MDL | MFCD00920897 |
---|---|
Molecular Weight | 477.47 |
Molecular Formula | C23H23N7O5 |
SMILES | O=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 |
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] .
Ki: 13.4 pM (Dihydrofolate reductasean (DHFR)) [4]
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. |
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. |
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 |
NCT03150602 | Taiwan Mundipharma Pharmaceuticals Ltd. |
Peripheral T Cell Lymphoma|Progression, Disease
|
August 30, 2016 | Phase 4 |
NCT03161223 | University of Virginia |
Lymphoma, T-Cell
|
May 30, 2018 | Phase 1|Phase 2 |
NCT00554827 | Acrotech Biopharma Inc. |
Cutaneous T-cell Lymphoma
|
August 2007 | Phase 1 |
NCT01420679 | Spectrum Pharmaceuticals, Inc |
Peripheral T-cell Lymphoma
|
August 2011 | Phase 3 |
NCT00481871 | Acrotech Biopharma Inc. |
Relapsed or Refractory Lymphoproliferative Malignancies|Hodgkin´s Lymphoma|Peripheral T-cell Lymphoma|B-cell Lymphoma|Waldenstrom´s Macroglobulinemia
|
May 2007 | Phase 1|Phase 2 |
NCT01118624 | Acrotech Biopharma Inc. |
Breast Cancer|Breast Tumors|Neoplasms, Breast|Cancer of the Breast|Human Mammary Carcinoma
|
March 2010 | Phase 2 |
NCT00052442 | Spectrum Pharmaceuticals, Inc|National Cancer Institute (NCI)|Memorial Sloan Kettering Cancer Center |
Lymphoma
|
August 2002 | Phase 1|Phase 2 |
NCT00722553 | Acrotech Biopharma Inc. |
Carcinoma, Transitional Cell|Bladder Cancer|Bladder Neoplasm
|
July 2008 | Phase 2 |
NCT01947140 | Jennifer Amengual|Columbia University |
Lymphoid Malignancies|Multiple Myeloma|Lymphoma|Hodgkin Lymphoma|Non-hodgkin Lymphoma
|
September 9, 2013 | Phase 1|Phase 2 |
NCT00024245 | Memorial Sloan Kettering Cancer Center|National Cancer Institute (NCI) |
Unspecified Adult Solid Tumor, Protocol Specific
|
May 2001 | Phase 1 |
NCT01626664 | Kyowa Kirin, Inc. |
Adult T-cell Leukemia-Lymphoma
|
June 2012 | Phase 2 |
NCT03355768 | Jennifer Amengual|Columbia University |
Lymphoma, T-Cell, Peripheral
|
September 1, 2018 | Phase 3 |
NCT01336933 | University of Nebraska|National Cancer Institute (NCI)|Spectrum Pharmaceuticals, Inc |
Anaplastic Large Cell Lymphoma|Angioimmunoblastic T-cell Lymphoma|Hepatosplenic T-cell Lymphoma|Peripheral T-cell Lymphoma
|
July 2011 | Phase 2 |
NCT01134341 | Acrotech Biopharma Inc. |
Cutaneous T-cell Lymphoma|Mycosis Fungoides|Sezary Syndrome|Primary Cutaneous Anaplastic Large Cell Lymphoma
|
March 2010 | Phase 1 |
NCT01482962 | Millennium Pharmaceuticals, Inc.|Takeda |
Relapsed Peripheral T-Cell Lymphoma|Refractory Peripheral T-Cell Lymphoma
|
June 11, 2012 | Phase 3 |
NCT00364923 | Acrotech Biopharma Inc. |
Peripheral T-cell Lymphoma
|
August 2006 | Phase 2 |
NCT03598998 | City of Hope Medical Center|National Cancer Institute (NCI) |
Anaplastic Large Cell Lymphoma|Nodal Peripheral T-Cell Lymphoma With TFH Phenotype|Recurrent Anaplastic Large Cell Lymphoma|Recurrent Angioimmunoblastic T-Cell Lymphoma|Recurrent Enteropathy-Associated T-Cell Lymphoma|Recurrent Follicular Lymphoma|Recurrent Hepatosplenic T-Cell Lymphoma|Recurrent Mature T- Cell and NK-Cell Non-Hodgkin Lymphoma|Recurrent Monomorphic Epitheliotropic Intestinal T-cell Lymphoma|Recurrent Mycosis Fungoides|Recurrent Peripheral T-Cell Lymphoma, Not Otherwise Specified|Refractory Anaplastic Large Cell Lymphoma|Refractory Angioimmunoblastic T-Cell Lymphoma|Refractory Enteropathy-Associated T-Cell Lymphoma|Refractory Follicular Lymphoma|Refractory Hepatosplenic T-Cell Lymphoma|Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma|Refractory Mycosis Fungoides|Refractory Peripheral T-Cell Lymphoma, Not Otherwise Specified|Subcutaneous Panniculitis-Like T-Cell Lymphoma
