Identification

Summary

Pralatrexate is an antineoplastic agent used for the treatment of relapsed or refractory peripheral T-cell lymphoma.

Brand Names
Folotyn
Generic Name
Pralatrexate
DrugBank Accession Number
DB06813
Background

Pralatrexate is an antifolate for the treatment of relapsed or refractory peripheral T-cell lymphoma 12. Pralatrexate was developed in response due to the inferior responses of patients using the standard therapy for their B-cells counterparts.10 Compared to methotrexate, pralatrexate has better accumulation in cancer cells.10 Pralatrexate is designed to have a higher affinity for the reduced folate carrier, a protein that is overexpressed in malignant cells and is upregulated by oncogenes.11 As such, pralatrexate is thought to have a better therapeutic window compared to other antifolate analogs due to the novel target of RFC.11

Pralatrexate was approved by the FDA on September 24, 2009.12 It is also being studied for other types of lymphoma and solid malignancy such as non-small-cell lung cancer, breast cancer, and bladder cancer.9

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 477.4726
Monoisotopic: 477.176066881
Chemical Formula
C23H23N7O5
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
  • Pralatrexate
  • Pralatrexato
  • Pralatrexatum

Pharmacology

Indication

Pralatrexate is indicated for the treatment of relapsed or refractory peripheral T-cell lymphoma.12

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Associated Conditions
Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug events
Improve clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events & improve clinical decision support.
Learn more
Pharmacodynamics

Pralatrexate is a folate analog that inhibits folate metabolism, thus impeding the synthesis of amino acids and nucleic acid.9 Additionally, pralatrexate also competes for enzymatic processing by folyopolyglutamate synthase (FPGS)with folate to increase cellular retention.9 Compared to methotrexate, pralatrexate binds to the reduced folate carrier protein-1 (RFC-1) for cellular uptake with 10-times the affinity and is a more potent substrate for FPGS.10 The Km value for RFC-1 was calculated to be 0.3 μmol/L and 4.8 μmol/L for pralatrexate and methotrexate respectively, while the Km value for FPGS was estimated to be 5.9 and 32.3 µmol/l for pralatrexate and methotrexate respectively10. As a result, pralatrexate is more cytotoxic and better retained in cancer cells.10

Due to its anti-folate activity, pralatrexate's main toxicity is manifested as mucositis that can require dose interruption or reduction10,13. In 5 patients with non-small-cell lung carcinoma receiving a supratherapeutic dose of 230 mg/m2, the mean change from pre-injection QTcF interval at the end of infusion was 6.1 ms (90%CI: -0.6, 12.7), and at 1-hour post-injection was 7.8 ms (90%CI: 3.0, 12.6).13 However, no patient exceeded a QTcF of 470 msec and exhibited an absolute increase from baseline in QTcF exceeding 30 msec.13 As well, the study dose far exceeded the target dose for patients with peripheral T-cell lymphoma and pralatrexate does not inhibit the human ether-a-go-go-related gene (hERG) K+ channel13. Therefore, pralatrexate uses are unlikely to cause cardiac repolarization delays.9,13.

Mechanism of action

Pralatrexate is a folate analog metabolic inhibitor that competitively inhibits dihydrofolate reductase (DHFR) selectively in cancer cells overexpressing the reduced folate carrier protein-1 (RFC-1).12 Folate is a water-soluble vitamin required for DNA synthesis and maintenance as well as DNA, RNA, and protein methylation. As cancer cells are rapidly replicating, they require a lot of folates to accommodate an accelerated cell division and DNA and protein modification for cellular transformation.5,6 Therefore, interruption with folate metabolism can inhibit tumor growth.12

Additionally, pralatrexate also undergoes polyglutamylation catalyzed by folyopolyglutamate synthase (FPGS).12 This reaction both increases cellular retention of pralatrexate for extended drug action and impedes the uptake of folate, also a substrate of FPGS, to further inhibit folate metabolism in cancer cells.8

TargetActionsOrganism
ADihydrofolate reductase
substrate
inhibitor
Humans
UThymidylate synthase
substrate
inhibitor
Humans
AFolylpolyglutamate synthase, mitochondrial
substrate
Humans
Absorption

