The Action of Pteroylglutamic Conjugates on Man

Farber, Sidney; Cutler, Elliott C.; Hawkins, James W.; Harrison, John; Peirce, E. Converse; Lenz, Gilbert G.

doi:10.1126/science.106.2764.619

Cited by 114 publications

(54 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Folate derivatives are essential one-carbon donors required for the synthesis of nucleic acid precursors and several amino acids, and are therefore critical to the de novo synthesis of DNA and proliferation of mammalian cells. After folates were discovered to be essential for many cellular processes, the development of fraudulent mimics of folic acid began to emerge, which initially included drugs like, aminopterin and methotrexate, which were synthesized in the early 1940s (2). In 1948, aminopterin was the first drug shown to induce temporary remissions in childhood leukemia (2,3).…”

Section: Introductionmentioning

confidence: 99%

“…After folates were discovered to be essential for many cellular processes, the development of fraudulent mimics of folic acid began to emerge, which initially included drugs like, aminopterin and methotrexate, which were synthesized in the early 1940s (2). In 1948, aminopterin was the first drug shown to induce temporary remissions in childhood leukemia (2,3). Soon thereafter, methotrexate became the more commonly used antifolate in the treatment of many cancers, and is to this day still considered an important component of many chemotherapy regimens for solid tumors and hematologic malignancies, including: acute lymphoblastic leukemia, lymphoma, breast cancer, osteosarcoma, primary central nervous system, and head and neck cancer.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Pralatrexate Pharmacology and Clinical Development

Marchi

Mangone

Zullo

et al. 2013

Clinical Cancer Research

View full text Add to dashboard Cite

Folates are well known to be essential for many cellular processes, including cellular proliferation. As a consequence, antifolates, the fraudulent mimics of folic acid, have been shown to be potent therapeutic agents in many cancers. Over the past several decades, efforts to improve on this class of drugs have met with little success. Recently, one analog specifically designed to have high affinity for the reduced folate carrier, which efficiently internalizes natural folates and antifolates, has been shown to be very active in T-cell lymphoma. Pralatrexate, approved by the U.S. Food and Drug Administration in 2009, is highly active across many lymphoid malignancies, including chemotherapy-resistant T-cell lymphoma. Emerging combination studies have now shown that pralatrexate is highly synergistic with gemcitabine, histone deacetylase inhibitors like romidepsin and bortezomib. These insights are leading to a number of novel phase I and II combination studies which could challenge existing regimens like CHOP, and improve the outcome of patients with T-cell lymphoma Clin Cancer Res; 19(24); 6657-61. Ó2013 AACR.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pralatrexate Pharmacology and Clinical Development

Marchi

Mangone

Zullo

et al. 2013

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…To their surprise, the administration of folic acid accelerated the progression of leukemia (6). Making good of this discovery, which suggested that the proliferation of leukemia cells might be limited by the supply of folic acid, Sidney Farber went on to show that one of folic acid antagonists, aminopterin, produced complete remissions in children with acute leukemia (8).…”

mentioning

confidence: 99%

Folic Acid Supplementation and Cancer Risk: Point

Kim

2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

118

106

View full text Add to dashboard Cite

“…Based upon the observation by Lewisohn et al at the Mt. Sinai Hospital in New York City that ''folic acid concentrate'' caused regression of breast cancer in mice (3), clinical investigators led by Sidney Farber at the Children's Hospital in Boston obtained folic acid polyglutamate conjugates from Lederle Laboratories in an attempt to reproduce these findings in children with cancer (4). To their surprise, the administration of folic acid exacerbated the disease in children with leukemia.…”

mentioning

confidence: 99%

Pemetrexed: biochemical and cellular pharmacology, mechanisms, and clinical applications

Chattopadhyay

Moran

Goldman

2007

Molecular Cancer Therapeutics

245

228

View full text Add to dashboard Cite

Pemetrexed is a new-generation antifolate, approved for the treatment of mesothelioma and non -small cell lung cancer, currently being evaluated for the treatment of a variety of other solid tumors. This review traces the history of antifolates that led to the development of pemetrexed and describes the unique properties of this agent that distinguish it from other antifolates. These include (a) its very rapid conversion to active polyglutamate derivatives in cells that build to high levels and are retained for long intervals to achieve prolonged and potent inhibition of its major target enzyme thymidylate synthase, (b) its high affinity for three folate transporters, and (c) its marked sensitivity to the level of physiologic folates in cells. The latter results in the unique and paradoxical finding that when transport mediated by the major folate transporter (the reduced folate carrier) is impaired, pemetrexed activity is preserved. This is due to concurrent contraction of competing cellular physiologic folates and utilization of a novel second transport carrier for which pemetrexed has high affinity, recently identified as the proton-coupled folate transporter (PCFT). Laboratory studies are reviewed that raise the possibility of new approaches to the use of folic acid supplementation in clinical regimens with pemetrexed. [Mol Cancer Ther 2007;6(2):404 -17]

show abstract

The Action of Pteroylglutamic Conjugates on Man

Cited by 114 publications

References 8 publications

Pralatrexate Pharmacology and Clinical Development

Pralatrexate Pharmacology and Clinical Development

Folic Acid Supplementation and Cancer Risk: Point

Pemetrexed: biochemical and cellular pharmacology, mechanisms, and clinical applications

Contact Info

Product

Resources

About