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IdentificationPharmacologyInteractionsReferencesTrialsEconomicsPropertiesSpectraTaxonomyIdentification
- Name
- Pralatrexate
- Accession Number
- DB06813 (DB05527)
- Type
- Small Molecule
- Groups
- Approved, Investigational
- 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
Structure for DB06813 (Pralatrexate)
- 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
Name Dosage Strength Route Labeller Marketing Start Marketing End Folotyn Injection 20 mg/mL Intravenous Allos Therapeutics 2009-09-24 Not applicable US 
- 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[C@@H](CCC(O)=O)C(O)=O)N=C2C(N)=N1
Pharmacology
- Indication
Treatment of relapsed or refractory peripheral T-cell lymphoma.
- Associated Conditions
- 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.Target Actions Organism ADihydrofolate reductase inhibitorHuman AThymidylate synthase inhibitorHuman - 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
Drug Interaction Drug group (4R)-limonene The serum concentration of Pralatrexate can be increased when it is combined with (4R)-limonene. Investigational Aceclofenac The serum concentration of Pralatrexate can be increased when it is combined with Aceclofenac. Approved, Investigational Acemetacin The serum concentration of Pralatrexate can be increased when it is combined with Acemetacin. Approved, Experimental, Investigational Acetyldigitoxin Acetyldigitoxin may decrease the cardiotoxic activities of Pralatrexate. Approved Acetyldigoxin Acetyldigoxin may decrease the cardiotoxic activities of Pralatrexate. Experimental Acetylsalicylic acid The serum concentration of Pralatrexate can be increased when it is combined with Acetylsalicylic acid. Approved, Vet Approved Adapalene The serum concentration of Pralatrexate can be increased when it is combined with Adapalene. Approved Alclofenac The serum concentration of Pralatrexate can be increased when it is combined with Alclofenac. Approved, Withdrawn Alminoprofen The serum concentration of Pralatrexate can be increased when it is combined with Alminoprofen. Experimental Aloxiprin The serum concentration of Pralatrexate can be increased when it is combined with Aloxiprin. Experimental Aminosalicylic Acid The serum concentration of Pralatrexate can be increased when it is combined with Aminosalicylic Acid. Approved Ancestim The risk or severity of cytotoxicity can be increased when Ancestim is combined with Pralatrexate. Approved, Investigational, Withdrawn Andrographolide The serum concentration of Pralatrexate can be increased when it is combined with Andrographolide. Investigational Anisodamine The serum concentration of Pralatrexate can be increased when it is combined with Anisodamine. Investigational Anthrax immune globulin human The risk or severity of adverse effects can be increased when Pralatrexate is combined with Anthrax immune globulin human. Approved Antipyrine The serum concentration of Pralatrexate can be increased when it is combined with Antipyrine. Approved, Investigational Apocynin The serum concentration of Pralatrexate can be increased when it is combined with Apocynin. Investigational Apremilast The serum concentration of Pralatrexate can be increased when it is combined with Apremilast. Approved, Investigational Azapropazone The serum concentration of Pralatrexate can be increased when it is combined with Azapropazone. Withdrawn Azelastine The serum concentration of Pralatrexate can be increased when it is combined with Azelastine. Approved Bacillus calmette-guerin substrain connaught live antigen The risk or severity of adverse effects can be increased when Pralatrexate is combined with Bacillus calmette-guerin substrain connaught live antigen. Approved, Investigational Bacillus calmette-guerin substrain tice live antigen The risk or severity of adverse effects can be increased when Pralatrexate is combined with Bacillus calmette-guerin substrain tice live antigen. Approved Balsalazide The serum concentration of Pralatrexate can be increased when it is combined with Balsalazide. Approved, Investigational BCG vaccine The therapeutic efficacy of BCG vaccine can be decreased when used in combination with Pralatrexate. Investigational Bendazac The serum concentration of Pralatrexate can be increased when it is combined with Bendazac. Experimental Benorilate The serum concentration