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Identification
NamePralatrexate
Accession NumberDB06813
TypeSmall Molecule
GroupsApproved
DescriptionPralatrexate 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.
Structure
Thumb
Synonyms
(2S)-2-((4-((1RS)-1-((2,4-diaminopteridin-6-yl)methyl)but-3-ynyl)benzoyl)amino)pentanedioic acid
(2S)-2-({4-[1-(2,4-diaminopteridin-6-yl)pent-4-yn-2-yl]benzoyl}amino)pentanedioic acid
10-Propargyl-10-deazaaminopterin
Folotyn
HSDB 7786
N-(4-(1-((2,4-Diamino-6-pteridinyl)methyl)-3-butynyl)benzoyl)-L-glutamic acid
PDX
Pralatrexato
Pralatrexatum
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
FolotynInjection20 mg/mLIntravenousAllos Therapeutics2009-09-24Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIA8Q8I19Q20
CAS number146464-95-1
WeightAverage: 477.4726
Monoisotopic: 477.176066881
Chemical FormulaC23H23N7O5
InChI KeyOGSBUKJUDHAQEA-WMCAAGNKSA-N
InChI
InChI=1S/C23H23N7O5/c1-2-3-14(10-15-11-26-20-18(27-15)19(24)29-23(25)30-20)12-4-6-13(7-5-12)21(33)28-16(22(34)35)8-9-17(31)32/h1,4-7,11,14,16H,3,8-10H2,(H,28,33)(H,31,32)(H,34,35)(H4,24,25,26,29,30)/t14?,16-/m0/s1
IUPAC Name
(2S)-2-({4-[1-(2,4-diaminopteridin-6-yl)pent-4-yn-2-yl]phenyl}formamido)pentanedioic acid
SMILES
NC1=NC2=NC=C(CC(CC#C)C3=CC=C(C=C3)C(=O)N[C@@H](CCC(O)=O)C(O)=O)N=C2C(N)=N1
Pharmacology
IndicationTreatment of relapsed or refractory peripheral T-cell lymphoma.
Structured Indications
PharmacodynamicsPralatrexate is a 10-deazaaminopterin analogue of methotrexate. Compared to methotrexate, pralatrexate binds to RTC-1 with 10-times the affinity and is a more potent substrate for FPGS. As a result, pralatrexate is better internalized and retained in cancer cells and is more cytotoxic. Km, pralatrexate = 0.3 μmol/L; Km, methotrexate = 4.8 μmol/L; Vmax/Km (rate of intracellular transport), pralatrexate = 12.6 Vmax/Km (rate of intracellular transport), methotrexate = 0.9
Mechanism of actionThe 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.
TargetKindPharmacological actionActionsOrganismUniProt ID
Dihydrofolate reductaseProteinyes
inhibitor
HumanP00374 details
Thymidylate synthaseProteinyes
inhibitor
HumanP04818 details
Related Articles
AbsorptionPralatrexate demonstrates linear pharmacokinetics with a multiphasic decline with both diasteromers over dose range of 30-325 mg/m^2. Bioavailability, nonformulated preparation = 13 - 20%
Volume of distribution

Vss, R-pralatrexate = 37 L
Vss, S-pralatrexate = 105 L

Protein binding67 - 86% bound to plasma protein, albumin is the major binder. Does not significantly displace substrates from proteins.
Metabolism

No involvement of CYP450 enzyme system or glucuronidases.

Route of elimination35% of drug is excreted unchanged in the urine (no difference between R- and S- pralatrexate). May be some net renal tubular excretion.
Half life12-18 hours
Clearance

R- pralatrexate = 191 mL/min
S- pralatrexate = 417 mL/min
Mean clearance of both enantiomers is 220 mL/min.