With an intravenous formulation, pralatrexate has complete bioavailability.3 Pralatrexate demonstrates a dose-proportional and linear pharmacokinetics over a dose range of 30-325 mg/m2.9 Upon an intravenous push over 3 to 5 minutes of a starting dose of 30 mg/m2 racemic pralatrexate for dose 1 of cycle 1, Cmax and AUC0-∞ was estimated to be 5,815 ng/mL and 267,854 ng/mL.min respectively using a noncomparmental pharmacokinetics analysis.13,9Both pralatrexate diastereomers demonstrates a multiphase decline in plasma concentration with a rapid initial fall followed by a slow terminal phase.9 The initial fall is thought to reflect the clearance of pralatrexate by renal and non-renal mechanism , while the slow terminal phase likely represents the return of pralatrexate from deep intracellular compartments, enterohepatic circulation, or after deglutamination.9

Volume of distribution

The steady-state volume of distribution of pralatrexate S- and R-diastereomers is 105 L and 37 L, respectively.12,3

Protein binding

The protein binding of pralatrexate is approximately 67% in vitro. 12

Metabolism

While the liver has been shown to metabolize pralatrexate to some extent, pralatrexate is not significantly metabolized by any CYP450 isozymes or glucuronidases in vitro.12

Route of elimination

Following a single dose of FOLOTYN 30 mg/m2, approximately 34% of the pralatrexate dose was excreted unchanged into urine. Following a radiolabeled pralatrexate dose, 39% (CV = 28%) of the dose was recovered in urine as unchanged pralatrexate and 34% (CV = 88%) in feces as unchanged pralatrexate and/or any metabolites. 10% (CV = 95%) of the dose was exhaled over 24 hours.12

Half-life

The terminal elimination half-life of pralatrexate was 12-18 hours (coefficient of variance [CV] = 62-120%).12

Clearance

The total systemic clearance of pralatrexate diastereomers was 417 mL/min (S-diastereomer) and 191 mL/min (R-diastereomer).12

Adverse Effects
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.
Learn more
Improve decision support & research outcomes with our structured adverse effects data.
Learn more
Toxicity

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

No specific information is available on the treatment of overdosage of pralatrexate. If an overdose occurs, general supportive measures should be instituted as deemed necessary by the treating healthcare provider. Based on pralatrexate's mechanism of action, consider the prompt administration of leucovorin.12

Carcinogenicity studies and fertility studies have not been performed with pralatrexate.12Based on findings from animal studies and its mechanism of action [see Clinical Pharmacology (12.1)], pralatrexate can cause fetal harm when administered to a pregnant woman. There are insufficient data on pralatrexate use in pregnant women to evaluate for a drug-associated risk. Pralatrexate was embryotoxic and fetotoxic in rats and rabbits when administered during organogenesis at doses about 1.2% (0.012 times) of the clinical dose on an mg/m2 basis. Advise pregnant women of the potential risk to a fetus.12

Pralatrexate did not cause mutations in the Ames test or the Chinese hamster ovary cell chromosome aberration assay. Nevertheless, these tests do not reliably predict genotoxicity for this class of compounds. Pralatrexate did not cause mutations in the mouse micronucleus assay.12

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirAbacavir may decrease the excretion rate of Pralatrexate which could result in a higher serum level.
AbataceptThe risk or severity of adverse effects can be increased when Abatacept is combined with Pralatrexate.
AbemaciclibAbemaciclib may decrease the excretion rate of Pralatrexate which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Pralatrexate which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Pralatrexate which could result in a higher serum level.
AcetaminophenAcetaminophen may decrease the excretion rate of Pralatrexate which could result in a higher serum level.
AcetazolamideThe therapeutic efficacy of Pralatrexate can be increased when used in combination with Acetazolamide.
Acetylsalicylic acidThe serum concentration of Pralatrexate can be increased when it is combined with Acetylsalicylic acid.
AclidiniumPralatrexate may decrease the excretion rate of Aclidinium which could result in a higher serum level.
AcrivastinePralatrexate may decrease the excretion rate of Acrivastine which could result in a higher serum level.
Identify potential medication risks
Easily compare up to 40 drugs with our drug interaction checker.
Get severity rating, description, and management advice.
Learn more
Food Interactions
No interactions found.