of Pralatrexate can be increased when it is combined with Benorilate. Experimental Benoxaprofen The serum concentration of Pralatrexate can be increased when it is combined with Benoxaprofen. Withdrawn Benzydamine The serum concentration of Pralatrexate can be increased when it is combined with Benzydamine. Approved Bevacizumab Bevacizumab may increase the cardiotoxic activities of Pralatrexate. Approved, Investigational Bevonium The serum concentration of Pralatrexate can be increased when it is combined with Bevonium. Experimental Bromfenac The serum concentration of Pralatrexate can be increased when it is combined with Bromfenac. Approved Bucillamine The serum concentration of Pralatrexate can be increased when it is combined with Bucillamine. Investigational Bufexamac The serum concentration of Pralatrexate can be increased when it is combined with Bufexamac. Approved, Experimental Bumadizone The serum concentration of Pralatrexate can be increased when it is combined with Bumadizone. Experimental Cabazitaxel The risk or severity of adverse effects can be increased when Cabazitaxel is combined with Pralatrexate. Approved Carbaspirin calcium The serum concentration of Pralatrexate can be increased when it is combined with Carbaspirin calcium. Experimental, Investigational Carprofen The serum concentration of Pralatrexate can be increased when it is combined with Carprofen. Approved, Vet Approved, Withdrawn Castanospermine The serum concentration of Pralatrexate can be increased when it is combined with Castanospermine. Experimental Celecoxib The serum concentration of Pralatrexate can be increased when it is combined with Celecoxib. Approved, Investigational Chloroquine The serum concentration of Pralatrexate can be increased when it is combined with Chloroquine. Approved, Investigational, Vet Approved Choline magnesium trisalicylate The serum concentration of Pralatrexate can be increased when it is combined with Choline magnesium trisalicylate. Approved Clonixin The serum concentration of Pralatrexate can be increased when it is combined with Clonixin. Approved Clostridium tetani toxoid antigen (formaldehyde inactivated) The risk or severity of adverse effects can be increased when Pralatrexate is combined with Clostridium tetani toxoid antigen (formaldehyde inactivated). Approved Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated) The risk or severity of adverse effects can be increased when Pralatrexate is combined with Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated). Approved Curcumin The serum concentration of Pralatrexate can be increased when it is combined with Curcumin. Approved, Investigational Cyclophosphamide Cyclophosphamide may increase the cardiotoxic activities of Pralatrexate. Approved, Investigational Cymarin Cymarin may decrease the cardiotoxic activities of Pralatrexate. Experimental Denosumab The risk or severity of adverse effects can be increased when Denosumab is combined with Pralatrexate. Approved Dersalazine The serum concentration of Pralatrexate can be increased when it is combined with Dersalazine. Investigational Deslanoside Deslanoside may decrease the cardiotoxic activities of Pralatrexate. Approved Diclofenac The serum concentration of Pralatrexate can be increased when it is combined with Diclofenac. Approved, Vet Approved Difenpiramide The serum concentration of Pralatrexate can be increased when it is combined with Difenpiramide. Experimental Diflunisal The serum concentration of Pralatrexate can be increased when it is combined with Diflunisal. Approved, Investigational Digitoxin Digitoxin may decrease the cardiotoxic activities of Pralatrexate. Approved, Investigational Digoxin Digoxin may decrease the cardiotoxic activities of Pralatrexate. Approved Digoxin Immune Fab (Ovine) Digoxin Immune Fab (Ovine) may decrease the cardiotoxic activities of Pralatrexate. Approved Docetaxel The risk or severity of adverse effects can be increased when Docetaxel is combined with Pralatrexate. Approved, Investigational Droxicam The serum concentration of Pralatrexate can be increased when it is combined with Droxicam. Withdrawn Duvelisib The serum concentration of Pralatrexate can be increased when it is combined with Duvelisib. Investigational E-6201 The serum concentration of Pralatrexate can be increased when it is combined with E-6201. Investigational Epirizole The serum concentration