Pralatrexate
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Also known as FolotynNSC-754230PDXPralatrexatoSID144206459PRALATREXATE(FOLOTYN)
Summary
Pralatrexate (CHEMBL1201746) is an approved small-molecule antineoplastic agent (ATC L01BA05) targeting DHFR; indicated across 19 conditions including peripheral t-cell lymphoma, not otherwise specified and neoplasm.
At a glance
- Status: Approved (max clinical phase 4)
- Modality: Small molecule
- ATC class: L01BA05
- Targets: 1 (DHFR)
- Indications: 19 conditions
- Clinical trials: 41
- Chemistry: 477.5 Da · C23H23N7O5
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL1201746 |
| Name | Pralatrexate |
| Type | Small molecule |
| Max phase | 4 |
| FDA approved | yes |
| PubChem CID | 148121 |
| ChEBI | CHEBI:71223 |
| ATC | L01BA05 |
| Molecular formula | C23H23N7O5 |
| Molecular weight | 477.5 |
| InChIKey | OGSBUKJUDHAQEA-WMCAAGNKSA-N |
SMILES: C#CCC(CC1=CN=C2C(=N1)C(=NC(=N2)N)N)C3=CC=C(C=C3)C(=O)N[C@@H](CCC(=O)O)C(=O)O
IUPAC name: (2S)-2-[[4-[1-(2,4-diaminopteridin-6-yl)pent-4-yn-2-yl]benzoyl]amino]pentanedioic acid
ChEBI definition: A pteridine that is the N-4-[1-(2,4-diaminopteridin-6-yl)pent-4-yn-2-yl]benzoyl derivative of L-glutamic acid. Used for treatment of Peripheral T-Cell Lymphoma, an aggressive form of non-Hodgkins lymphoma.
Pharmacological roles (ChEBI): antineoplastic agent, EC 1.5.1.3 (dihydrofolate reductase) inhibitor.
Other ChEBI roles (chemical / environmental): antimetabolite.
Also known as: Folotyn, NSC-754230, PDX, Pralatrexate, Pralatrexato, PRALATREXATE, SID144206459, PRALATREXATE(FOLOTYN), Pralatrexate(Folotyn)
Patent coverage: 4,361 distinct patent families (14,348 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 12,343 (86%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.
Targets
Targets
Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).
| Gene | Target | Action | pAffinity | Cancer dependency | UniProt |
|---|---|---|---|---|---|
| DHFR | dihydrofolate reductase | Inhibition | 7.35 | 69.8% | P00374 |
Broader ChEMBL bioactivity targets: 5 (assay-derived). Sample: Proton-coupled folate transporter, Bifunctional dihydrofolate reductase-thymidylate synthase, Dihydrofolate reductase, Folate receptor alpha, Reduced folate transporter.
Bioactivity
ChEMBL activities: 5 potent at pChembl ≥ 5 of 5 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):
| Target | pChembl | Type | Value | Unit | Activity ID |
|---|---|---|---|---|---|
| DHFR | 10.87 | Ki | 0.01 | nM | CHEMBL_ACT_24862079 |
| P13922 | 10.87 | Ki | 0.01 | nM | CHEMBL_ACT_26191709 |
| SLC19A1 | 9.16 | IC50 | 0.69 | nM | CHEMBL_ACT_18527733 |
| SLC46A1 | 7.24 | IC50 | 57 | nM | CHEMBL_ACT_18527799 |
| FOLR1 | 6.78 | IC50 | 168 | nM | CHEMBL_ACT_18527755 |
Target pathways
Aggregated over 1 target gene(s): DHFR.
Top Reactome pathways
3 total, by targets touching each:
| Pathway | Targets | Genes |
|---|---|---|
| Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation | 1 | DHFR |
| Metabolism of folate and pterines | 1 | DHFR |
| G1/S-Specific Transcription | 1 | DHFR |
Dominant GO biological processes
| GO term | Targets |
|---|---|
| tetrahydrobiopterin biosynthetic process | 1 |
| one-carbon metabolic process | 1 |
| negative regulation of translation | 1 |
| axon regeneration | 1 |
| response to methotrexate | 1 |
| dihydrofolate metabolic process | 1 |
| tetrahydrofolate metabolic process | 1 |
| tetrahydrofolate biosynthetic process | 1 |
| folic acid metabolic process | 1 |
| regulation of removal of superoxide radicals | 1 |
Indications & clinical
Indications
19 indications (5 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).