Products

Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
FolotynInjection20 mg/1mLIntravenousAcrotech Biopharma Llc2009-09-24Not applicableUS flag
FolotynSolution40 mg / 2 mLIntravenousServierNot applicableNot applicableCanada flag
FolotynInjection40 mg/2mLIntravenousAcrotech Biopharma Inc2009-09-24Not applicableUS flag
FolotynInjection20 mg/1mLIntravenousAcrotech Biopharma Inc2009-09-24Not applicableUS flag
FolotynSolution20 mg / mLIntravenousServier2019-01-15Not applicableCanada flag

Categories

ATC Codes
L01BA05 — Pralatrexate
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
Acetylide / Amine / Amino acid / Aminopyrimidine / Aromatic heteropolycyclic compound / Aromatic monoterpenoid / Azacycle / Benzamide / Benzenoid / Benzoic acid or derivatives
show 29 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
terminal acetylenic compound, N-acyl-L-glutamic acid, pteridines (CHEBI:71223)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
A8Q8I19Q20
CAS number
146464-95-1
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

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. [Article]
  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. [Article]
  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. [Article]
  4. Horwitz SM, Kim YH, Foss F, Zain JM, Myskowski PL, Lechowicz MJ, Fisher DC, Shustov AR, Bartlett NL, Delioukina ML, Koutsoukos T, Saunders ME, O'Connor OA, Duvic M: Identification of an active, well-tolerated dose of pralatrexate in patients with relapsed or refractory cutaneous T-cell lymphoma. Blood. 2012 May 3;119(18):4115-22. doi: 10.1182/blood-2011-11-390211. Epub 2012 Mar 6. [Article]
  5. Crider KS, Yang TP, Berry RJ, Bailey LB: Folate and DNA methylation: a review of molecular mechanisms and the evidence for folate's role. Adv Nutr. 2012 Jan;3(1):21-38. doi: 10.3945/an.111.000992. Epub 2012 Jan 5. [Article]
  6. Kim YI: Role of folate in colon cancer development and progression. J Nutr. 2003 Nov;133(11 Suppl 1):3731S-3739S. doi: 10.1093/jn/133.11.3731S. [Article]
  7. Nunez MI, Behrens C, Woods DM, Lin H, Suraokar M, Kadara H, Hofstetter W, Kalhor N, Lee JJ, Franklin W, Stewart DJ, Wistuba II: High expression of folate receptor alpha in lung cancer correlates with adenocarcinoma histology and EGFR [corrected] mutation. J Thorac Oncol. 2012 May;7(5):833-40. doi: 10.1097/JTO.0b013e31824de09c. [Article]
  8. Assaraf YG: Molecular basis of antifolate resistance. Cancer Metastasis Rev. 2007 Mar;26(1):153-81. [Article]
  9. Foss FM: Evaluation of the pharmacokinetics, preclinical and clinical efficacy of pralatrexate for the treatment of T-cell lymphoma. Expert Opin Drug Metab Toxicol. 2011 Sep;7(9):1141-52. doi: 10.1517/17425255.2011.595404. Epub 2011 Jul 5. [Article]
  10. Marchi E, O'Connor OA: Safety and efficacy of pralatrexate in the treatment of patients with relapsed or refractory peripheral T-cell lymphoma. Ther Adv Hematol. 2012 Aug;3(4):227-35. doi: 10.1177/2040620712445330. [Article]
  11. Mould DR, Sweeney K, Duffull SB, Neylon E, Hamlin P, Horwitz S, Sirotnak F, Fleisher M, Saunders ME, O'Connor OA: A population pharmacokinetic and pharmacodynamic evaluation of pralatrexate in patients with relapsed or refractory non-Hodgkin's or Hodgkin's lymphoma. Clin Pharmacol Ther. 2009 Aug;86(2):190-6. doi: 10.1038/clpt.2009.80. Epub 2009 May 27. [Article]
  12. FDA Approved Drug Products: FOLOTYN (pralatrexate injection) injection [Link]
  13. Health Canada Approved Drug Products: FOLOTYN (pralatrexate injection) injection [Link]
  14. Cayman Chemical: Pralatrexate MSDS [Link]
KEGG Drug
D05589
PubChem Compound
148121
PubChem Substance
175427094
ChemSpider
130578
BindingDB
50457437
RxNav
662019
ChEBI
71223
ChEMBL
CHEMBL1201746
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Pralatrexate
FDA label
Download (266 KB)
MSDS
Download (479 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4RecruitingTreatmentPeripheral T Cell Lymphoma (PTCL) / Progression, Disease1
3CompletedTreatmentCutaneous T-Cell Lymphoma Recurrent / Refractory Peripheral T-cell Lymphoma Unspecified1
3CompletedTreatmentRefractory Peripheral T-cell Lymphoma Unspecified / Relapsed Peripheral T-Cell Lymphoma1
3TerminatedTreatmentPeripheral T Cell Lymphoma (PTCL)1
3WithdrawnOtherPeripheral T Cell Lymphoma (PTCL)1
2CompletedPreventionRefractory Peripheral T-cell Lymphoma Unspecified / Relapsed Peripheral T-Cell Lymphoma1
2CompletedTreatmentAdenocarcinoma of the Oesophagus / Adenocarcinomas of the Gastroesophageal Junction / Esophageal Cancer, Stage IV / Recurrent Esophageal Cancer / Squamous Cell Carcinoma of the Esophagus1
2CompletedTreatmentAdenocarcinoma of the Stomach / Adenocarcinomas of the Gastroesophageal Junction / Advanced Gastric Cancer / Esophageal Undifferentiated Carcinoma / Gastric Squamous Cell Carcinoma / Recurrent Gastric Carcinoma / Recurrent Oesophageal Adenocarcinoma / Recurrent Oesophageal squamous cell 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 / Undifferentiated Gastric Carcinoma1
2CompletedTreatmentAdult T-Cell Leukemia/Lymphoma (ATLL)1
2CompletedTreatmentAnaplastic Large Cell Lymphoma / Angioimmunoblastic T-cell Lymphoma (AITL) / Hepato-splenic T-cell Lymphoma / Peripheral T Cell Lymphoma (PTCL)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
SolutionIntravenous20 mg
InjectionIntravenous20 mg/1mL
InjectionIntravenous40 mg/2mL
SolutionIntravenous20 mg / mL
SolutionIntravenous40 mg / 2 mL
Injection, solutionIntravenous20 mg/1ml
Injection, solutionIntravenous
SolutionIntravenous20 mg/ml
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US6028071No2000-02-222022-07-16US flag
US7622470No2009-11-242025-05-31US flag
US8299078No2012-10-302025-05-31US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
pKa3.25, 4.76, and 6.17https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/022468s014lbl.pdf
Predicted Properties
PropertyValueSource
Water Solubility0.0178 mg/mLALOGPS
logP0.1ALOGPS
logP0.62Chemaxon
logS-4.4ALOGPS
pKa (Strongest Acidic)3.28Chemaxon
pKa (Strongest Basic)2.03Chemaxon
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