of Pralatrexate can be increased when it is combined with Epirizole. Approved Etanercept The serum concentration of Pralatrexate can be increased when it is combined with Etanercept. Approved, Investigational Ethenzamide The serum concentration of Pralatrexate can be increased when it is combined with Ethenzamide. Experimental Etodolac The serum concentration of Pralatrexate can be increased when it is combined with Etodolac. Approved, Investigational, Vet Approved Etofenamate The serum concentration of Pralatrexate can be increased when it is combined with Etofenamate. Approved, Investigational Etoricoxib The serum concentration of Pralatrexate can be increased when it is combined with Etoricoxib. Approved, Investigational Evening primrose oil The serum concentration of Pralatrexate can be increased when it is combined with Evening primrose oil. Investigational, Nutraceutical Exisulind The serum concentration of Pralatrexate can be increased when it is combined with Exisulind. Investigational Felbinac The serum concentration of Pralatrexate can be increased when it is combined with Felbinac. Experimental Fenbufen The serum concentration of Pralatrexate can be increased when it is combined with Fenbufen. Approved Fenoprofen The serum concentration of Pralatrexate can be increased when it is combined with Fenoprofen. Approved Fentiazac The serum concentration of Pralatrexate can be increased when it is combined with Fentiazac. Experimental Feprazone The serum concentration of Pralatrexate can be increased when it is combined with Feprazone. Experimental Ferulic acid The serum concentration of Pralatrexate can be increased when it is combined with Ferulic acid. Experimental Fingolimod Pralatrexate may increase the immunosuppressive activities of Fingolimod. Approved, Investigational Floctafenine The serum concentration of Pralatrexate can be increased when it is combined with Floctafenine. Approved, Withdrawn Flunixin The serum concentration of Pralatrexate can be increased when it is combined with Flunixin. Vet Approved Flunoxaprofen The serum concentration of Pralatrexate can be increased when it is combined with Flunoxaprofen. Experimental Flurbiprofen The serum concentration of Pralatrexate can be increased when it is combined with Flurbiprofen. Approved, Investigational G17DT The risk or severity of adverse effects can be increased when Pralatrexate is combined with G17DT. Investigational GI-5005 The risk or severity of adverse effects can be increased when Pralatrexate is combined with GI-5005. Investigational Gitoformate Gitoformate may decrease the cardiotoxic activities of Pralatrexate. Experimental Guacetisal The serum concentration of Pralatrexate can be increased when it is combined with Guacetisal. Experimental Hemoglobin crosfumaril The serum concentration of Pralatrexate can be increased when it is combined with Hemoglobin crosfumaril. Experimental Hepatitis A Vaccine The risk or severity of adverse effects can be increased when Pralatrexate is combined with Hepatitis A Vaccine. Approved Hepatitis B Vaccine (Recombinant) The risk or severity of adverse effects can be increased when Pralatrexate is combined with Hepatitis B Vaccine (Recombinant). Approved, Withdrawn Higenamine The serum concentration of Pralatrexate can be increased when it is combined with Higenamine. Investigational Human rabies virus immune globulin The risk or severity of adverse effects can be increased when Pralatrexate is combined with Human rabies virus immune globulin. Approved Ibuprofen The serum concentration of Pralatrexate can be increased when it is combined with Ibuprofen. Approved Ibuproxam The serum concentration of Pralatrexate can be increased when it is combined with Ibuproxam. Withdrawn Icatibant The serum concentration of Pralatrexate can be increased when it is combined with Icatibant. Approved, Investigational Imidazole salicylate The serum concentration of Pralatrexate can be increased when it is combined with Imidazole salicylate. Experimental Indobufen The serum concentration of Pralatrexate can be increased when it is combined with Indobufen. Investigational Indomethacin The serum concentration of Pralatrexate can be increased when it is combined with Indomethacin. Approved, Investigational Indoprofen The serum concentration of Pralatrexate can be increased when it is combined with Indoprofen. Withdrawn INGN 201 The risk