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Namespace Prefixes

PrefixIRI
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n19http://linked.opendata.cz/resource/atc/
n17http://linked.opendata.cz/ontology/sukl/drug/

Statements

Subject Item
n2:DB06813
rdf:type
n3:Drug
n3:description
Pralatrexate is an antimetabolite for the treatment of relapsed or refractory peripheral T-cell lymphoma. It is more efficiently retained in cancer cells than methotrexate. FDA approved on September 24, 2009.
n3:dosage
n20:271B556B-363D-11E5-9242-09173F13E4C5
n3:generalReferences
# Shimanovsky A, Dasanu CA: Pralatrexate : evaluation of clinical efficacy and toxicity in T-cell lymphoma. Expert Opin Pharmacother. 2013 Mar;14(4):515-23. doi: 10.1517/14656566.2013.770474. Epub 2013 Feb 14. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/23409799 # Gonen N, Assaraf YG: Antifolates in cancer therapy: structure, activity and mechanisms of drug resistance. Drug Resist Updat. 2012 Aug;15(4):183-210. doi: 10.1016/j.drup.2012.07.002. Epub 2012 Aug 23. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/22921318 # Rodd AL, Ververis K, Karagiannis TC: Safety and efficacy of pralatrexate in the management of relapsed or refractory peripheral T-cell lymphoma. Clin Med Insights Oncol. 2012;6:305-14. doi: 10.4137/CMO.S8536. Epub 2012 Aug 21. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/23032692
n3:group
approved
n3:halfLife
12-18 hours
n3:indication
Treatment of relapsed or refractory peripheral T-cell lymphoma.
owl:sameAs
n7:DB06813
dcterms:title
Pralatrexate
adms:identifier
n10:71223 n11:48818-001-01 n12:Pralatrexate n13:DB06813 n14:D05589
n3:mechanismOfAction
The selectivity of pralatrexate for cancer cells is based upon the observation that cancer cells generally have an overexpression of reduced folate carrier protein-1 (RTC-1) compared to normal somatic cells. This carrier protein allows the entrance of pralatrexate into the cell. Upon entering the cell, folypolyglutamate synthase FPGS catalyzes the polyglutamination of pralatrexate so that it is retained inside the cell. Once inside, pralatrexate competitively inhibits dihydrofolate reductase (DHFR) and thymidylate synthase. Subsequent depletion of thymidine monophosphate (TMP) occurs so that the cancer cell is unable to synthesize DNA and RNA. As a result, the cancer cell cannot proliferate and is forced to undergo apoptosis. Pralatrexate is more effective against cells that are actively dividing.
n3:patent
n4:6028071 n4:7622470 n4:8299078
n3:routeOfElimination
35% of drug is excreted unchanged in the urine (no difference between R- and S- pralatrexate). May be some net renal tubular excretion.
n3:synonym
PDX N-(4-(1-((2,4-Diamino-6-pteridinyl)methyl)-3-butynyl)benzoyl)-L-glutamic acid (2S)-2-({4-[1-(2,4-diaminopteridin-6-yl)pent-4-yn-2-yl]benzoyl}amino)pentanedioic acid (2S)-2-((4-((1RS)-1-((2,4-diaminopteridin-6-yl)methyl)but-3-ynyl)benzoyl)amino)pentanedioic acid Pralatrexato HSDB 7786 Folotyn 10-Propargyl-10-deazaaminopterin Pralatrexatum
n3:toxicity
Mucositis is the dose-limiting toxicity. Folic acid and vitamin B12 supplements do not prevent mucositis from happening.
n3:volumeOfDistribution
Vss, R-pralatrexate = 37 L Vss, S-pralatrexate = 105 L
n17:hasAHFSCode
n18:10-00%20
n3:proteinBinding
67 - 86% bound to plasma protein, albumin is the major binder. Does not significantly displace substrates from proteins.
foaf:page
n16:pralatrexate.html n21:folotyn-drug.htm
n3:IUPAC-Name
n5:271B5570-363D-11E5-9242-09173F13E4C5
n3:InChI
n5:271B5576-363D-11E5-9242-09173F13E4C5
n3:Molecular-Formula
n5:271B5575-363D-11E5-9242-09173F13E4C5
n3:Molecular-Weight
n5:271B5572-363D-11E5-9242-09173F13E4C5
n3:Monoisotopic-Weight
n5:271B5573-363D-11E5-9242-09173F13E4C5
n3:SMILES
n5:271B5574-363D-11E5-9242-09173F13E4C5
n3:Water-Solubility
n5:271B556E-363D-11E5-9242-09173F13E4C5
n3:logP
n5:271B556F-363D-11E5-9242-09173F13E4C5 n5:271B556C-363D-11E5-9242-09173F13E4C5
n3:logS
n5:271B556D-363D-11E5-9242-09173F13E4C5
n17:hasATCCode
n19:L01BA05
n3:H-Bond-Acceptor-Count
n5:271B557C-363D-11E5-9242-09173F13E4C5
n3:H-Bond-Donor-Count
n5:271B557D-363D-11E5-9242-09173F13E4C5
n3:InChIKey
n5:271B5577-363D-11E5-9242-09173F13E4C5
n3:Polar-Surface-Area--PSA-
n5:271B5578-363D-11E5-9242-09173F13E4C5
n3:Polarizability
n5:271B557A-363D-11E5-9242-09173F13E4C5
n3:Refractivity
n5:271B5579-363D-11E5-9242-09173F13E4C5
n3:Rotatable-Bond-Count
n5:271B557B-363D-11E5-9242-09173F13E4C5
n3:absorption
Pralatrexate demonstrates linear pharmacokinetics with a multiphasic decline with both diasteromers over dose range of 30-325 mg/m^2. Bioavailability, nonformulated preparation = 13 - 20%
n3:affectedOrganism
Humans and other mammals
n3:casRegistryNumber
146464-95-1
n3:clearance
R- pralatrexate = 191 mL/min S- pralatrexate = 417 mL/min Mean clearance of both enantiomers is 220 mL/min.
n3:Bioavailability
n5:271B5582-363D-11E5-9242-09173F13E4C5
n3:Ghose-Filter
n5:271B5584-363D-11E5-9242-09173F13E4C5
n3:MDDR-Like-Rule
n5:271B5585-363D-11E5-9242-09173F13E4C5
n3:Number-of-Rings
n5:271B5581-363D-11E5-9242-09173F13E4C5
n3:Physiological-Charge
n5:271B5580-363D-11E5-9242-09173F13E4C5
n3:Rule-of-Five
n5:271B5583-363D-11E5-9242-09173F13E4C5
n3:Traditional-IUPAC-Name
n5:271B5571-363D-11E5-9242-09173F13E4C5
n3:pKa--strongest-acidic-
n5:271B557E-363D-11E5-9242-09173F13E4C5
n3:pKa--strongest-basic-
n5:271B557F-363D-11E5-9242-09173F13E4C5