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
Structure for Pralatrexate (DB06813)
- 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
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Cutaneous t-cell lymphoma ••• ••••• Treatment of Refractory peripheral t-cell lymphoma •••••••••••• Treatment of Relapsed peripheral t-cell lymphoma •••••••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- 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
Target Actions Organism ADihydrofolate reductase substrateinhibitorHumans UThymidylate synthase substrateinhibitorHumans AFolylpolyglutamate synthase, mitochondrial substrateHumans - 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
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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 Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Abacavir may decrease the excretion rate of Pralatrexate which could result in a higher serum level. Abatacept The risk or severity of adverse effects can be increased when Abatacept is combined with Pralatrexate. Abemaciclib Abemaciclib may decrease the excretion rate of Pralatrexate which could result in a higher serum level. Aceclofenac Aceclofenac may decrease the excretion rate of Pralatrexate which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Pralatrexate which could result in a higher serum level. - Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Folotyn Injection 40 mg/2mL Intravenous Acrotech Biopharma Inc 2009-09-24 Not applicable US 
Folotyn Injection 20 mg/1mL Intravenous Acrotech Biopharma Inc 2009-09-24 Not applicable US Folotyn Solution 40 mg / 2 mL Intravenous Servier Not applicable Not applicable Canada 
Folotyn Injection 20 mg/1mL Intravenous Acrotech Biopharma Inc 2009-09-24 Not applicable US Folotyn Solution 20 mg / mL Intravenous Servier 2019-01-15 Not applicable Canada - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Pralatrexate Injection 40 mg/2mL Intravenous Fresenius Kabi USA, LLC 2022-11-15 Not applicable US Pralatrexate Injection 20 mg/1mL Intravenous Fresenius Kabi USA, LLC 2022-11-15 Not applicable US
Categories
- ATC Codes
- L01BA05 — Pralatrexate
- Drug Categories
- Antimetabolites
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- BCRP/ABCG2 Substrates
- Drugs that are Mainly Renally Excreted
- Folic Acid Analogues
- Folic Acid Antagonists
- Heterocyclic Compounds, Fused-Ring
- Immunosuppressive Agents
- Narrow Therapeutic Index Drugs
- OATP1B3 substrates
- Pteridines
- Pterins
- 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
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- Assaraf YG: Molecular basis of antifolate resistance. Cancer Metastasis Rev. 2007 Mar;26(1):153-81. [Article]
- 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]
- 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]
- 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]
- FDA Approved Drug Products: FOLOTYN (pralatrexate injection) injection [Link]
- Health Canada Approved Drug Products: FOLOTYN (pralatrexate injection) injection [Link]
- Cayman Chemical: Pralatrexate MSDS [Link]
- External Links
- KEGG Drug
- D05589
- PubChem Compound
- 148121
- PubChem Substance
- 175427094
- ChemSpider
- 130578
- BindingDB
- 50457437
- 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 Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Unknown Status Treatment Peripheral T-Cell Lymphoma (PTCL) / Progression, Disease 1 3 Completed Treatment Cutaneous T-Cell Lymphoma Recurrent / Refractory Peripheral T-Cell Lymphoma 1 3 Completed Treatment Refractory Peripheral T-Cell Lymphoma / Relapsed Peripheral T-Cell Lymphoma 1 3 Recruiting Treatment Peripheral T-Cell Lymphoma (PTCL) 1 3 Terminated Treatment Peripheral T-Cell Lymphoma (PTCL) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Solution Intravenous 20 mg Injection Intravenous 20 mg/1mL Injection Intravenous 40 mg/2mL Solution Intravenous 20 mg / mL Solution Intravenous 40 mg / 2 mL Injection, solution Intravenous 20 mg/1ml Injection, solution Intravenous Solution Intravenous 20 mg/ml - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US6028071 No 2000-02-22 2022-07-16 US US7622470 No 2009-11-24 2025-05-31 US US8299078 No 2012-10-30 2025-05-31 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source pKa 3.25, 4.76, and 6.17 https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/022468s014lbl.pdf - Predicted Properties
Property Value Source Water Solubility 0.0178 mg/mL ALOGPS logP 0.1 ALOGPS logP 0.62 Chemaxon logS -4.4 ALOGPS pKa (Strongest Acidic) 3.28 Chemaxon pKa (Strongest Basic) 2.03 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
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 242.3529133 predictedDarkChem Lite v0.1.0 [M-H]- 202.22888 predictedDeepCCS 1.0 (2019) [M+H]+ 240.8211133 predictedDarkChem Lite v0.1.0 [M+H]+ 204.62447 predictedDeepCCS 1.0 (2019) [M+Na]+ 241.9542133 predictedDarkChem Lite v0.1.0 [M+Na]+ 210.53697 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- SubstrateInhibitor
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- 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. [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
- 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
- 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
- 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
- SubstrateInhibitor
- 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
- 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
- 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
- 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
- SubstrateInhibitor
- 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
- 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
- FDA Approved Drug Products: FOLOTYN (pralatrexate injection) injection [Link]
Drug created at September 14, 2010 16:21 / Updated at December 05, 2023 12:31