Identification

Name
Pralatrexate
Accession Number
DB06813  (DB05527)
Type
Small Molecule
Groups
Approved
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.

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
  • N-(4-(1-((2,4-Diamino-6-pteridinyl)methyl)-3-butynyl)benzoyl)-L-glutamic acid
  • PDX
  • Pralatrexato
  • Pralatrexatum
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
FolotynInjection20 mg/mLIntravenousAllos Therapeutics2009-09-24Not applicableUs
Categories
UNII
A8Q8I19Q20
CAS number
146464-95-1
Weight
Average: 477.4726
Monoisotopic: 477.176066881
Chemical Formula
C23H23N7O5
InChI Key
OGSBUKJUDHAQEA-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[[email protected]@H](CCC(O)=O)C(O)=O)N=C2C(N)=N1

Pharmacology

Indication

Treatment of relapsed or refractory peripheral T-cell lymphoma.

Structured Indications
Pharmacodynamics

Pralatrexate 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 action

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.

TargetActionsOrganism
ADihydrofolate reductase
inhibitor
Human
AThymidylate synthase
inhibitor
Human
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%

Volume of distribution

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

Protein binding

67 - 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 elimination

35% of drug is excreted unchanged in the urine (no difference between R- and S- pralatrexate). May be some net renal tubular excretion.

