Record Information |
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Version | 2.0 |
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Creation Date | 2009-07-21 20:28:19 UTC |
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Update Date | 2014-12-24 20:25:54 UTC |
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Accession Number | T3D2977 |
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Identification |
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Common Name | Vigabatrin |
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Class | Small Molecule |
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Description | Vigabatrin is only found in individuals that have used or taken this drug. It is an analogue of gamma-aminobutyric acid. It is an irreversible inhibitor of 4-aminobutyrate transaminase, the enzyme responsible for the catabolism of gamma-aminobutyric acid. (From Martindale The Extra Pharmacopoeia, 31st ed)It is believed that vigabatrin increases brain concentrations of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in the CNS, by irreversibly inhibiting enzymes that catabolize GABA (gamma-aminobutyric acid transaminase GABA-T) or block the reuptake of GABA into glia and nerve endings. Vigabatrin may also work by suppressing repetitive neuronal firing through inhibition of voltage-sensitive sodium channels. |
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Compound Type | - Amine
- Anticonvulsant
- Drug
- Enzyme Inhibitor
- GABA Agent
- Metabolite
- Organic Compound
- Synthetic Compound
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Chemical Structure | |
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Synonyms | Synonym | 4-Amino-5-hexenoic acid | gamma-Vinyl GABA | gamma-Vinyl-gamma-aminobutyric acid | GVG | Sabril | Sabrilan | Sabrilex | Vigabatrina | Vigabatrine | Vigabatrinum |
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Chemical Formula | C6H11NO2 |
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Average Molecular Mass | 129.157 g/mol |
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Monoisotopic Mass | 129.079 g/mol |
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CAS Registry Number | 60643-86-9 |
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IUPAC Name | 4-aminohex-5-enoic acid |
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Traditional Name | vigabatrin |
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SMILES | NC(CCC(O)=O)C=C |
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InChI Identifier | InChI=1/C6H11NO2/c1-2-5(7)3-4-6(8)9/h2,5H,1,3-4,7H2,(H,8,9) |
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InChI Key | InChIKey=PJDFLNIOAUIZSL-UHFFFAOYNA-N |
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Chemical Taxonomy |
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Description | belongs to the class of organic compounds known as gamma amino acids and derivatives. These are amino acids having a (-NH2) group attached to the gamma carbon atom. |
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Kingdom | Organic compounds |
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Super Class | Organic acids and derivatives |
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Class | Carboxylic acids and derivatives |
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Sub Class | Amino acids, peptides, and analogues |
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Direct Parent | Gamma amino acids and derivatives |
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Alternative Parents | |
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Substituents | - Gamma amino acid or derivatives
- Medium-chain fatty acid
- Amino fatty acid
- Unsaturated fatty acid
- Fatty acyl
- Fatty acid
- Amino acid
- Carboxylic acid
- Monocarboxylic acid or derivatives
- Amine
- Hydrocarbon derivative
- Primary amine
- Organooxygen compound
- Organonitrogen compound
- Organic oxide
- Primary aliphatic amine
- Organopnictogen compound
- Organic oxygen compound
- Carbonyl group
- Organic nitrogen compound
- Aliphatic acyclic compound
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Molecular Framework | Aliphatic acyclic compounds |
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External Descriptors | |
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Biological Properties |
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Status | Detected and Not Quantified |
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Origin | Exogenous |
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Cellular Locations | - Cytoplasm
- Extracellular
- Membrane
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Biofluid Locations | Not Available |
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Tissue Locations | Not Available |
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Pathways | Not Available |
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Applications | |
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Biological Roles | |
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Chemical Roles | |
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Physical Properties |
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State | Solid |
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Appearance | White powder. |
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Experimental Properties | Property | Value |
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Melting Point | Not Available | Boiling Point | Not Available | Solubility | 55.1 mg/mL | LogP | -2.16 |
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Predicted Properties | |
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Spectra |