or severity of adverse effects can be increased when Pralatrexate is combined with INGN 201. Investigational INGN 225 The risk or severity of adverse effects can be increased when Pralatrexate is combined with INGN 225. Investigational Isoxicam The serum concentration of Pralatrexate can be increased when it is combined with Isoxicam. Withdrawn Japanese encephalitis virus strain sa 14-14-2 antigen (formaldehyde inactivated) The risk or severity of adverse effects can be increased when Pralatrexate is combined with Japanese encephalitis virus strain sa 14-14-2 antigen (formaldehyde inactivated). Approved Kebuzone The serum concentration of Pralatrexate can be increased when it is combined with Kebuzone. Experimental Ketoprofen The serum concentration of Pralatrexate can be increased when it is combined with Ketoprofen. Approved, Vet Approved Ketorolac The serum concentration of Pralatrexate can be increased when it is combined with Ketorolac. Approved Lanatoside C Lanatoside C may decrease the cardiotoxic activities of Pralatrexate. Experimental Leflunomide The risk or severity of adverse effects can be increased when Pralatrexate is combined with Leflunomide. Approved, Investigational Lipegfilgrastim Pralatrexate may increase the myelosuppressive activities of Lipegfilgrastim. Approved, Investigational Lisofylline The serum concentration of Pralatrexate can be increased when it is combined with Lisofylline. Investigational Lonazolac The serum concentration of Pralatrexate can be increased when it is combined with Lonazolac. Experimental Lornoxicam The serum concentration of Pralatrexate can be increased when it is combined with Lornoxicam. Approved, Investigational Loxoprofen The serum concentration of Pralatrexate can be increased when it is combined with Loxoprofen. Approved, Investigational Lumiracoxib The serum concentration of Pralatrexate can be increased when it is combined with Lumiracoxib. Approved, Investigational Magnesium salicylate The serum concentration of Pralatrexate can be increased when it is combined with Magnesium salicylate. Approved Masoprocol The serum concentration of Pralatrexate can be increased when it is combined with Masoprocol. Approved, Investigational Meclofenamic acid The serum concentration of Pralatrexate can be increased when it is combined with Meclofenamic acid. Approved, Vet Approved Mefenamic acid The serum concentration of Pralatrexate can be increased when it is combined with Mefenamic acid. Approved Meloxicam The serum concentration of Pralatrexate can be increased when it is combined with Meloxicam. Approved, Vet Approved Mesalazine The serum concentration of Pralatrexate can be increased when it is combined with Mesalazine. Approved Metamizole The serum concentration of Pralatrexate can be increased when it is combined with Metamizole. Approved, Investigational, Withdrawn Methyl salicylate The serum concentration of Pralatrexate can be increased when it is combined with Methyl salicylate. Approved, Vet Approved Metildigoxin Metildigoxin may decrease the cardiotoxic activities of Pralatrexate. Experimental Mizoribine The serum concentration of Pralatrexate can be increased when it is combined with Mizoribine. Investigational Mofebutazone The serum concentration of Pralatrexate can be increased when it is combined with Mofebutazone. Experimental Mycophenolate mofetil The serum concentration of Pralatrexate can be increased when it is combined with Mycophenolate mofetil. Approved, Investigational Mycophenolic acid The serum concentration of Pralatrexate can be increased when it is combined with Mycophenolic acid. Approved Nabumetone The serum concentration of Pralatrexate can be increased when it is combined with Nabumetone. Approved Nafamostat The serum concentration of Pralatrexate can be increased when it is combined with Nafamostat. Approved, Investigational Naftifine The serum concentration of Pralatrexate can be increased when it is combined with Naftifine. Approved Naproxen The serum concentration of Pralatrexate can be increased when it is combined with Naproxen. Approved, Vet Approved Natalizumab The risk or severity of adverse effects can be increased when Pralatrexate is combined with Natalizumab. Approved, Investigational Nepafenac The serum concentration of Pralatrexate can be increased when it is combined with Nepafenac. Approved, Investigational Nifenazone The serum