Half life

12-18 hours

Clearance

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

Toxicity

Mucositis is the dose-limiting toxicity. Folic acid and vitamin B12 supplements do not prevent mucositis from happening.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AceclofenacThe serum concentration of Pralatrexate can be increased when it is combined with Aceclofenac.Approved, Investigational
AcemetacinThe serum concentration of Pralatrexate can be increased when it is combined with Acemetacin.Approved
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Pralatrexate.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Pralatrexate.Experimental
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
AlclofenacThe serum concentration of Pralatrexate can be increased when it is combined with Alclofenac.Approved, Withdrawn
AlminoprofenThe serum concentration of Pralatrexate can be increased when it is combined with Alminoprofen.Experimental
AloxiprinThe serum concentration of Pralatrexate can be increased when it is combined with Aloxiprin.Experimental
Aminosalicylic AcidThe serum concentration of Pralatrexate can be increased when it is combined with Aminosalicylic Acid.Approved
AndrographolideThe serum concentration of Pralatrexate can be increased when it is combined with Andrographolide.Investigational
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
ApocyninThe serum concentration of Pralatrexate can be increased when it is combined with Apocynin.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
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Pralatrexate.Investigational
BendazacThe serum concentration of Pralatrexate can be increased when it is combined with Bendazac.Experimental
BenorilateThe serum concentration of Pralatrexate can be increased when it is combined with Benorilate.Experimental
BenoxaprofenThe serum concentration of Pralatrexate can be increased when it is combined with Benoxaprofen.Withdrawn
BenzydamineThe serum concentration of Pralatrexate can be increased when it is combined with Benzydamine.Approved
BevacizumabBevacizumab may increase the cardiotoxic activities of Pralatrexate.Approved, Investigational
BevoniumThe serum concentration of Pralatrexate can be increased when it is combined with Bevonium.Experimental
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
BufexamacThe serum concentration of Pralatrexate can be increased when it is combined with Bufexamac.Experimental
BumadizoneThe serum concentration of Pralatrexate can be increased when it is combined with Bumadizone.Experimental
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
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
Choline magnesium trisalicylateThe serum concentration of Pralatrexate can be increased when it is combined with Choline magnesium trisalicylate.Approved
ClonixinThe serum concentration of Pralatrexate can be increased when it is combined with Clonixin.Approved
Clostridium tetani toxoid antigen (formaldehyde inactivated)The therapeutic efficacy of Clostridium tetani toxoid antigen (formaldehyde inactivated) can be decreased when used in combination with Pralatrexate.Approved
Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated)The therapeutic efficacy of Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated) can be decreased when used in combination with Pralatrexate.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
CymarinCymarin may decrease the cardiotoxic activities of Pralatrexate.Experimental
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
DifenpiramideThe serum concentration of Pralatrexate can be increased when it is combined with Difenpiramide.Experimental
DiflunisalThe serum concentration of Pralatrexate can be increased when it is combined with Diflunisal.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Pralatrexate.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of Pralatrexate.Approved
Digoxin Immune Fab (Ovine)Digoxin Immune Fab (Ovine) 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
E-6201The serum concentration of Pralatrexate can be increased when it is combined with E-6201.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
EthenzamideThe serum concentration of Pralatrexate can be increased when it is combined with Ethenzamide.Experimental
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, Investigational
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, Investigational
exisulindThe serum concentration of Pralatrexate can be increased when it is combined with exisulind.Investigational
FelbinacThe serum concentration of Pralatrexate can be increased when it is combined with Felbinac.Experimental
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
FentiazacThe serum concentration of Pralatrexate can be increased when it is combined with Fentiazac.Experimental
FeprazoneThe serum concentration of Pralatrexate can be increased when it is combined with Feprazone.Experimental
Ferulic acidThe serum concentration of Pralatrexate can be increased when it is combined with Ferulic acid.Experimental
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
FlunoxaprofenThe serum concentration of Pralatrexate can be increased when it is combined with Flunoxaprofen.Experimental
FlurbiprofenThe serum concentration of Pralatrexate can be increased when it is combined with Flurbiprofen.Approved, Investigational
G17DTThe therapeutic efficacy of G17DT can be decreased when used in combination with Pralatrexate.Investigational
GI-5005The therapeutic efficacy of GI-5005 can be decreased when used in combination with Pralatrexate.Investigational
GitoformateGitoformate may decrease the cardiotoxic activities of Pralatrexate.Experimental
GuacetisalThe serum concentration of Pralatrexate can be increased when it is combined with Guacetisal.Experimental
Hemoglobin crosfumarilThe serum concentration of Pralatrexate can be increased when it is combined with Hemoglobin crosfumaril.Experimental
Hepatitis A VaccineThe therapeutic efficacy of Hepatitis A Vaccine can be decreased when used in combination with Pralatrexate.Approved
Hepatitis B Vaccine (Recombinant)The therapeutic efficacy of Hepatitis B Vaccine (Recombinant) can be decreased when used in combination with Pralatrexate.Approved, Withdrawn
HigenamineThe serum concentration of Pralatrexate can be increased when it is combined with Higenamine.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
Imidazole salicylateThe serum concentration of Pralatrexate can be increased when it is combined with Imidazole salicylate.Experimental
IndobufenThe serum concentration of Pralatrexate can be increased when it is combined with Indobufen.Investigational
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 therapeutic efficacy of INGN 201 can be decreased when used in combination with Pralatrexate.Investigational
INGN 225The therapeutic efficacy of INGN 225 can be decreased when used in combination with Pralatrexate.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
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Pralatrexate.Experimental
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