| Indication | Trial phase | MONDO | EFO |
|---|---|---|---|
| peripheral T-cell lymphoma, not otherwise specified | 4 | MONDO:0004964 | EFO:0000211 |
| neoplasm | 4 | MONDO:0005070 | EFO:0000616 |
| mature T-cell and NK-cell non-Hodgkin lymphoma | 4 | MONDO:0000430 | MONDO:0000430 |
| T-cell non-Hodgkin lymphoma | 4 | MONDO:0015760 | MONDO:0015760 |
| lymphoma | 3 | MONDO:0005062 | EFO:0000574 |
| non-small cell lung carcinoma | 2 | MONDO:0005233 | EFO:0003060 |
| head and neck cancer | 2 | MONDO:0005627 | EFO:0006859 |
| breast carcinoma | 2 | MONDO:0004989 | EFO:0000305 |
| lung neoplasm | 2 | MONDO:0021117 | MONDO:0008903 |
| plasma cell myeloma | 1 | MONDO:0009693 | EFO:0001378 |
| primary cutaneous T-cell non-Hodgkin lymphoma | 1 | MONDO:0000607 | EFO:0002913 |
| anaplastic large cell lymphoma | 1 | MONDO:0020325 | EFO:0003032 |
| Sezary syndrome | 1 | MONDO:0017844 | EFO:1000785 |
| mycosis fungoides | 1 | MONDO:0009691 | EFO:1001051 |
| peritoneal neoplasm | 1 | MONDO:0006901 | MONDO:0002087 |
| fallopian tube neoplasm | 1 | MONDO:0021092 | MONDO:0002158 |
| ovarian cancer | 1 | MONDO:0008170 | MONDO:0008170 |
2 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.
Clinical trials
Total trials: 41.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE2 | 12 |
| PHASE1 | 11 |
| PHASE1/PHASE2 | 8 |
| PHASE3 | 7 |
| Not specified | 2 |
| PHASE4 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT03150602 | PHASE4 | UNKNOWN | A Pralatrexate Study in Asian Patients With Peripheral T-cell Lymphoma After Prior Therapy |
| NCT06072131 | PHASE3 | RECRUITING | To Evaluate Efficacy of Belinostat or Pralatrexate in Combination Against CHOP Alone in PTCL |
| NCT06561048 | PHASE3 | RECRUITING | Soquelitinib vs Standard of Care in Participants With Relapsed/Refractory Peripheral T-cell Lymphoma Not Otherwise Specified, Follicular Helper T-cell Lymphomas, or Systemic Anaplastic Large-cell Lymphoma |
| NCT07234162 | PHASE3 | RECRUITING | A Phase 3 Multinational Study of Golidocitinib Versus Investigator’s Choice in r/r PTCL (JACKPOT19) |
| NCT01420679 | PHASE3 | TERMINATED | Pralatrexate vs Observation Following CHOP-based Chemotherapy in Undiagnosed Peripheral T-cell Lymphoma Patients |
| NCT01482962 | PHASE3 | COMPLETED | Alisertib (MLN8237) or Investigator’s Choice in Patients With Relapsed/Refractory Peripheral T-Cell Lymphoma |
| NCT03349333 | PHASE3 | COMPLETED | A Single Arm Study Evaluating the Efficacy and Safety of Pralatrexate in Subjects With Relapsed or Refractory PTCL |
| NCT03355768 | PHASE3 | WITHDRAWN | Romidepsin Versus Combination of Romidepsin Plus Pralatrexate in PTCL |
| NCT03161223 | PHASE1/PHASE2 | RECRUITING | Durvalumab in Different Combinations With Pralatrexate, Romidepsin and Oral 5-Azacitidine for Lymphoma |
| NCT03598998 | PHASE1/PHASE2 | ACTIVE_NOT_RECRUITING | Pembrolizumab and Pralatrexate in Treating Patients With Relapsed or Refractory Peripheral T-Cell Lymphomas |
| NCT04747236 | PHASE2 | RECRUITING | Randomized Phase IIB Trial of Oral Azacytidine Plus Romidepsin Versus Investigator’s Choice in PTCL |