|
February 4, 2019 | Phase 1|Phase 2 |
NCT04747236 | University of Virginia|Celgene |
PTCL
|
February 19, 2021 | Phase 2 |
NCT00004238 | Memorial Sloan Kettering Cancer Center|National Cancer Institute (NCI) |
Lung Cancer
|
July 1999 | Phase 2 |
NCT00606502 | Spectrum Pharmaceuticals, Inc |
Non-small Cell Lung Cancer
|
January 2008 | Phase 2 |
NCT01188876 | Massachusetts General Hospital|Dana-Farber Cancer Institute|Brigham and Women´s Hospital|National Comprehensive Cancer Network |
Ovarian Cancer|Fallopian Tube Cancer|Peritoneal Cancer
|
August 2010 | Phase 1|Phase 2 |
NCT01206465 | University of Nebraska|National Cancer Institute (NCI) |
Unspecified Adult Solid Tumor, Protocol Specific
|
September 2010 | Phase 1 |
NCT02013362 | Mundipharma K.K. |
Peripheral T-cell Lymphoma
|
March 2014 | Phase 1|Phase 2 |
NCT03356678 | Samsung Medical Center |
Relapsed or Refractory Peripheral T-cell Lymphoma
|
September 23, 2016 | |
NCT01178944 | Roswell Park Cancer Institute|National Cancer Institute (NCI)|National Comprehensive Cancer Network |
Adenocarcinoma of the Gastroesophageal Junction|Esophageal Undifferentiated Carcinoma|Gastric Adenocarcinoma|Gastric Squamous Cell Carcinoma|Recurrent Esophageal Adenocarcinoma|Recurrent Esophageal Squamous Cell Carcinoma|Recurrent Gastric Carcinoma|Stage IIIB Esophageal Adenocarcinoma|Stage IIIB Esophageal Squamous Cell Carcinoma|Stage IIIB Gastric Cancer|Stage IIIC Esophageal Adenocarcinoma|Stage IIIC Esophageal Squamous Cell Carcinoma|Stage IIIC Gastric Cancer|Stage IV Esophageal Adenocarcinoma|Stage IV Esophageal Squamous Cell Carcinoma|Stage IV Gastric Cancer|Undifferentiated Gastric Carcinoma
|
September 2010 | Phase 2 |
NCT00998946 | Spectrum Pharmaceuticals, Inc |
Lymphoma, B-Cell
|
September 2009 | Phase 2 |
NCT01129206 | Ohio State University Comprehensive Cancer Center|National Comprehensive Cancer Network|Spectrum Pharmaceuticals, Inc |
Adenocarcinoma of the Esophagus|Adenocarcinomas of the Gastroesophageal Junction|Recurrent Esophageal Cancer|Squamous Cell Carcinoma of the Esophagus|Stage IV Esophageal Cancer
|
July 2010 | Phase 2 |
NCT03349333 | Mundipharma (China) Pharmaceutical Co. Ltd |
Refractory Peripheral T-Cell Lymphoma|Relapsed T-Cell Lymphoma
|
September 10, 2015 | Phase 3 |
NCT01532011 | M.D. Anderson Cancer Center |
Advanced Cancers|Solid Tumors
|
March 2012 | Phase 1 |
NCT01114282 | Stanford University|National Comprehensive Cancer Network |
Multiple Myeloma
|
August 2010 | Phase 1 |
Solid
Room temperature in continental US; may vary elsewhere.
Powder | -20°C | 3 years |
---|---|---|
4°C | 2 years | |
In solvent | -80°C | 6 months |
-20°C | 1 month |
DMSO : ≥ 50 mg/mL ( 104.72 mM )
* "≥" means soluble, but saturation unknown.
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 |
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