ToxicityMucositis is the dose-limiting toxicity. Folic acid and vitamin B12 supplements do not prevent mucositis from happening.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug Interactions
DrugInteractionDrug group
AceclofenacThe serum concentration of Pralatrexate can be increased when it is combined with Aceclofenac.Approved
AcetovanilloneThe serum concentration of Pralatrexate can be increased when it is combined with Acetovanillone.Investigational
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Pralatrexate.Approved
Acetylsalicylic acidThe serum concentration of Pralatrexate can be increased when it is combined with Acetylsalicylic acid.Approved, Vet Approved
AdapaleneThe serum concentration of Pralatrexate can be increased when it is combined with Adapalene.Approved
ALT-110The risk or severity of adverse effects can be increased when Pralatrexate is combined with ALT-110.Investigational
Aminosalicylic AcidThe serum concentration of Pralatrexate can be increased when it is combined with Aminosalicylic Acid.Approved
AnisodamineThe serum concentration of Pralatrexate can be increased when it is combined with Anisodamine.Investigational
AntipyrineThe serum concentration of Pralatrexate can be increased when it is combined with Antipyrine.Approved
AnvirzelAnvirzel may decrease the cardiotoxic activities of Pralatrexate.Investigational
ApremilastThe serum concentration of Pralatrexate can be increased when it is combined with Apremilast.Approved, Investigational
AzapropazoneThe serum concentration of Pralatrexate can be increased when it is combined with Azapropazone.Withdrawn
AzelastineThe serum concentration of Pralatrexate can be increased when it is combined with Azelastine.Approved
BalsalazideThe serum concentration of Pralatrexate can be increased when it is combined with Balsalazide.Approved, Investigational
BcgThe therapeutic efficacy of Bcg can be decreased when used in combination with Pralatrexate.Investigational
BenoxaprofenThe serum concentration of Pralatrexate can be increased when it is combined with Benoxaprofen.Withdrawn
Betulinic AcidThe serum concentration of Pralatrexate can be increased when it is combined with Betulinic Acid.Investigational
BevacizumabBevacizumab may increase the cardiotoxic activities of Pralatrexate.Approved, Investigational
BromfenacThe serum concentration of Pralatrexate can be increased when it is combined with Bromfenac.Approved
BucillamineThe serum concentration of Pralatrexate can be increased when it is combined with Bucillamine.Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Pralatrexate.Approved
CarprofenThe serum concentration of Pralatrexate can be increased when it is combined with Carprofen.Approved, Vet Approved, Withdrawn
CastanospermineThe serum concentration of Pralatrexate can be increased when it is combined with Castanospermine.Experimental
CDX-110The risk or severity of adverse effects can be increased when Pralatrexate is combined with CDX-110.Investigational
CelecoxibThe serum concentration of Pralatrexate can be increased when it is combined with Celecoxib.Approved, Investigational
ChloroquineThe serum concentration of Pralatrexate can be increased when it is combined with Chloroquine.Approved, Vet Approved
ClonixinThe serum concentration of Pralatrexate can be increased when it is combined with Clonixin.Approved
CurcuminThe serum concentration of Pralatrexate can be increased when it is combined with Curcumin.Investigational
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Pralatrexate.Approved, Investigational
D-LimoneneThe serum concentration of Pralatrexate can be increased when it is combined with D-Limonene.Investigational
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Pralatrexate.Approved
dersalazineThe serum concentration of Pralatrexate can be increased when it is combined with dersalazine.Investigational
DeslanosideDeslanoside may decrease the cardiotoxic activities of Pralatrexate.Approved
DiclofenacThe serum concentration of Pralatrexate can be increased when it is combined with Diclofenac.Approved, Vet Approved
DiflunisalThe serum concentration of Pralatrexate can be increased when it is combined with Diflunisal.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Pralatrexate.Approved
