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

Structure

 

Show IUPAC/InChI/SMILES

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.





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