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LY231514, a pyrrolopyrimidine-based antifolate that inhibits multiple folate-requiring enzymes.
He had also developed another version of antifolate -- aminopterin.
Studies provided the collaborators with the information they needed to exploit this feature of cancer cells and to develop an antifolate that would be more effectively transported into the cells via RFC-1.
Molecular epidemiology of Plasmodium falciparum antifolate resistance in Vietnam: genotyping for resistance variants of dihydropteroate synthase and dihydrofolate reductase.
We first addressed the question of whether tHcy could serve as a marker of folate status in patients with psoriasis, rheumatoid arthritis, or cancer who were treated with a wide range of doses of the antifolate agent methotrexate (3).
Methotrexate, a folate antagonist, was originally developed as an anticancer agent, (34) In addition to its antifolate action, methotrexate has been proposed to inhibit T-cell proliferation via effects on purine and pyrimidine metabolism; to inhibit transmethylation reactions required for T-cell cytotoxicity; to promote the release of adenosine, an endogenous anti-inflammatory mediator; and to interfere with glutathione metabolism, and hence, alter the recruitment of monocytes to the inflamed joint.
has begun dosing volunteers in its bioequivalence study of CH-1504, an orally available metabolically inert antifolate which has demonstrated potential anti-inflammatory and anti-tumor properties.
Allos has two product candidates in late-stage clinical development: EFAPROXYN (efaproxiral), a radiation sensitizer currently under evaluation in a pivotal Phase 3 trial in women with brain metastases originating from breast cancer, and PDX (pralatrexate), a novel, next-generation antifolate currently under evaluation in a pivotal Phase 2 trial in patients with relapsed or refractory peripheral T-cell lymphoma.
Evidence for a localized conversion of endogenous tetrahydrofolate cofactors to dihydrofolate as an important element in antifolate action in murine leukemia cells.
In addition, there have been reports of neural tube defects thought to be secondary to the antifolate activity of TMP (Eur.
A major factor in the resistance of cells to antifolate cancer treatment involves nucleoside salvage from the extracellular media.