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Spectra | Spectrum Type | Description | Splash Key | View |
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Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive | splash10-0a6r-9000000000-ed9483c326234125f4ad | JSpectraViewer | Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positive | splash10-004i-3900000000-6c317e49ab8cc532a558 | JSpectraViewer | Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive | Not Available | JSpectraViewer | Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive | Not Available | JSpectraViewer | Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive | Not Available | JSpectraViewer | Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS (TMS_1_2) - 70eV, Positive | Not Available | JSpectraViewer | Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS (TBDMS_1_1) - 70eV, Positive | Not Available | JSpectraViewer | Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS (TBDMS_1_2) - 70eV, Positive | Not Available | JSpectraViewer | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QFT , positive | splash10-00di-9400000000-0215823a9ba364cc48cb | JSpectraViewer | MoNA | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QFT , positive | splash10-00di-9400000000-c7d21d36dfb8e7079ee2 | JSpectraViewer | MoNA | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QFT , positive | splash10-00di-9200000000-e0c504f980ef5bbc0501 | JSpectraViewer | MoNA | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QFT , positive | splash10-00di-9000000000-e1b2ea8d5a2da84a5a64 | JSpectraViewer | MoNA | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QFT , positive | splash10-00di-9000000000-52958176067fd9bae916 | JSpectraViewer | MoNA | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QFT , positive | splash10-00di-9000000000-263da4b132ca66986967 | JSpectraViewer | MoNA | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QFT , positive | splash10-01b9-9000000000-1f8826cc32ef269c1a7c | JSpectraViewer | MoNA | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QFT , positive | splash10-014i-9000000000-32306e2f90cd529accc7 | JSpectraViewer | MoNA | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QFT , positive | splash10-0gb9-9000000000-aefa9f2682087c7b78ed | JSpectraViewer | MoNA | LC-MS/MS | LC-MS/MS Spectrum - 90V, Positive | splash10-00di-9000000000-2e8122bd9fa086c48c81 | JSpectraViewer | MoNA | LC-MS/MS | LC-MS/MS Spectrum - 60V, Positive | splash10-00di-9000000000-c89fa23e4a66cb1fda0e | JSpectraViewer | MoNA | LC-MS/MS | LC-MS/MS Spectrum - 75V, Positive | splash10-00di-9000000000-ee55e365ddd88597a424 | JSpectraViewer | MoNA | LC-MS/MS | LC-MS/MS Spectrum - 120V, Positive | splash10-01b9-9000000000-59ee75afd49600cf9595 | JSpectraViewer | MoNA | LC-MS/MS | LC-MS/MS Spectrum - 150V, Positive | splash10-014i-9000000000-32306e2f90cd529accc7 | JSpectraViewer | MoNA | LC-MS/MS | LC-MS/MS Spectrum - 45V, Positive | splash10-00di-9200000000-6c0ed7a9357b20c8ddec | JSpectraViewer | MoNA | LC-MS/MS | LC-MS/MS Spectrum - 30V, Positive | splash10-00di-9400000000-67f3710d9b1a8968c528 | JSpectraViewer | MoNA | LC-MS/MS | LC-MS/MS Spectrum - 180V, Positive | splash10-0gb9-9000000000-aefa9f2682087c7b78ed | JSpectraViewer | MoNA | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 10V, Positive | splash10-01q9-3900000000-5bf6d0079fa19a719d28 | JSpectraViewer | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 20V, Positive | splash10-01q9-9400000000-1d89cce66d591018b8b6 | JSpectraViewer | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 40V, Positive | splash10-0gb9-9000000000-25ce972a542597293a60 | JSpectraViewer | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 10V, Negative | splash10-004i-2900000000-14e6a479b3001860431b | JSpectraViewer | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 20V, Negative | splash10-004i-7900000000-fd7f3b3f074734314a87 | JSpectraViewer | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 40V, Negative | splash10-0a4l-9100000000-db0d4ab6ed018a7e6a3f | JSpectraViewer | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 10V, Positive | splash10-001i-9400000000-6179584a37d7e78d7234 | JSpectraViewer | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 20V, Positive | splash10-014i-9000000000-ff84f320ba47dd80531b | JSpectraViewer | 1D NMR | 1H NMR Spectrum | Not Available | JSpectraViewer | 1D NMR | 13C NMR Spectrum | Not Available | JSpectraViewer | 1D NMR | 1H NMR Spectrum | Not Available | JSpectraViewer | 1D NMR | 13C NMR Spectrum | Not Available | JSpectraViewer | 1D NMR | 1H NMR Spectrum | Not Available | JSpectraViewer | 1D NMR | 13C NMR Spectrum | Not Available | JSpectraViewer | 1D NMR | 1H NMR Spectrum | Not Available | JSpectraViewer | 1D NMR | 13C NMR Spectrum | Not Available | JSpectraViewer | 1D NMR | 1H NMR Spectrum | Not Available | JSpectraViewer | 1D NMR | 13C NMR Spectrum | Not Available | JSpectraViewer | 1D NMR | 1H NMR Spectrum | Not Available | JSpectraViewer | 1D NMR | 13C NMR Spectrum | Not Available | JSpectraViewer | 1D NMR | 1H NMR Spectrum | Not Available | JSpectraViewer | 1D NMR | 13C NMR Spectrum | Not Available | JSpectraViewer | 1D NMR | 1H NMR Spectrum | Not Available | JSpectraViewer | 1D NMR | 13C NMR Spectrum | Not Available | JSpectraViewer | 1D NMR | 1H NMR Spectrum | Not Available | JSpectraViewer | 1D NMR | 13C NMR Spectrum | Not Available | JSpectraViewer | 1D NMR | 1H NMR Spectrum | Not Available | JSpectraViewer | 1D NMR | 13C NMR Spectrum | Not Available | JSpectraViewer |
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Toxicity Profile |
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Route of Exposure | Rapidly absorbed following oral administration, absorption is comparable between neonates, infants, and children.
