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Pralatrexate DHFR inhibitor

Cat.No.S1497

Pralatrexate is an antifolate, and structurally a folate analog. Its IC50 is < 300 nM in some cell lines. This compound induces tumor cell apoptosis.
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Quality Control

Batch: S149701 DMSO]28 mg/mL]false]Water]Insoluble]false]Ethanol]Insoluble]false Purity: 99.58%
99.58

Cell Culture, Treatment & Working Concentration

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human KB cells Growth inhibition assay 96 h Growth inhibition of human KB cells expressing human RFC/FRalpha/PCFT after 96 hrs by CellTiter-blue assay, IC50=0.47 nM
Chinese hamster R2 cells Growth inhibition assay 96 h Growth inhibition of Chinese hamster R2 cells expressing human PCFT4 after 96 hrs by CellTiter-blue assay, IC50=0.057 μM
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Solubility

In vitro
Batch:

DMSO : 28 mg/mL (58.64 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

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In vivo
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Chemical Information, Storage & Stability

Molecular Weight 477.47 Formula

C23H23N7O5

Storage (From the date of receipt)
CAS No. 146464-95-1 Download SDF Storage of Stock Solutions

Synonyms NSC 754230 SMILES C#CCC(CC1=CN=C2C(=N1)C(=NC(=N2)N)N)C3=CC=C(C=C3)C(=O)NC(CCC(=O)O)C(=O)O

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Mechanism of Action

Targets/IC50/Ki
DHFR
In vitro
Pralatrexate and bortezomib exhibits concentration- and time-dependent cytotoxicity against a broad panel of T-lymphoma cell lines. This compound shows synergism when combined with bortezomib in all cell lines studied. It also induces potent apoptosis and caspase activation when combined with bortezomib across the panel. The agent significantly modulates the expression of p27, NOXA, HH3, and RFC-1 as assessed by Western blot assays. This compound is rationally designed for improved cellular transport via RFC-1, and to have greater intracellular drug retention through the enhanced formation of polyglutamylated conjugates. It is thought to exert its pharmacological effect primarily through inhibition of DHFR, having an IC50 in the picomolar range. This chemical demonstrates superior intracellular transport via the reduced folate carrier, and increased accumulation within cells by enhanced polyglutamylation. It exhibits antitumor activity that is superior to the activity of other antifolates. Its enhanced activity relative to methotrexate (MTX) is due to its much more rapid rate of transport and polyglutamation, the former less important when the carrier is saturated.
In vivo
Pralatrexate treatment results in treatment-related toxicity in MV522 mice models, as determined by significant weight loss in some animals prior to death; however, remaining mice regains all lost weight by Day 35.
References
  • [4] https://pubmed.ncbi.nlm.nih.gov/23881211/

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2026-05-11)

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT07225985 RECRUITING
Recurrent T-Cell Non-Hodgkin Lymphoma; Refractory T-Cell Non-Hodgkin Lymphoma
Fred Hutchinson Cancer Center
2026-04-27 PHASE1; PHASE2
NCT06072131 RECRUITING
Peripheral T Cell Lymphoma
Acrotech Biopharma Inc.
2023-10-04 PHASE3
NCT07691450 NOT_YET_RECRUITING
Recurrent Anaplastic Large Cell Lymphoma; Recurrent Enteropathy-Associated T-Cell Lymphoma; Recurrent Follicular Helper T-Cell Lymphoma; Recurrent Follicular Helper T-Cell Lymphoma, Angioimmunoblastic-Type; Recurrent Follicular Helper T-Cell Lymphoma, Follicular-Type; Recurrent Follicular Helper T-Cell Lymphoma, Not Otherwise Specified; Recurrent Hepatosplenic T-Cell Lymphoma; Recurrent Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Recurrent Monomorphic Epitheliotropic Intestinal T-cell Lymphoma; Recurrent Peripheral T-Cell Lymphoma, Not Otherwise Specified; Recurrent Primary Cutaneous CD8-Positive Aggressive Epidermotropic Cytotoxic T-Cell Lymphoma; Recurrent Primary Cutaneous Gamma-Delta T-Cell Lymphoma; Recurrent Subcutaneous Panniculitis-Like T-Cell Lymphoma; Refractory Anaplastic Large Cell Lymphoma; Refractory Enteropathy-Associated T-Cell Lymphoma; Refractory Follicular Helper T-Cell Lymphoma; Refractory Follicular Helper T-Cell Lymphoma, Angioimmunoblastic-Type; Refractory Follicular Helper T-Cell Lymphoma, Follicular-Type; Refractory Follicular Helper T-Cell Lymphoma, Not Otherwise Specified; Refractory Hepatosplenic T-Cell Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Refractory Monomorphic Epitheliotropic Intestinal T-cell Lymphoma; Refractory Peripheral T-Cell Lymphoma, Not Otherwise Specified; Refractory Primary Cutaneous CD8-Positive Aggressive Epidermotropic Cytotoxic T-Cell Lymphoma; Refractory Primary Cutaneous Gamma-Delta T-Cell Lymphoma; Refractory Subcutaneous Panniculitis-Like T-Cell Lymphoma
City of Hope Medical Center
2027-01-03 PHASE1
NCT04747236 RECRUITING
PTCL
University of Virginia
2021-02-19 PHASE2
NCT06561048 RECRUITING
Peripheral T-Cell Lymphoma, Not Otherwise Specified; Angioimmunoblastic T-cell Lymphoma; Follicular T-Cell Lymphoma; Nodal Peripheral T-Cell Lymphoma With TFH Phenotype; Systemic Anaplastic Large Cell Lymphoma; Lymphoma, T-Cell, Peripheral; Lymphoma, T-Cell
Corvus Pharmaceuticals, Inc.
2024-10-02 PHASE3
NCT06671717 NOT_YET_RECRUITING
Relapsed Peripheral T-Cell Lymphoma; Refractory Peripheral T-Cell Lymphoma
Peking University People's Hospital
2024-12

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Frequently Asked Questions

Question 1:
We are just wondering if it is a racemic mixture or a monomer? Will you please let us know?

Answer:
It is the S enantiomer.

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