| NCT07225985 | PHASE1/PHASE2 | RECRUITING | Pralatrexate With Bendamustine and Total-Body Irradiation Followed by Donor Stem Cell Transplant for the Treatment of Relapsed or Refractory T-Cell Non-Hodgkin Lymphoma |
| NCT00004238 | PHASE2 | COMPLETED | 10-Propargyl-10-Deazaaminopterin in Treating Patients With Stage IIIB or Stage IV Non-small Cell Lung Cancer |
| NCT00052442 | PHASE1/PHASE2 | COMPLETED | 10-Propargyl-10-Deazaaminopterin in Treating Patients With Recurrent or Refractory Non-Hodgkin’s Lymphoma or Hodgkin’s Lymphoma |
| NCT00364923 | PHASE2 | COMPLETED | Study of Pralatrexate With Vitamin B12 and Folic Acid in Patients With Relapsed or Refractory Peripheral T-cell Lymphoma |
| NCT00481871 | PHASE1/PHASE2 | COMPLETED | Study of Pralatrexate & Gemcitabine With B12 & Folic Acid to Treat Relapsed/Refractory Lymphoproliferative Malignancies |
| NCT00606502 | PHASE2 | COMPLETED | Study of Pralatrexate vs. Erlotinib for Non-Small Cell Lung Cancer After at Least 1 Prior Platinum-based Treatment |
| NCT00722553 | PHASE2 | COMPLETED | Study of Pralatrexate to Treat Advanced or Metastatic Relapsed Transitional Cell Carcinoma of the Urinary Bladder |
| NCT00998946 | PHASE2 | COMPLETED | Study of Pralatrexate to Treat Participants With Relapsed or Refractory B-cell Non-Hodgkin’s Lymphoma |
| NCT01118624 | PHASE2 | COMPLETED | Study of Pralatrexate in Female Patients With Previously-treated Breast Cancer |
| NCT01129206 | PHASE2 | COMPLETED | Pralatrexate and Docetaxel in Treating Patients With Stage IV Esophageal or Gastroesophageal Cancer Who Have Failed Platinum-Based Therapy |
| NCT01178944 | PHASE2 | COMPLETED | Pralatrexate and Oxaliplatin in Treating Patients With Unresectable or Metastatic Esophageal, Stomach, or Gastroesophageal Junction Cancer |
| NCT01188876 | PHASE1/PHASE2 | COMPLETED | Carboplatin/Pralatrexate in Recurrent Platinum-Sensitive Ovarian, Fallopian or Primary Peritoneal Cancer |
| NCT01336933 | PHASE2 | COMPLETED | Combination Chemotherapy and Pralatrexate as First-Line Therapy in Treating Patients With Non-Hodgkin Lymphoma |
| NCT01626664 | PHASE2 | COMPLETED | KW-0761 or Investigator’s Choice in Subjects With Previously Treated Adult T-cell Leukemia-Lymphoma (ATL) |
| NCT01947140 | PHASE1/PHASE2 | COMPLETED | Pralatrexate + Romidepsin in Relapsed/Refractory Lymphoid Malignancies |
| NCT02013362 | PHASE1/PHASE2 | COMPLETED | Phase I/II Clinical Study of Pralatrexate in Japanese Patients With Relapsed or Refractory Peripheral T-cell Lymphoma |
| NCT02106650 | PHASE2 | COMPLETED | Phase II Study of Folotyn With Leucovorin to Prevent/Reduce Mucositis in Patients With Hematological Malignancies |
| NCT03240211 | PHASE1 | ACTIVE_NOT_RECRUITING | Study of Pembrolizumab Combined With Decitabine and Pralatrexate in PTCL and CTCL |
| NCT07036133 | PHASE1 | RECRUITING | Study to Evaluate the Pharmacokinetics and Safety of Pralatrexate in Patients With Advanced Solid Tumor or Hematological Malignancy and Either Normal Hepatic Function or Mild, Moderate, or Severe Hepatic Impairment |
| NCT00024245 | PHASE1 | COMPLETED | 10-Propargyl-10-Deazaaminopterin Plus Probenecid in Treating Patients With Advanced Solid Tumors |