DigoxinDigoxin may decrease the cardiotoxic activities of Pralatrexate.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Pralatrexate.Approved, Investigational
DroxicamThe serum concentration of Pralatrexate can be increased when it is combined with Droxicam.Approved
DuvelisibThe serum concentration of Pralatrexate can be increased when it is combined with Duvelisib.Investigational
E6201The serum concentration of Pralatrexate can be increased when it is combined with E6201.Investigational
EbselenThe serum concentration of Pralatrexate can be increased when it is combined with Ebselen.Investigational
EpirizoleThe serum concentration of Pralatrexate can be increased when it is combined with Epirizole.Approved
EtanerceptThe serum concentration of Pralatrexate can be increased when it is combined with Etanercept.Approved, Investigational
EtodolacThe serum concentration of Pralatrexate can be increased when it is combined with Etodolac.Approved, Investigational, Vet Approved
EtofenamateThe serum concentration of Pralatrexate can be increased when it is combined with Etofenamate.Approved
EtoricoxibThe serum concentration of Pralatrexate can be increased when it is combined with Etoricoxib.Approved, Investigational
Evening primrose oilThe serum concentration of Pralatrexate can be increased when it is combined with Evening primrose oil.Approved
exisulindThe serum concentration of Pralatrexate can be increased when it is combined with exisulind.Investigational
FenbufenThe serum concentration of Pralatrexate can be increased when it is combined with Fenbufen.Approved
FenoprofenThe serum concentration of Pralatrexate can be increased when it is combined with Fenoprofen.Approved
FingolimodPralatrexate may increase the immunosuppressive activities of Fingolimod.Approved, Investigational
FloctafenineThe serum concentration of Pralatrexate can be increased when it is combined with Floctafenine.Approved, Withdrawn
FlunixinThe serum concentration of Pralatrexate can be increased when it is combined with Flunixin.Vet Approved
FlurbiprofenThe serum concentration of Pralatrexate can be increased when it is combined with Flurbiprofen.Approved, Investigational
G17DTThe risk or severity of adverse effects can be increased when Pralatrexate is combined with G17DT.Investigational
GI-5005The risk or severity of adverse effects can be increased when Pralatrexate is combined with GI-5005.Investigational
HigenamineThe serum concentration of Pralatrexate can be increased when it is combined with Higenamine.Investigational
HMPL-004The serum concentration of Pralatrexate can be increased when it is combined with HMPL-004.Investigational
IbuprofenThe serum concentration of Pralatrexate can be increased when it is combined with Ibuprofen.Approved
IbuproxamThe serum concentration of Pralatrexate can be increased when it is combined with Ibuproxam.Withdrawn
IcatibantThe serum concentration of Pralatrexate can be increased when it is combined with Icatibant.Approved
IndomethacinThe serum concentration of Pralatrexate can be increased when it is combined with Indomethacin.Approved, Investigational
IndoprofenThe serum concentration of Pralatrexate can be increased when it is combined with Indoprofen.Withdrawn
INGN 201The risk or severity of adverse effects can be increased when Pralatrexate is combined with INGN 201.Investigational
INGN 225The risk or severity of adverse effects can be increased when Pralatrexate is combined with INGN 225.Investigational
IsoxicamThe serum concentration of Pralatrexate can be increased when it is combined with Isoxicam.Withdrawn
KebuzoneThe serum concentration of Pralatrexate can be increased when it is combined with Kebuzone.Experimental
KetoprofenThe serum concentration of Pralatrexate can be increased when it is combined with Ketoprofen.Approved, Vet Approved
KetorolacThe serum concentration of Pralatrexate can be increased when it is combined with Ketorolac.Approved
LeflunomideThe risk or severity of adverse effects can be increased when Pralatrexate is combined with Leflunomide.Approved, Investigational
LisofyllineThe serum concentration of Pralatrexate can be increased when it is combined with Lisofylline.Investigational
LornoxicamThe serum concentration of Pralatrexate can be increased when it is combined with Lornoxicam.Approved
LoxoprofenThe serum concentration of Pralatrexate can be increased when it is combined with Loxoprofen.Approved
