Therefore, in vitro drug pressure only with artemisinin selects for enhanced survival rates to endoperoxides, quinolines, and an antifolate
New therapeutic agents, such as antifolates
, histone deacetylase inhibitors, monoclonal antibodies, fusion toxins, proteasome inhibitors, immunomodulatory agents, topoisomerase inhibitors, and tyrosine kinase inhibitors, have been used for HSTL.
hasannounced that a preliminary analysis of its dose-ranging exploratory Phase II trial of CH-4051, a non- metabolized antifolate
, in patients with rheumatoid arthritis (RA) who experience an inadequate response to methotrexate (MTX) treatment indicates that CH-4051 did not demonstrate superior efficacy to methotrexate in the dose range evaluated.
The company will also use the proceeds to back the study of its CH-4051 metabolically inert oral antifolate
engineered to have anti-inflammatory and anti-tumour activity to treat certain immunological disorders.
Pemetrexed (Alimta[R] Eli Lilly) is a new antifolate
Far from giving up, he thought if folic acid was aggravating the production of white blood cells, a chemical -- perhaps an antifolate
-- could block the growth of white blood cells to leukemia.
In addition to Droxidopa, Chelsea is also developing a portfolio of metabolically inert oral antifolate
molecules engineered to have potent anti-inflammatory and anti-tumor activity to treat a range of immunological disorders, including two clinical stage product candidates: CH-1504 and CH-4051.
In vitro activities and mechanisms of resistance to antifolate
Concerns have been raised that intake of folic acid might cause harmful effects, including progression of nerve damage in B12-deficient persons; excess intake in children; accumulation of unmetabolized folic acid; blunting of antifolate
therapy (methotrexate and phenytoin); accelerated cognitive decline in the elderly; epigenetic hypermethylation; and cancer promotion (11).
19,20) MTX acts as a folate antagonist, and most of the adverse effects of MTX are related to the antifolate
activity which may mimic symptoms of folate deficiency.
Cellular and molecular mechanisms of resistance to antifolate
drugs: new analogues and approaches to overcome the resistance.
The drug is a selective antifolate
designed to accumulate preferentially in cancer cells.
We are pleased that our long-term medicinal chemistry program in the area of antifolate
therapeutic agents has resulted in development of a clinically effective drug for treatment of certain types of human cancer," stated Joseph DeGraw, Ph.
In this trial, tumour expression of TS, DPD and gamma-glutamyl hydrolase, related to antifolate
resistance , did not condition RR in both arms.
Molecular data on Plasmodium falciparum chloroquine and antifolate
resistance : a public health tool.