| NCT00554827 | PHASE1 | COMPLETED | Study of Pralatrexate in Patients With Relapsed or Refractory Cutaneous T-cell Lymphoma |
| NCT01114282 | PHASE1 | COMPLETED | Phase I Bortezomib (VELCADE) in Combo With Pralatrexate in Relapsed/Refractory MM |
| NCT01134341 | PHASE1 | COMPLETED | Pralatrexate and Bexarotene in Patients With Relapsed or Refractory Cutaneous T-cell Lymphoma |
| NCT01206465 | PHASE1 | COMPLETED | Pralatrexate and Fluorouracil in Treating Patients With Recurrent Solid Tumors |
| NCT01532011 | PHASE1 | COMPLETED | Erlotinib in Combination With Pralatrexate in Advanced Malignancies |
| NCT01789723 | PHASE1 | WITHDRAWN | Phase 1 Study of Fusilev to Prevent or Reduce Mucositis in Patients With Non-Hodgkin’s Lymphoma Receiving Folotyn |
| NCT01820091 | PHASE1 | WITHDRAWN | Phase 1 Study of Fusilev® to Prevent or Reduce Mucositis in Patients With Non-Small Cell Lung Cancer Receiving Folotyn® |
| NCT02594267 | PHASE1 | COMPLETED | A Dose-Finding Study of Folotyn® (Pralatrexate Injection) Plus CHOP With Peripheral T-Cell Lymphoma (PTCL) |
| NCT03356678 | Not specified | COMPLETED | Pralatrexate for Relapsed or Refractory Peripheral T-cell Lymphoma |
Clinical evidence (CIViC)
No CIViC predictive evidence (expected for non-precision-medicine drugs).
Pharmacology
Pharmacogenomics
No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.
Related molecules
Related molecules
Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.
22 molecules share ≥1 primary target. Top 22 by shared-target count:
| Molecule | Source | Status | Shared targets |
|---|---|---|---|
| LEUCOVORIN | ChEMBL + PubChem | Phase 4 (approved) | DHFR |
| METHOTREXATE | ChEMBL + PubChem | Phase 4 (approved) | DHFR |
| PEMETREXED | ChEMBL + PubChem | Phase 4 (approved) | DHFR |
| DIFLUNISAL | ChEMBL | Phase 4 (approved) | DHFR |
| GENTAMICIN | ChEMBL | Phase 4 (approved) | DHFR |
| MEFENAMIC ACID | ChEMBL | Phase 4 (approved) | DHFR |
| PYRIMETHAMINE | ChEMBL | Phase 4 (approved) | DHFR |
| RALTITREXED | ChEMBL | Phase 4 (approved) | DHFR |
| SULFACETAMIDE | ChEMBL | Phase 4 (approved) | DHFR |
| SULFADIAZINE | ChEMBL | Phase 4 (approved) | DHFR |
| TERIFLUNOMIDE | ChEMBL | Phase 4 (approved) | DHFR |
| TRIMETHOPRIM | ChEMBL | Phase 4 (approved) | DHFR |
| TRIMETREXATE | ChEMBL | Phase 4 (approved) | DHFR |
| ICLAPRIM | ChEMBL | Phase 3 | DHFR |
| AMINOPTERIN | ChEMBL | Phase 2 | DHFR |
| BREQUINAR | ChEMBL | Phase 2 | DHFR |
| CYCLOGUANIL | ChEMBL | Phase 2 | DHFR |
| DIAVERIDINE | ChEMBL | Phase 2 | DHFR |
| EDATREXATE | ChEMBL | Phase 2 | DHFR |
| EPIROPRIM | ChEMBL | Phase 2 | DHFR |
| PIRITREXIM | ChEMBL | Phase 2 | DHFR |
| Folic Acid | PubChem | Approved | DHFR |
Related Atlas pages
- Genes: DHFR
- Diseases: peripheral T-cell lymphoma, not otherwise specified, neoplasm, mature T-cell and NK-cell non-Hodgkin lymphoma, T-cell non-Hodgkin lymphoma, lymphoma
- Drugs: Methotrexate, Pemetrexed, Diflunisal, Gentamicin, Mefenamic Acid, Pyrimethamine, Raltitrexed, Sulfacetamide, Sulfadiazine, Teriflunomide, Trimethoprim, Trimetrexate, Iclaprim, Folic Acid