LonazolacThe serum concentration of Pralatrexate can be increased when it is combined with Lonazolac.Experimental
LornoxicamThe serum concentration of Pralatrexate can be increased when it is combined with Lornoxicam.Approved, Investigational
LoxoprofenThe serum concentration of Pralatrexate can be increased when it is combined with Loxoprofen.Approved, Investigational
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, Investigational
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.Investigational, Withdrawn
Methyl salicylateThe serum concentration of Pralatrexate can be increased when it is combined with Methyl salicylate.Approved, Vet Approved
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Pralatrexate.Experimental
MizoribineThe serum concentration of Pralatrexate can be increased when it is combined with Mizoribine.Investigational
MofebutazoneThe serum concentration of Pralatrexate can be increased when it is combined with Mofebutazone.Experimental
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.Approved, 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
NepafenacThe serum concentration of Pralatrexate can be increased when it is combined with Nepafenac.Approved
NifenazoneThe serum concentration of Pralatrexate can be increased when it is combined with Nifenazone.Experimental
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, Investigational, Withdrawn
NitroaspirinThe serum concentration of Pralatrexate can be increased when it is combined with Nitroaspirin.Investigational
OleandrinOleandrin may decrease the cardiotoxic activities of Pralatrexate.Experimental, 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.Approved, 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
ParthenolideThe serum concentration of Pralatrexate can be increased when it is combined with Parthenolide.Investigational
PeruvosidePeruvoside may decrease the cardiotoxic activities of Pralatrexate.Experimental
PhenylbutazoneThe serum concentration of Pralatrexate can be increased when it is combined with Phenylbutazone.Approved, Vet Approved
PimecrolimusThe serum concentration of Pralatrexate can be increased when it is combined with Pimecrolimus.Approved, Investigational
PirfenidoneThe serum concentration of Pralatrexate can be increased when it is combined with Pirfenidone.Approved, Investigational
PiroxicamThe serum concentration of Pralatrexate can be increased when it is combined with Piroxicam.Approved, Investigational
PirprofenThe serum concentration of Pralatrexate can be increased when it is combined with Pirprofen.Experimental
PranoprofenThe serum concentration of Pralatrexate can be increased when it is combined with Pranoprofen.Experimental, Investigational
ProbenecidThe serum concentration of Pralatrexate can be increased when it is combined with Probenecid.Approved
ProglumetacinThe serum concentration of Pralatrexate can be increased when it is combined with Proglumetacin.Experimental
PropacetamolThe serum concentration of Pralatrexate can be increased when it is combined with Propacetamol.Approved, Investigational
PropyphenazoneThe serum concentration of Pralatrexate can be increased when it is combined with Propyphenazone.Experimental
ProquazoneThe serum concentration of Pralatrexate can be increased when it is combined with Proquazone.Experimental
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Pralatrexate.Experimental
PTC299The serum concentration of Pralatrexate can be increased when it is combined with PTC299.Investigational
Rabies virus inactivated antigen, AThe risk or severity of adverse effects can be increased when Pralatrexate is combined with Rabies virus inactivated antigen, A.Approved
Rabies virus inactivated antigen, AThe therapeutic efficacy of Rabies virus inactivated antigen, A can be decreased when used in combination with Pralatrexate.Approved
ResveratrolThe serum concentration of Pralatrexate can be increased when it is combined with Resveratrol.Approved, Experimental, Investigational
RindopepimutThe therapeutic efficacy of Rindopepimut can be decreased when used in combination with Pralatrexate.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
Rotavirus VaccineThe therapeutic efficacy of Rotavirus Vaccine can be decreased when used in combination with Pralatrexate.Approved
Rubella virus vaccineThe therapeutic efficacy of Rubella virus vaccine can be decreased when used in combination with 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
Salmonella typhi ty21a live antigenThe therapeutic efficacy of Salmonella typhi ty21a live antigen can be decreased when used in combination with Pralatrexate.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
SemapimodThe serum concentration of Pralatrexate can be increased when it is combined with Semapimod.Investigational
SeratrodastThe serum concentration of Pralatrexate can be increased when it is combined with Seratrodast.Approved
SerrapeptaseThe serum concentration of Pralatrexate can be increased when it is combined with Serrapeptase.Investigational
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Pralatrexate.Approved
SRP 299The therapeutic efficacy of SRP 299 can be decreased when used in combination with Pralatrexate.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
SuxibuzoneThe serum concentration of Pralatrexate can be increased when it is combined with Suxibuzone.Experimental
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Pralatrexate.Approved, Investigational
TarenflurbilThe serum concentration of Pralatrexate can be increased when it is combined with Tarenflurbil.Investigational
TecemotideThe therapeutic efficacy of Tecemotide can be decreased when used in combination with Pralatrexate.Investigational
TenidapThe serum concentration of Pralatrexate can be increased when it is combined with Tenidap.Experimental
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 therapeutic efficacy of TG4010 can be decreased when used in combination with Pralatrexate.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
TribenosideThe serum concentration of Pralatrexate can be increased when it is combined with Tribenoside.Experimental
TrimethoprimThe serum concentration of Pralatrexate can be increased when it is combined with Trimethoprim.Approved, Vet Approved
TriptolideThe serum concentration of Pralatrexate can be increased when it is combined with Triptolide.Investigational
Trolamine salicylateThe serum concentration of Pralatrexate can be increased when it is combined with Trolamine salicylate.Approved
ValdecoxibThe serum concentration of Pralatrexate can be increased when it is combined with Valdecoxib.Investigational, Withdrawn
Yellow fever vaccineThe therapeutic efficacy of Yellow fever vaccine can be decreased when used in combination with Pralatrexate.Approved
ZaltoprofenThe serum concentration of Pralatrexate can be increased when it is combined with Zaltoprofen.Approved, Investigational
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
Zoster vaccineThe therapeutic efficacy of Zoster vaccine can be decreased when used in combination with Pralatrexate.Approved
Food Interactions
Not Available