Cmax, 50 mg/kg dose, neonates= 14 mg/L;
Tmax, 50 mg/kg dose, neonates = 2.1 hours;
However, extent of absorption is higher and elimination half life is longer in neonates compared to children and infants. This is because neonates have reduced renal function compared to the aforementioned population groups.
AUC, 50 mg/kg dose, neonates = 142.6 ± 44.0 mg/L/hr;
Food may slightly decrease the rate (Cmax decreased by 33%, Tmax increased to 2 hours), but not the extent of absorption. Furthermore, vigabatrin does not cross the blood-brain-barrier well, thus high doses are needed.
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Mechanism of Toxicity | Vigabatrin increases brain concentrations of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in the CNS, by irreversibly inhibiting enzymes that catabolize GABA (gamma-aminobutyric acid transaminase, GABA-T). Duration of action is determined by rate of GABA-T re-synthesis. Vigabatrin may also work by suppressing repetitive neuronal firing through inhibition of voltage-sensitive sodium channels. Although administered as a racemic mixture, only the S(+) enantiomer is pharmacologically active. |
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Metabolism | Almost no metabolic transformation. Does not induce the hepatic cytochrome P450 system.
Route of Elimination: Eliminated primarily through renal excretion as unchanged drugs (80%).
Half Life: Neonates, 50 mg/kg = 7.5 ± 2.1 hours (due to reduced renal function);
Infants = 5.7 hours;
Adults = 7.5 hours;
Elderly = 12 - 13 hours
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Toxicity Values | LD50, oral, rat: 3000 mg/kg |
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Lethal Dose | Not Available |
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Carcinogenicity (IARC Classification) | No indication of carcinogenicity to humans (not listed by IARC). |
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Uses/Sources | For use as an adjunct in treatment resistant epilepsy, refractory complex partial seizures, and secondary generalized seizures. It is also used as monotherapy in infantile spasms in West syndrome. |
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Minimum Risk Level | Not Available |
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Health Effects | May cause a potentially dangerous rash that may develop into Stevens Johnson syndrome, an extremely rare but potentially fatal skin disease. |
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Symptoms | Not Available |
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Treatment | Not Available |
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Normal Concentrations |
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| Not Available |
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Abnormal Concentrations |
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| Not Available |
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External Links |
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DrugBank ID | DB01080 |
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HMDB ID | HMDB15212 |
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PubChem Compound ID | 5665 |
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ChEMBL ID | CHEMBL89598 |
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ChemSpider ID | 5463 |
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KEGG ID | C07500 |
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UniProt ID | Not Available |
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OMIM ID | |
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ChEBI ID | 63638 |
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BioCyc ID | VIGABATRIN |
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CTD ID | Not Available |
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Stitch ID | Vigabatrin |
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PDB ID | 1OHW |
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ACToR ID | Not Available |
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Wikipedia Link | Vigabatrin |
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References |
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Synthesis Reference | Not Available |
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MSDS | Link |
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General References | - Gram L, Larsson OM, Johnsen A, Schousboe A: Experimental studies of the influence of vigabatrin on the GABA system. Br J Clin Pharmacol. 1989;27 Suppl 1:13S-17S. [2757904 ]
- Browne TR: Pharmacokinetics of antiepileptic drugs. Neurology. 1998 Nov;51(5 Suppl 4):S2-7. [9818917 ]
- Lindberger M, Luhr O, Johannessen SI, Larsson S, Tomson T: Serum concentrations and effects of gabapentin and vigabatrin: observations from a dose titration study. Ther Drug Monit. 2003 Aug;25(4):457-62. [12883229 ]
- Zwanzger P, Baghai TC, Schuele C, Strohle A, Padberg F, Kathmann N, Schwarz M, Moller HJ, Rupprecht R: Vigabatrin decreases cholecystokinin-tetrapeptide (CCK-4) induced panic in healthy volunteers. Neuropsychopharmacology. 2001 Nov;25(5):699-703. [11682253 ]
- Tulloch JK, Carr RR, Ensom MH: A systematic review of the pharmacokinetics of antiepileptic drugs in neonates with refractory seizures. J Pediatr Pharmacol Ther. 2012 Jan;17(1):31-44. doi: 10.5863/1551-6776-17.1.31. [23118657 ]
- Clayton LM, Stern WM, Newman WD, Sander JW, Acheson J, Sisodiya SM: Evolution of visual field loss over ten years in individuals taking vigabatrin. Epilepsy Res. 2013 Aug;105(3):262-71. doi: 10.1016/j.eplepsyres.2013.02.014. Epub 2013 Mar 28. [23541931 ]
- Hawker DD, Silverman RB: Synthesis and evaluation of novel heteroaromatic substrates of GABA aminotransferase. Bioorg Med Chem. 2012 Oct 1;20(19):5763-73. doi: 10.1016/j.bmc.2012.08.009. Epub 2012 Aug 16. [22944334 ]
- Drugs.com [Link]
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Gene Regulation |
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Up-Regulated Genes | Not Available |
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Down-Regulated Genes | Not Available |
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