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Substrate
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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
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. FDA Approved Drug Products: FOLOTYN (pralatrexate injection) injection [Link]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Foss FM: Evaluation of the pharmacokinetics, preclinical and clinical efficacy of pralatrexate for the treatment of T-cell lymphoma. Expert Opin Drug Metab Toxicol. 2011 Sep;7(9):1141-52. doi: 10.1517/17425255.2011.595404. Epub 2011 Jul 5. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
No
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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
General Function
Organic anion transmembrane transporter activity
Specific Function
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name
ABCC2
Uniprot ID
Q92887
Uniprot Name
Canalicular multispecific organic anion transporter 1
Molecular Weight
174205.64 Da
References
  1. FDA Approved Drug Products: FOLOTYN (pralatrexate injection) injection [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
References
  1. FDA Approved Drug Products: FOLOTYN (pralatrexate injection) injection [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Methotrexate transporter activity
Specific Function
Has been shown to act both as an intestinal proton-coupled high-affinity folate transporter and as an intestinal heme transporter which mediates heme uptake from the gut lumen into duodenal epithel...
Gene Name
SLC46A1
Uniprot ID
Q96NT5
Uniprot Name
Proton-coupled folate transporter
Molecular Weight
49770.04 Da
References
  1. Matherly LH, Wilson MR, Hou Z: The major facilitative folate transporters solute carrier 19A1 and solute carrier 46A1: biology and role in antifolate chemotherapy of cancer. Drug Metab Dispos. 2014 Apr;42(4):632-49. doi: 10.1124/dmd.113.055723. Epub 2014 Jan 6. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
General Function
Organic anion transmembrane transporter activity
Specific Function
May act as an inducible transporter in the biliary and intestinal excretion of organic anions. Acts as an alternative route for the export of bile acids and glucuronides from cholestatic hepatocyte...
Gene Name
ABCC3
Uniprot ID
O15438
Uniprot Name
Canalicular multispecific organic anion transporter 2
Molecular Weight
169341.14 Da
References
  1. FDA Approved Drug Products: FOLOTYN (pralatrexate injection) injection [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da
References
  1. FDA Approved Drug Products: FOLOTYN (pralatrexate injection) injection [Link]

Drug created at September 14, 2010 16:21 / Updated at December 04, 2022 18:48