LumiracoxibThe serum concentration of Pralatrexate can be increased when it is combined with Lumiracoxib.Approved, Investigational
Magnesium salicylateThe serum concentration of Pralatrexate can be increased when it is combined with Magnesium salicylate.Approved
MasoprocolThe serum concentration of Pralatrexate can be increased when it is combined with Masoprocol.Approved
Meclofenamic acidThe serum concentration of Pralatrexate can be increased when it is combined with Meclofenamic acid.Approved, Vet Approved
Mefenamic acidThe serum concentration of Pralatrexate can be increased when it is combined with Mefenamic acid.Approved
MeloxicamThe serum concentration of Pralatrexate can be increased when it is combined with Meloxicam.Approved, Vet Approved
MesalazineThe serum concentration of Pralatrexate can be increased when it is combined with Mesalazine.Approved
MetamizoleThe serum concentration of Pralatrexate can be increased when it is combined with Metamizole.Withdrawn
MizoribineThe serum concentration of Pralatrexate can be increased when it is combined with Mizoribine.Investigational
Mycophenolate mofetilThe serum concentration of Pralatrexate can be increased when it is combined with Mycophenolate mofetil.Approved, Investigational
Mycophenolic acidThe serum concentration of Pralatrexate can be increased when it is combined with Mycophenolic acid.Approved
NabumetoneThe serum concentration of Pralatrexate can be increased when it is combined with Nabumetone.Approved
NafamostatThe serum concentration of Pralatrexate can be increased when it is combined with Nafamostat.Investigational
NaftifineThe serum concentration of Pralatrexate can be increased when it is combined with Naftifine.Approved
NaproxenThe serum concentration of Pralatrexate can be increased when it is combined with Naproxen.Approved, Vet Approved
NatalizumabThe risk or severity of adverse effects can be increased when Pralatrexate is combined with Natalizumab.Approved, Investigational
NCX 4016The serum concentration of Pralatrexate can be increased when it is combined with NCX 4016.Investigational
NepafenacThe serum concentration of Pralatrexate can be increased when it is combined with Nepafenac.Approved
Niflumic AcidThe serum concentration of Pralatrexate can be increased when it is combined with Niflumic Acid.Approved
NimesulideThe serum concentration of Pralatrexate can be increased when it is combined with Nimesulide.Approved, Withdrawn
NitroaspirinThe serum concentration of Pralatrexate can be increased when it is combined with Nitroaspirin.Investigational
OlopatadineThe serum concentration of Pralatrexate can be increased when it is combined with Olopatadine.Approved
OlsalazineThe serum concentration of Pralatrexate can be increased when it is combined with Olsalazine.Approved
OrgoteinThe serum concentration of Pralatrexate can be increased when it is combined with Orgotein.Vet Approved
OuabainOuabain may decrease the cardiotoxic activities of Pralatrexate.Approved
OxaprozinThe serum concentration of Pralatrexate can be increased when it is combined with Oxaprozin.Approved
OxyphenbutazoneThe serum concentration of Pralatrexate can be increased when it is combined with Oxyphenbutazone.Withdrawn
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Pralatrexate.Approved, Vet Approved
ParecoxibThe serum concentration of Pralatrexate can be increased when it is combined with Parecoxib.Approved
PhenylbutazoneThe serum concentration of Pralatrexate can be increased when it is combined with Phenylbutazone.Approved, Vet Approved
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Pralatrexate.Approved, Investigational
PirfenidoneThe serum concentration of Pralatrexate can be increased when it is combined with Pirfenidone.Investigational
PiroxicamThe serum concentration of Pralatrexate can be increased when it is combined with Piroxicam.Approved, Investigational
ProbenecidThe serum concentration of Pralatrexate can be increased when it is combined with Probenecid.Approved
PropacetamolThe serum concentration of Pralatrexate can be increased when it is combined with Propacetamol.Approved
PTC299The serum concentration of Pralatrexate can be increased when it is combined with PTC299.Investigational
Rabies vaccineThe risk or severity of adverse effects can be increased when Pralatrexate is combined with Rabies vaccine.Approved
