUSONE Drug Info [525437]
N'-Pyridoxyl-Lysine-5'-Monophosphate Drug Info [551393]
N-Pyridoxyl-Glycine-5-Monophosphate Drug Info [551393]
Putrescine Drug Info [551393]
Pyridoxine-5'-Phosphate Drug Info [551393]
ZAPOTIN Drug Info [528622]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
BioCyc Pathway Putrescine biosynthesis I
NetPath Pathway TCR Signaling Pathway
IL2 Signaling Pathway
TGF_beta_Receptor Signaling Pathway
PANTHER Pathway Ornithine degradation
CCKR signaling map ST
Pathway Interaction Database Validated targets of C-MYC transcriptional activation
PathWhiz Pathway Spermidine and Spermine Biosynthesis
References
Ref 468237(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: 5176).
Ref 523970ClinicalTrials.gov (NCT01636128) Urinary Biomarker Study With Sulindac and Difluoromethylornithine. U.S. National Institutes of Health.
Ref 536135Opportunities and challenges in antiparasitic drug discovery. Nat Rev Drug Discov. 2005 Sep;4(9):727-40.
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 545498Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003500)
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 525437J Nat Prod. 1999 Feb;62(2):205-10.New bioactive flavonoids and stilbenes in cub?| resin insecticide.
Ref 5274502-substituted 3-(aminooxy)propanamines as inhibitors of ornithine decarboxylase: synthesis and biological activity. J Med Chem. 1992 Apr 17;35(8):1339-44.
Ref 528522Antimicrob Agents Chemother. 2007 Feb;51(2):528-34. Epub 2006 Nov 13.Antileishmanial effect of 3-aminooxy-1-aminopropane is due to polyamine depletion.
Ref 528622J Med Chem. 2007 Jan 25;50(2):350-5.Synthesis and cancer chemopreventive activity of zapotin, a natural product from Casimiroa edulis.
Ref 531018Bioorg Med Chem Lett. 2010 Aug 1;20(15):4364-6. Epub 2010 Jun 17.Selective delivery of 2-hydroxy APA to Trypanosoma brucei using the melamine motif.
Ref 534924X-ray structure of ornithine decarboxylase from Trypanosoma brucei: the native structure and the structure in complex with alpha-difluoromethylornithine. Biochemistry. 1999 Nov 16;38(46):15174-84.
Ref 537732Plasmodium falciparum and Plasmodium berghei: effects of ornithine decarboxylase inhibitors on erythrocytic schizogony. Exp Parasitol. 1987 Oct;64(2):237-43.
Ref 537878An inhibitor of polyamine biosynthesis impairs human polymorphonuclear leukocyte priming by tumor necrosis factor alpha. J Leukoc Biol. 1995 Feb;57(2):282-6.
Ref 543400(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. (Target id: 1276).
Ref 551393How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.

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