Pralatrexate
DRACPC ID DRACPC0026
Active Ingredients Pralatrexate
Description A folate analogue inhibitor of dihydrofolate reductase (DHFR) exhibiting high affinity for reduced folate carrier-1 (RFC-1) with antineoplastic and immunosuppressive activities. Pralatrexate selectively enters cells expressing RFC-1; intracellularly, this agent is highly polyglutamylated and competes for the folate binding site of DHFR, blocking tetrahydrofolate synthesis, which may result in depletion of nucleotide precursors; inhibition of DNA, RNA and protein synthesis; and apoptotic tumor cell death. Efficient intracellular polyglutamylation of pralatrexate results in higher intracellular concentrations compared to non-polyglutamylated pralatrexate, which is more readily effuxed by the MRP (multidrug resistance protein) drug efflux pump. RFC-1, an oncofetal protein expressed at highest levels during embryonic development, may be over-expressed on the cell surfaces of various cancer cell types.
Synonyms (2S)-2-[[4-[(1RS)-1-[(2, 4-Diaminopteridin-6-yl)methyl]but-3-ynyl]benzoyl]amino]pentanedioic Acid; 10-Propargyl-10-Deazaaminopterin; FOLOTYN; Folotyn; N-(4-{1-[(2,4-Diaminopteridin-6-yl)methyl]but-3-yn-1-yl}benzoyl)-L-glutamic Acid; PDX; Pralatrexate
Type Small Molecule
Disease Peripheral T-cell lymphoma
Classification
DHFR inhibitor Amino acid and derivative
Structure Information
Molecular Formula C23H23N7O5
Molecular Weight 477.5
Active Sequence Not available
Sequence Length Not available
Modification Not available
IUPAC Name (2S)-2-[[4-[1-(2,4-diaminopteridin-6-yl)pent-4-yn-2-yl]benzoyl]amino]pentanedioic acid
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
InChI_Key OGSBUKJUDHAQEA-WMCAAGNKSA-N
SMILES O=C(O)[C@@H](NC(C1=CC=C(C(CC#C)CC2=NC3=C(N)N=C(N)N=C3N=C2)C=C1)=O)CCC(O)=O
External Codes
PubChem CID 148121
DrugBank Accession Number DB06813
NCI Thesaurus Code C2250
UNII A8Q8I19Q20 GSRS
CAS 146464-95-1
Drug approval
Drug indication
Pralatrexate is indicated for the treatment of peripheral T-cell lymphoma (a fast-growing form of non-Hodgkin lymphoma). It is also being studied in the treatment of other types of cancer.
| Drug Name | Strength | Dosage Form/Route | Company | Marketing Status | Drug ID | Approval year |
|---|---|---|---|---|---|---|
| Folotyn | 20mg/ml (20mg/ml) | Solution; Intravenous | Acrotech | Prescription | NDA: 022468 | 2009 |
| Folotyn | 40mg/2ml (20mg/ml) | Solution; Intravenous | Acrotech | Prescription | NDA: 022468 | 2009 |
| Pralatrexate | 20mg/1ml | Injectable;Injection | Teva Pharms Usa Inc | Prescription | ANDA: 206167 | 2016 |
| Pralatrexate | 40mg/2ml | Injectable;Injection | Teva Pharms Usa Inc | Prescription | ANDA: 206167 | 2016 |
| Folotyn | 20 mg / ml | Solution; Intravenous | Servier Canada Inc | Prescription | DIN: 02481820 | 2019 |
| Folotyn | 40 mg / 2 ml | Solution; Intravenous | Servier Canada Inc | Prescription | DIN: 02481855 | 2018 |
| ClinicalTrials.gov Identifier | Title | Condition or disease | Phase | Purpose |
|---|---|---|---|---|
| NCT02594267 | A Phase 1, Dose-Finding Study of Folotyn® (Pralatrexate Injection) Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP) in Patients With Peripheral T-Cell Lymphoma (PTCL) | Peripheral T-Cell Lymphoma (PTCL) | Phase 1 | Treatment |
| NCT00554827 | A Phase 1, Open-label Study of Pralatrexate With Vitamin B12 and Folic Acid Supplementation in Patients With Relapsed or Refractory Cutaneous T-cell Lymphoma | Cutaneous T-cell Lymphoma | Phase 1 | Treatment |
| NCT01532011 | A Phase I Dose-Escalation Study of Erlotinib in Combination With Pralatrexate in Subjects With Advanced Cancer | Advanced Cancers; Solid Tumors | Phase 1 | Treatment |
| NCT01183065 | A Multi-Institution Phase II Study of Pralatrexate With Vitamin B12 and Folic Acid Supplementation for Previously Treated Recurrent or Metastatic Head and Neck Squamous Cell Cancer (HNSCC) | Head and Neck Cancer | Phase 2 | Treatment |
| NCT00606502 | A Randomized, Phase 2b, Multi-center Study of Pralatrexate Versus Erlotinib in Patients With Stage IIIB/IV Non-small Cell Lung Cancer After Failure of at Least 1 Prior Platinum-based Treatment | Non-small Cell Lung Cancer | Phase 2 | Treatment |
More clinical information is obtained from ClinicalTrials.gov.