concentration of Pralatrexate can be increased when it is combined with Nifenazone. Experimental Niflumic Acid The serum concentration of Pralatrexate can be increased when it is combined with Niflumic Acid. Approved Nimesulide The serum concentration of Pralatrexate can be increased when it is combined with Nimesulide. Approved, Investigational, Withdrawn Nitroaspirin The serum concentration of Pralatrexate can be increased when it is combined with Nitroaspirin. Investigational Ocrelizumab Ocrelizumab may increase the immunosuppressive activities of Pralatrexate. Approved, Investigational Oleandrin Oleandrin may decrease the cardiotoxic activities of Pralatrexate. Experimental, Investigational Olopatadine The serum concentration of Pralatrexate can be increased when it is combined with Olopatadine. Approved Olsalazine The serum concentration of Pralatrexate can be increased when it is combined with Olsalazine. Approved Orgotein The serum concentration of Pralatrexate can be increased when it is combined with Orgotein. Vet Approved Ouabain Ouabain may decrease the cardiotoxic activities of Pralatrexate. Approved Oxaprozin The serum concentration of Pralatrexate can be increased when it is combined with Oxaprozin. Approved Oxyphenbutazone The serum concentration of Pralatrexate can be increased when it is combined with Oxyphenbutazone. Approved, Withdrawn Paclitaxel The risk or severity of adverse effects can be increased when Paclitaxel is combined with Pralatrexate. Approved, Vet Approved Palmidrol The serum concentration of Pralatrexate can be increased when it is combined with Palmidrol. Experimental, Nutraceutical Parecoxib The serum concentration of Pralatrexate can be increased when it is combined with Parecoxib. Approved Parthenolide The serum concentration of Pralatrexate can be increased when it is combined with Parthenolide. Approved, Investigational Peruvoside Peruvoside may decrease the cardiotoxic activities of Pralatrexate. Experimental Phenyl aminosalicylate The serum concentration of Pralatrexate can be increased when it is combined with Phenyl aminosalicylate. Approved Phenylbutazone The serum concentration of Pralatrexate can be increased when it is combined with Phenylbutazone. Approved, Vet Approved Pimecrolimus The risk or severity of adverse effects can be increased when Pimecrolimus is combined with Pralatrexate. Approved, Investigational Pirfenidone The serum concentration of Pralatrexate can be increased when it is combined with Pirfenidone. Approved, Investigational Piroxicam The serum concentration of Pralatrexate can be increased when it is combined with Piroxicam. Approved, Investigational Pirprofen The serum concentration of Pralatrexate can be increased when it is combined with Pirprofen. Experimental Pranoprofen The serum concentration of Pralatrexate can be increased when it is combined with Pranoprofen. Experimental, Investigational Probenecid The serum concentration of Pralatrexate can be increased when it is combined with Probenecid. Approved, Investigational Proglumetacin The serum concentration of Pralatrexate can be increased when it is combined with Proglumetacin. Experimental Propacetamol The serum concentration of Pralatrexate can be increased when it is combined with Propacetamol. Approved, Investigational Propyphenazone The serum concentration of Pralatrexate can be increased when it is combined with Propyphenazone. Experimental Proquazone The serum concentration of Pralatrexate can be increased when it is combined with Proquazone. Experimental Proscillaridin Proscillaridin may decrease the cardiotoxic activities of Pralatrexate. Experimental PTC299 The serum concentration of Pralatrexate can be increased when it is combined with PTC299. Investigational Rabies virus inactivated antigen, A The risk or severity of adverse effects can be increased when Pralatrexate is combined with Rabies virus inactivated antigen, A. Approved, Investigational Rabies virus inactivated antigen, A The therapeutic efficacy of Rabies virus inactivated antigen, A can be decreased when used in combination with Pralatrexate. Approved, Investigational Resveratrol The serum concentration of Pralatrexate can be increased when it is combined with Resveratrol. Approved, Experimental, Investigational Rindopepimut The risk or severity of adverse effects can be increased when Pralatrexate is combined with Rindopepimut. Investigational