Rabies vaccineThe therapeutic efficacy of Rabies vaccine can be decreased when used in combination with Pralatrexate.Approved
ResveratrolThe serum concentration of Pralatrexate can be increased when it is combined with Resveratrol.Experimental, Investigational
RofecoxibThe serum concentration of Pralatrexate can be increased when it is combined with Rofecoxib.Investigational, Withdrawn
RoflumilastRoflumilast may increase the immunosuppressive activities of Pralatrexate.Approved
SalicylamideThe serum concentration of Pralatrexate can be increased when it is combined with Salicylamide.Approved
Salicylic acidThe serum concentration of Pralatrexate can be increased when it is combined with Salicylic acid.Approved, Vet Approved
SalsalateThe serum concentration of Pralatrexate can be increased when it is combined with Salsalate.Approved
SapropterinThe serum concentration of Sapropterin can be decreased when it is combined with Pralatrexate.Approved, Investigational
SeratrodastThe serum concentration of Pralatrexate can be increased when it is combined with Seratrodast.Approved, Investigational
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Pralatrexate.Approved
SRP 299The risk or severity of adverse effects can be increased when Pralatrexate is combined with SRP 299.Investigational
SRT501The serum concentration of Pralatrexate can be increased when it is combined with SRT501.Investigational
SulfamethoxazoleThe serum concentration of Pralatrexate can be increased when it is combined with Sulfamethoxazole.Approved
SulfasalazineThe serum concentration of Pralatrexate can be increased when it is combined with Sulfasalazine.Approved
SulindacThe serum concentration of Pralatrexate can be increased when it is combined with Sulindac.Approved
SuprofenThe serum concentration of Pralatrexate can be increased when it is combined with Suprofen.Approved, Withdrawn
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Pralatrexate.Approved, Investigational
TenoxicamThe serum concentration of Pralatrexate can be increased when it is combined with Tenoxicam.Approved
TepoxalinThe serum concentration of Pralatrexate can be increased when it is combined with Tepoxalin.Vet Approved
TeriflunomideThe serum concentration of Pralatrexate can be increased when it is combined with Teriflunomide.Approved
TG4010The risk or severity of adverse effects can be increased when Pralatrexate is combined with TG4010.Investigational
Tiaprofenic acidThe serum concentration of Pralatrexate can be increased when it is combined with Tiaprofenic acid.Approved
TinoridineThe serum concentration of Pralatrexate can be increased when it is combined with Tinoridine.Investigational
TofacitinibPralatrexate may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
Tolfenamic AcidThe serum concentration of Pralatrexate can be increased when it is combined with Tolfenamic Acid.Approved
TolmetinThe serum concentration of Pralatrexate can be increased when it is combined with Tolmetin.Approved
TranilastThe serum concentration of Pralatrexate can be increased when it is combined with Tranilast.Approved, Investigational
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Pralatrexate.Approved, Investigational
TrimethoprimThe serum concentration of Pralatrexate can be increased when it is combined with Trimethoprim.Approved, Vet Approved
Trisalicylate-cholineThe serum concentration of Pralatrexate can be increased when it is combined with Trisalicylate-choline.Approved
ValdecoxibThe serum concentration of Pralatrexate can be increased when it is combined with Valdecoxib.Investigational, Withdrawn
ZaltoprofenThe serum concentration of Pralatrexate can be increased when it is combined with Zaltoprofen.Approved
ZileutonThe serum concentration of Pralatrexate can be increased when it is combined with Zileuton.Approved, Investigational, Withdrawn
ZomepiracThe serum concentration of Pralatrexate can be increased when it is combined with Zomepirac.Withdrawn
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
General References
  1. 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:23409799 ]
  2. 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:22921318 ]
  3. 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:23032692 ]
External Links
ATC CodesL01BA05
AHFS Codes
  • 10:00
PDB EntriesNot Available