References

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
KEGG Drug
D05589
PubChem Compound
148121
PubChem Substance
175427094
ChemSpider
130578
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71223
ChEMBL
CHEMBL1201746
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Wikipedia
Pralatrexate
ATC Codes
L01BA05 — Pralatrexate
FDA label
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MSDS
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Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentAdvanced Cancers / Tumors, Solid1
1CompletedTreatmentCutaneous T-Cell Lymphoma (CTCL)1
1CompletedTreatmentCutaneous T-Cell Lymphoma (CTCL) / Mycosis Fungoides (MF) / Primary Cutaneous Anaplastic Large Cell Lymphoma / Sezary Syndrome1
1CompletedTreatmentMultiple Myeloma (MM)1
1CompletedTreatmentUnspecified Adult Solid Tumor, Protocol Specific1
1RecruitingTreatmentPeripheral T-Cell Lymphoma (PTCL)1
1Unknown StatusTreatmentUnspecified Adult Solid Tumor, Protocol Specific1
1WithdrawnPreventionLung Cancer Non-Small Cell Cancer (NSCLC)1
1WithdrawnPreventionNon Hodgkin Lymphoma (NHL)1
1, 2Active Not RecruitingTreatmentCancer, Ovarian / Fallopian Tube Cancer / Malignant Peritoneal Neoplasm1
1, 2CompletedTreatmentLymphoma, B-Cell / Lymphoma, Hodgkins / Peripheral T-Cell Lymphoma (PTCL) / Relapsed or Refractory Lymphoproliferative Malignancies / Waldenstrom's Macroglobulinemia (WM)1
1, 2CompletedTreatmentPeripheral T-Cell Lymphoma (PTCL)1
1, 2Not Yet RecruitingTreatmentT-Cell Lymphomas1
1, 2RecruitingTreatmentLymphoid Malignancies / Lymphoma, Hodgkins / Malignant Lymphomas / Multiple Myeloma (MM) / Non-Hodgkin's Lymphoma (NHL)1
2Active Not RecruitingTreatmentAdult T-cell lymphomas/leukaemias1
2CompletedTreatmentAdenocarcinoma of the Esophagus / Adenocarcinomas of the Gastroesophageal Junction / Recurrent Esophageal Cancer / Squamous Cell Carcinoma of the Esophagus / Stage IV Esophageal Cancer1
2CompletedTreatmentAdenocarcinomas of the Gastroesophageal Junction / Esophageal Undifferentiated Carcinoma / Gastric Adenocarcinoma / Gastric Squamous Cell Carcinoma / Recurrent Esophageal Adenocarcinoma / Recurrent Esophageal Squamous Cell Carcinoma / Recurrent Gastric Carcinoma / Stage IIIB Esophageal Adenocarcinoma / Stage IIIB Esophageal Squamous Cell Carcinoma / Stage IIIB Gastric Cancer / Stage IIIC Esophageal Adenocarcinoma / Stage IIIC Esophageal Squamous Cell Carcinoma / Stage IIIC Gastric Cancer / Stage IV Esophageal Adenocarcinoma / Stage IV Esophageal Squamous Cell Carcinoma / Stage IV Gastric Cancer / Undifferentiated Gastric Carcinoma1
2CompletedTreatmentBladder Cancers / Neoplasm, Bladder / Transitional Cell Carcinoma1
2CompletedTreatmentCancer of the Breast / Cancer, Breast / Human Mammary Carcinoma / Neoplasms, Breast / Tumors, Breast1
2CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2CompletedTreatmentLung Cancers1
2CompletedTreatmentLymphoma, B-Cell1
2CompletedTreatmentMalignant Lymphomas1
2CompletedTreatmentPeripheral T-Cell Lymphoma (PTCL)1
2RecruitingPreventionPeripheral T-cell lymphoma unspecified refractory / Relapsed Peripheral T-Cell Lymphoma1
2Unknown StatusTreatmentAnaplastic Large Cell Lymphoma / Angioimmunoblastic T-Cell Lymphoma / Hepatosplenic T-Cell Lymphoma / Peripheral T-Cell Lymphoma (PTCL)1
3Active Not RecruitingTreatmentPeripheral T-cell lymphoma unspecified refractory / Relapsed Peripheral T-Cell Lymphoma1
3TerminatedTreatmentPeripheral T-Cell Lymphoma (PTCL)1
4RecruitingTreatmentPeripheral T Cell Lymphoma (PTCL) / Progression, Disease1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
InjectionIntravenous20 mg/mL
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6028071No2002-07-162022-07-16Us
US7622470No2005-05-312025-05-31Us
US8299078No2005-05-312025-05-31Us

Properties

State
Solid
Experimental Properties
Not 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 FiveNoChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-004i-1513900000-5596beb52832aa3566cc

Taxonomy

Description
This compound belongs to the class of organic compounds known as glutamic acid and derivatives. These are compounds containing glutamic acid or a derivative thereof resulting from reaction of glutamic acid at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Glutamic acid and derivatives
Alternative Parents
N-acyl-alpha amino acids / Hippuric acids / Pteridines and derivatives / Aromatic monoterpenoids / Bicyclic monoterpenoids / Benzoyl derivatives / Aminopyrimidines and derivatives / Pyrazines / Imidolactams / Dicarboxylic acids and derivatives
show 11 more
Substituents
Glutamic acid or derivatives / Hippuric acid / N-acyl-alpha-amino acid / N-acyl-alpha amino acid or derivatives / Hippuric acid or derivatives / P-cymene / Aromatic monoterpenoid / Monoterpenoid / Bicyclic monoterpenoid / Pteridine
show 29 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
terminal acetylenic compound, N-acyl-L-glutamic acid, pteridines (CHEBI:71223)

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 pre...
Gene Name
DHFR
Uniprot ID
P00374
Uniprot Name
Dihydrofolate reductase
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
Uniprot Name
Thymidylate synthase
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 substrate...
Gene Name
FPGS
Uniprot ID
Q05932
Uniprot Name
Folylpolyglutamate synthase, mitochondrial
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 th...
Gene Name
SLC19A1
Uniprot ID
P41440
Uniprot Name
Folate transporter 1
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]

Drug created on September 14, 2010 10:21 / Updated on November 09, 2017 03:56