Rofecoxib The serum concentration of Pralatrexate can be increased when it is combined with Rofecoxib. Approved, Investigational, Withdrawn Roflumilast Roflumilast may increase the immunosuppressive activities of Pralatrexate. Approved Rotavirus Vaccine The risk or severity of adverse effects can be increased when Pralatrexate is combined with Rotavirus Vaccine. Approved Rubella virus vaccine The risk or severity of adverse effects can be increased when Pralatrexate is combined with Rubella virus vaccine. Approved, Investigational Salicylamide The serum concentration of Pralatrexate can be increased when it is combined with Salicylamide. Approved Salicylic acid The serum concentration of Pralatrexate can be increased when it is combined with Salicylic acid. Approved, Investigational, Vet Approved Salmonella typhi ty2 vi polysaccharide antigen The risk or severity of adverse effects can be increased when Pralatrexate is combined with Salmonella typhi ty2 vi polysaccharide antigen. Approved Salmonella typhi ty21a live antigen The risk or severity of adverse effects can be increased when Pralatrexate is combined with Salmonella typhi ty21a live antigen. Approved Salsalate The serum concentration of Pralatrexate can be increased when it is combined with Salsalate. Approved Sapropterin The serum concentration of Sapropterin can be decreased when it is combined with Pralatrexate. Approved, Investigational Semapimod The serum concentration of Pralatrexate can be increased when it is combined with Semapimod. Investigational Seratrodast The serum concentration of Pralatrexate can be increased when it is combined with Seratrodast. Approved Serrapeptase The serum concentration of Pralatrexate can be increased when it is combined with Serrapeptase. Investigational Sipuleucel-T The therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Pralatrexate. Approved, Investigational SRP 299 The risk or severity of adverse effects can be increased when Pralatrexate is combined with SRP 299. Investigational SRT501 The serum concentration of Pralatrexate can be increased when it is combined with SRT501. Investigational Sulfamethoxazole The serum concentration of Pralatrexate can be increased when it is combined with Sulfamethoxazole. Approved Sulfasalazine The serum concentration of Pralatrexate can be increased when it is combined with Sulfasalazine. Approved Sulindac The serum concentration of Pralatrexate can be increased when it is combined with Sulindac. Approved, Investigational Suprofen The serum concentration of Pralatrexate can be increased when it is combined with Suprofen. Approved, Withdrawn Suxibuzone The serum concentration of Pralatrexate can be increased when it is combined with Suxibuzone. Experimental Tacrolimus Tacrolimus may increase the immunosuppressive activities of Pralatrexate. Approved, Investigational Tarenflurbil The serum concentration of Pralatrexate can be increased when it is combined with Tarenflurbil. Investigational Tecemotide The risk or severity of adverse effects can be increased when Pralatrexate is combined with Tecemotide. Investigational Tenidap The serum concentration of Pralatrexate can be increased when it is combined with Tenidap. Experimental Tenoxicam The serum concentration of Pralatrexate can be increased when it is combined with Tenoxicam. Approved Tepoxalin The serum concentration of Pralatrexate can be increased when it is combined with Tepoxalin. Vet Approved Teriflunomide The serum concentration of Pralatrexate can be increased when it is combined with Teriflunomide. Approved TG4010 The risk or severity of adverse effects can be increased when Pralatrexate is combined with TG4010. Investigational Tiaprofenic acid The serum concentration of Pralatrexate can be increased when it is combined with Tiaprofenic acid. Approved Tinoridine The serum concentration of Pralatrexate can be increased when it is combined with Tinoridine. Investigational Tofacitinib Pralatrexate may increase the immunosuppressive activities of Tofacitinib. Approved, Investigational Tolfenamic Acid The serum concentration of Pralatrexate can be increased when it is combined with Tolfenamic Acid. Approved, Investigational Tolmetin The serum concentration of Pralatrexate can be increased when it is combined with Tolmetin. Approved Tranilast The serum concentration of Pralatrexate can be increased when it is combined with