FDA labelDownload (266 KB)
MSDSDownload (479 KB)
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.6139
Blood Brain Barrier+0.5561
Caco-2 permeable-0.7518
P-glycoprotein substrateSubstrate0.5845
P-glycoprotein inhibitor INon-inhibitor0.9224
P-glycoprotein inhibitor IINon-inhibitor0.9921
Renal organic cation transporterNon-inhibitor0.938
CYP450 2C9 substrateNon-substrate0.8589
CYP450 2D6 substrateNon-substrate0.8269
CYP450 3A4 substrateNon-substrate0.6396
CYP450 1A2 substrateNon-inhibitor0.8654
CYP450 2C9 inhibitorNon-inhibitor0.8965
CYP450 2D6 inhibitorNon-inhibitor0.9073
CYP450 2C19 inhibitorNon-inhibitor0.9178
CYP450 3A4 inhibitorNon-inhibitor0.6523
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.934
Ames testNon AMES toxic0.8727
CarcinogenicityNon-carcinogens0.9543
BiodegradationNot ready biodegradable0.9493
Rat acute toxicity2.6263 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9803
hERG inhibition (predictor II)Non-inhibitor0.8735
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
InjectionIntravenous20 mg/mL
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6028071 No2002-07-162022-07-16Us
US7622470 No2005-05-312025-05-31Us
US8299078 No2005-05-312025-05-31Us
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0178 mg/mLALOGPS
logP0.1ALOGPS
logP0.33ChemAxon
logS-4.4ALOGPS
pKa (Strongest Acidic)3.44ChemAxon
pKa (Strongest Basic)2.86ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count11ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area207.3 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity126.82 m3·mol-1ChemAxon
Polarizability47.31 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as hippuric acids. These are compounds containing hippuric acid, which consists of a of a benzoyl group linked to the N-terminal of a glycine.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzamides
Direct ParentHippuric acids
Alternative Parents
Substituents
  • N-acyl-alpha amino acid or derivatives
  • N-acyl-alpha-amino acid
  • Hippuric acid
  • Pteridine
  • Monoterpenoid
  • Bicyclic monoterpenoid
  • Aromatic monoterpenoid
  • P-cymene
  • Alpha-amino acid or derivatives
  • N-substituted-alpha-amino acid
  • Benzoic acid or derivatives
  • Benzoyl
  • Aminopyrimidine
  • Amino fatty acid
  • Fatty acyl
  • Imidolactam
  • Pyrimidine
  • Pyrazine
  • Primary aromatic amine
  • Dicarboxylic acid or derivatives
  • Heteroaromatic compound
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Nadph binding
Specific Function:
Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its own mRNA and that of DHFRL1.
Gene Name:
DHFR
Uniprot ID:
P00374
Molecular Weight:
21452.61 Da
References
  1. 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:23409799 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Thymidylate synthase activity
Specific Function:
Contributes to the de novo mitochondrial thymidylate biosynthesis pathway.
Gene Name:
TYMS
Uniprot ID:
P04818
Molecular Weight:
35715.65 Da
References
  1. 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:23409799 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Tetrahydrofolylpolyglutamate synthase activity
Specific Function:
Catalyzes conversion of folates to polyglutamate derivatives allowing concentration of folate compounds in the cell and the intracellular retention of these cofactors, which are important substrates for most of the folate-dependent enzymes that are involved in one-carbon transfer reactions involved in purine, pyrimidine and amino acid synthesis. Unsubstituted reduced folates are the preferred s...
Gene Name:
FPGS
Uniprot ID:
Q05932
Molecular Weight:
64608.53 Da
References
  1. 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:23409799 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Reduced folate carrier activity
Specific Function:
Transporter for the intake of folate. Uptake of folate in human placental choriocarcinoma cells occurs by a novel mechanism called potocytosis which functionally couples three components, namely the folate receptor, the folate transporter, and a V-type H(+)-pump.
Gene Name:
SLC19A1
Uniprot ID:
P41440
Molecular Weight:
64867.62 Da
References
  1. 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:22921318 ]
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Drug created on September 14, 2010 10:21 / Updated on December 07, 2016 02:39