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.
The company is currently developing a library of metabolically inert antifolate
compounds engineered to have potent anti-inflammatory and anti-tumor activity to treat a range of immunological disorders.
In conclusion, our findings collectively indicate that endogenous pretreatment plasma folate may play a decisive role in modulating the whole-body antifolate
effect of MTX, providing support for an original "folate overrescue" concept.
Preclinical and clinical data to date suggests superior safety and tolerability, as well as increased potency versus methotrexate, or MTX, currently the leading antifolate
treatment and standard of care for a broad range of abnormal cell proliferation diseases.
Mechanisms of resistance of malaria parasites to antifolates
The proceeds from the private placement will be used primarily to fund clinical and non-clinical research and development of its patented CH-1504 drug, preclinical development of additional antifolates
in the pipeline, licensing additional clinical drug candidates, working capital and general corporate purposes.
Raising folate intake in women with breast cancer doesn't appear to curb the benefits of antifolate
chemotherapeutic agents like methotrexate, Thomas A.
Methotrexate (MTX) is an antifolate
drug that inhibits dihydrofolate reductase, thereby depleting the cells of reduced folates, including 5-methyltetrahydrofolate (5).
Shih contributed to the successful antifolate
drug discovery program that has led to the development of ALIMTA([R]), a blockbuster anticancer agent approved by various regulatory agencies around the globe for the treatment of mesothelioma and non-small cell lung cancer.
MedPredict's panel also reviews recent advances in other mechanistic approaches to treatment, including angiogenesis/VEGF, vascular disrupting agents, anthracyclines, TRAIL / DR4 / DR5, Bcl-2/Bcl-xL, survivin, cyclin dependent kinase, cMET, EGFR (T790M), antifolate
, HDAC / epigenetics, Hedgehog, HSP90, IGF-1, MAGE-A3, MEK, microtubule, apoptosis, kinesin/EG5, aurora kinase, Polo-like kinase 1, mTOR, PI3/AKT, KRAS, and topoisomerase.
Even increased numbers of gametocytes produced after SP treatment are transmitted poorly through the mosquito because of the antifolate
action of pyrimethamine (27,28).
In addition, Allos is developing PDX (pralatrexate), a novel small molecule cytoxic injectable antifolate
(DHFR inhibitor) that is currently being investigated in patients with non-small cell lung cancer and non-Hodgkin's lymphoma.
Pralatrexate is a selective antifolate
designed to accumulate preferentially in cancer cells.
The findings from this Phase I trial continue to validate the strength of Chelsea's antifolate
portfolio," commented Dr.
Researchers are pursuing a broad array of mechanistic approaches to treatment, including angiogenics/VEGF, EGFR resistance (T790M, MET), HER2 (ErbB2), antifolate
, anti-microtubule, apoptosis, Bcl-2/Bcl-xL, TRAIL, vascular disrupting agents, Ras, Raf, MEK, mTOR, PI3, AKT, IGF-1, HSP90, HDAC, JAK/STAT, MAGE-A3, CDK, Aurora Kinase, and anticoagulation.