Tranilast. Approved, Investigational Trastuzumab Trastuzumab may increase the cardiotoxic activities of Pralatrexate. Approved, Investigational Tribenoside The serum concentration of Pralatrexate can be increased when it is combined with Tribenoside. Experimental Trimethoprim The serum concentration of Pralatrexate can be increased when it is combined with Trimethoprim. Approved, Vet Approved Triptolide The serum concentration of Pralatrexate can be increased when it is combined with Triptolide. Investigational Trolamine salicylate The serum concentration of Pralatrexate can be increased when it is combined with Trolamine salicylate. Approved Typhoid Vaccine The risk or severity of adverse effects can be increased when Pralatrexate is combined with Typhoid Vaccine. Approved Valdecoxib The serum concentration of Pralatrexate can be increased when it is combined with Valdecoxib. Approved, Investigational, Withdrawn Varicella Zoster Vaccine (Live/Attenuated) The risk or severity of adverse effects can be increased when Pralatrexate is combined with Varicella Zoster Vaccine (Live/Attenuated). Approved Yellow Fever Vaccine The risk or severity of adverse effects can be increased when Pralatrexate is combined with Yellow Fever Vaccine. Approved, Investigational Zaltoprofen The serum concentration of Pralatrexate can be increased when it is combined with Zaltoprofen. Approved, Investigational Zileuton The serum concentration of Pralatrexate can be increased when it is combined with Zileuton. Approved, Investigational, Withdrawn Zomepirac The serum concentration of Pralatrexate can be increased when it is combined with Zomepirac. Withdrawn - Food Interactions
- Not Available
References
- General References
- 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]
- 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]
- 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
- ChEBI
- 71223
- ChEMBL
- CHEMBL1201746
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Pralatrexate
- ATC Codes
- L01BA05 — Pralatrexate
- FDA label
- Download (266 KB)
- MSDS
- Download (479 KB)
Clinical Trials
- Clinical Trials
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage forms
Form Route Strength Injection Intravenous 20 mg/mL - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) US6028071 No 2002-07-16 2022-07-16 US US7622470 No 2005-05-31 2025-05-31 US US8299078 No 2005-05-31 2025-05-31 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0178 mg/mL ALOGPS logP 0.1 ALOGPS logP 0.33 ChemAxon logS -4.4 ALOGPS pKa (Strongest Acidic) 3.44 ChemAxon pKa (Strongest Basic) 2.86 ChemAxon Physiological Charge -2 ChemAxon Hydrogen Acceptor Count 11 ChemAxon Hydrogen Donor Count 5 ChemAxon Polar Surface Area 207.3 Å2 ChemAxon Rotatable Bond Count 10 ChemAxon Refractivity 126.82 m3·mol-1 ChemAxon Polarizability 47.31 Å3 ChemAxon Number of Rings 3 ChemAxon Bioavailability 0 ChemAxon Rule of Five No ChemAxon Ghose Filter Yes ChemAxon Veber's Rule No ChemAxon MDDR-like Rule Yes ChemAxon - Predicted ADMET features
Property Value Probability Human Intestinal Absorption - 0.6139 Blood Brain Barrier + 0.5561 Caco-2 permeable - 0.7518 P-glycoprotein substrate Substrate 0.5845 P-glycoprotein inhibitor I Non-inhibitor 0.9224 P-glycoprotein inhibitor II Non-inhibitor 0.9921 Renal organic cation transporter Non-inhibitor 0.938 CYP450 2C9 substrate Non-substrate 0.8589 CYP450 2D6 substrate Non-substrate 0.8269 CYP450 3A4 substrate Non-substrate 0.6396 CYP450 1A2 substrate Non-inhibitor 0.8654 CYP450 2C9 inhibitor Non-inhibitor 0.8965 CYP450 2D6 inhibitor Non-inhibitor 0.9073 CYP450 2C19 inhibitor Non-inhibitor 0.9178 CYP450 3A4 inhibitor Non-inhibitor 0.6523 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.934 Ames test Non AMES toxic 0.8727 Carcinogenicity Non-carcinogens 0.9543 Biodegradation Not ready biodegradable 0.9493 Rat acute toxicity 2.6263 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9803 hERG inhibition (predictor II) Non-inhibitor 0.8735
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available MS/MS Spectrum - , positive LC-MS/MS splash10-004i-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
- 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
- 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
- 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
- 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 July 02, 2018 18:36