[CAS NO. 146464-95-1]  Pralatrexate

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PRODUCTS SPECIFICATIONS [146464-95-1]

Catalog
HY-10446
Brand
MCE
CAS
146464-95-1

DESCRIPTION [146464-95-1]

Overview

MDLMFCD00920897
Molecular Weight477.47
Molecular FormulaC23H23N7O5
SMILESO=C(CC[C@H](NC(C1=CC=C(C=C1)C(CC#C)CC2=NC3=C(N=C(N=C3N=C2)N)N)=O)C(O)=O)O

For research use only. We do not sell to patients.


Summary

Pralatrexate is an antifolate and is a potent dihydrofolate reductasean (DHFR) inhibitor with a K i of 13.4 pM. Pralatrexate is a substrate for folylpolyglutamate synthetase with improved cellular uptake and retention. Pralatrexate has antitumor activities and has the potential for relapsed/refractory T-cell lymphoma treatment [1] [2] [3] [4] .


IC50 & Target

Ki: 13.4 pM (Dihydrofolate reductasean (DHFR)) [4]


In Vitro

Pralatrexate (100 pM-200 µM; 48-72 hours; T-lymphoma cell lines) treatment exhibits concentration- and time-dependent cytotoxicity against a broad panel of T-lymphoma cell lines. The IC 50 values at 48 and 72 hours, respectively, are as follows: H9 cells, 1.1 nM and 2.5 nM; P12 cells, 1.7 nM and 2.4 nM; CEM cells, 3.2 nM and 4.2 nM; PF-382 cells, 5.5 nM and 2.7 nM; KOPT-K1 cells, 1 nM and 1.7 nM; DND-41 cells, 97.4 nM and 1.2 nM; and HPB-ALL cells, 247.8 nM and 0.77 nM. HH cells are relatively resistant after 48 hours of exposure, with the IC 50 at 72 hours being 2.8 nM [1] .
Pralatrexate (2-5.5 nM; 48-72 hours; H9, HH, P12 and PF382 cells) treatment induces potent apoptosis, and caspase-8 and caspase-9 activation [1] .
Pralatrexate (3 nM; 16-48 hours; H9 and P12 cells) treatment clearly increases p27 levels and increases the accumulation of educed folate carrier type 1 (RFC-1) in cells [1] .

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Cytotoxicity Assay [1]

Cell Line: T-lymphoma cell lines
Concentration: 100 pM-200 µM
Incubation Time: 48 hours, 72 hours
Result: Exhibited concentration- and time-dependent cytotoxicity against a broad panel of T-lymphoma cell lines.

Apoptosis Analysis [1]

Cell Line: H9, HH, P12 and PF382 cells
Concentration: 2 nM, 3 nM, 4 nM, 5.5 nM
Incubation Time: 48 hours, 72 hours
Result: Induced potent apoptosis and caspase activation.

Western Blot Analysis [1]

Cell Line: H9 and P12 cells
Concentration: 3 nM
Incubation Time: 16 hours, 24 hours, 48 hours
Result: Clearly increased p27 levels and increased the accumulation of RFC-1 in cells.

In Vivo

The addition of Pralatrexate (15 mg/kg; intraperitoneal injection; on days 1, 4, 8, and 11; SCID-beige mice) to Bortezomib (0.5 mg/kg) enhanced efficacy compared with either drug alone [1] .

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: SCID-beige mice (5-7-week-old) injected with HH cells [1]
Dosage: 15 mg/kg
Administration: Intraperitoneal injection; on days 1, 4, 8, and 11
Result: Showed superior efficacy in T-cell malignancies.

Clinical Trial

NCT Number Sponsor Condition Start Date Phase
NCT03240211 University of Virginia|Merck Sharp & Dohme LLC|Otsuka Pharmaceutical Development & Commercialization, Inc.
PTCL|CTCL
February 2, 2022 Phase 1
NCT01183065 Memorial Sloan Kettering Cancer Center|New York University Cancer Institute|NYU Langone Health|National Comprehensive Cancer Network
Head and Neck Cancer
August 2010 Phase 2
NCT02594267 Acrotech Biopharma Inc.|Axis Clinicals Limited
Peripheral T-Cell Lymphoma (PTCL)
November 10, 2015 Phase 1

Appearance

Solid


Shipping

Room temperature in continental US; may vary elsewhere.


Storage

Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month

Solvent & Solubility

In Vitro:

DMSO : ≥ 50 mg/mL ( 104.72 mM )

* "≥" means soluble, but saturation unknown.

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 2.0944 mL 10.4719 mL 20.9437 mL
5 mM 0.4189 mL 2.0944 mL 4.1887 mL
10 mM 0.2094 mL 1.0472 mL 2.0944 mL
* Please refer to the solubility information to select the appropriate solvent.
In Vivo:
  • 1.

    Add each solvent one by one: 10% DMSO >> 40% PEG300 >> 5% Tween-80 >> 45% saline

    Solubility: ≥ 2.5 mg/mL (5.24 mM); Clear solution

  • 2.

    Add each solvent one by one: 10% DMSO >> 90% (20% SBE-β-CD in saline)

    Solubility: ≥ 2.5 mg/mL (5.24 mM); Clear solution

* All of the co-solvents are available by MCE.


Synonyms

L-Glutamic acid, N-[4-[1-[(2,4-diamino-6-pteridinyl)methyl]-3-butyn-1-yl]benzoyl]-
L-Glutamic acid, N-[4-[1-[(2,4-diamino-6-pteridinyl)methyl]-3-butynyl]benzoyl]-
N-[4-[1-[(2,4-Diamino-6-pteridinyl)methyl]-3-butyn-1-yl]benzoyl]-L-glutamic acid
10-Propargyl-10-deazaaminopterin
PDX
Pralatrexate
Folotyn
NSC 754230