Folic Acid Antagonists

Inhibitors of the enzyme, dihydrofolate reductase (TETRAHYDROFOLATE DEHYDROGENASE), which converts dihydrofolate (FH2) to tetrahydrofolate (FH4). They are frequently used in cancer chemotherapy. (From AMA, Drug Evaluations Annual, 1994, p2033)

Also Known As:

Dihydrofolate Reductase Inhibitors; Folic Acid Metabolism Inhibitors; Acid Antagonist, Folic; Acid Antagonists, Folic; Antagonist, Folic Acid; Antagonists, Folic Acid; Inhibitor, Dihydrofolate Reductase; Inhibitors, Dihydrofolate Reductase; Reductase Inhibitor, Dihydrofolate; Reductase Inhibitors, Dihydrofolate; Antifolate; Antifolates; Dihydrofolate Reductase Inhibitor; Folic Acid Antagonist

Networked: 1246 relevant articles (75 outcomes, 129 trials/studies)

Relationship Network

Bio-Agent Context: Research Results

Chemical Actions and Uses
- Pharmacologic Actions: 160
  - Molecular Mechanisms of Pharmacological Action: 24
    - Enzyme Inhibitors: 1659
      - Folic Acid Antagonists: 1246

Experts

1.	Gangjee, Aleem: 28 articles (01/2022 - 05/2002)
2.	Matherly, Larry H: 28 articles (01/2022 - 01/2003)
3.	Hou, Zhanjun: 27 articles (01/2022 - 03/2007)
4.	Assaraf, Yehuda G: 19 articles (04/2016 - 01/2002)
5.	Goldman, I David: 16 articles (01/2021 - 11/2002)
6.	Zhao, Rongbao: 13 articles (01/2018 - 11/2002)
7.	Jansen, Gerrit: 10 articles (01/2021 - 01/2002)
8.	Peters, Godefridus J: 10 articles (01/2020 - 01/2002)
9.	O'Connor, Carrie: 9 articles (01/2022 - 09/2015)
10.	Polin, Lisa: 9 articles (01/2022 - 12/2011)

Related Diseases

1.	Neoplasms (Cancer) 04/01/2008 - "Recently, we found that the preinjection of an antifolate significantly improved tumor selectivity of organometallic 99mTc-radiofolates in mice. " 10/01/2021 - "As a result, drugs targeting this pathway have shown to be effective against tumor cells and pathogens, but drug resistance against the available antifolate drugs emerged quickly. " 12/01/2012 - "TS gene polymorphisms have been shown to be associated with the efficacy of antifolate treatment in enteron tumors. " 12/01/1993 - "The efficacy of antifolate drugs is related to the extent of intracellular polyglutamation in normal and cancer cells. " 09/14/2023 - "The current study takes these two sources of data-drug response and omics profiles-and uses a multi-omics investigation to uncover molecular networks that differentiate cancer cells that are sensitive or resistant to antifolates, which is a commonly used class of anticancer drugs. "
2.	Malaria 12/01/2014 - "We undertook an open-label randomised controlled trial alongside two observational cohorts in eastern Uganda, an area with high HIV prevalence, malaria transmission intensity, and antifolate resistance. " 08/14/2013 - "Effectiveness of two antifolate prophylactic strategies against malaria in HIV-positive pregnant women in Bangui, Central African Republic: study protocol for a randomized controlled trial (MACOMBA)." 03/31/2011 - "The incidence of malaria and prevalence of genotypic mutations associated with antifolate resistance were high throughout the study. " 02/06/1998 - "These studies permit detailed biochemical, kinetic, and structural analysis of drug resistance mutations and reconstruction of the probable phylogeny of antifolate resistance in malaria." 06/14/2023 - "Assessment of genetic polymorphisms associated with malaria antifolate resistance among the population of Libreville, Gabon."
3.	Non-Small-Cell Lung Carcinoma (Carcinoma, Non-Small Cell Lung) 01/01/2008 - "New data integrating multitargeted antifolates into treatment of first-line and relapsed non-small-cell lung cancer." 06/01/2003 - "10-propargyl-10-deazaaminopterin: an antifolate with activity in patients with previously treated non-small cell lung cancer." 03/01/2003 - "The purpose of this study was to evaluate ALIMTA (pemetrexed disodium, LY231514), a multi-targeted antifolate with first-line activity against non-small-cell lung cancer (NSCLC), in a second-line setting. " 04/01/2022 - "Pemetrexed-a multitargeted antifolate agent-exhibits satisfactory clinical activity in wild-type nonsquamous non-small-cell lung cancer (NSCLC) cells. " 12/01/2019 - "Pemetrexed is an antifolate metabolite used to treat non-small cell lung cancer in the adjuvant and advanced setting. "
4.	Leukemia 10/01/1998 - "In conclusion, the efficacy of novel antifolates against childhood leukemia cells can be tested with the in situ TS inhibition assay. " 01/01/1950 - "[Critical study of the remissions in the course of acute leukemia treated by exchange transfusions (comparison with spontaneous remissions and those induced by folic acid antagonists)]." 10/15/2014 - "These findings bear important implications for the rational overcoming of antifolate resistance in leukemia. " 04/30/2009 - "Here we explored the molecular basis of antifolate resistance in human MTX-resistant leukemia cell lines displaying marked loss of FPGS activity. " 04/30/2009 - "Since polyglutamylation of antifolates is crucial for their pharmacological activity in leukemia, loss of FPGS function results in decreased cellular levels of polyglutamylation-dependent antifolates and consequent drug resistance. "
5.	Falciparum Malaria (Plasmodium falciparum Malaria) 06/01/2008 - "Targeted surveillance is needed to confirm the extent of the spread of the I164L mutation and to monitor the impact of I164L on the efficacy of antifolates for intermittent preventive treatment of pregnant women and/or infants with falciparum malaria." 02/01/2003 - "Comparative efficacy of aminoquinoline-antifolate combinations for the treatment of uncomplicated falciparum malaria in Kampala, Uganda." 01/01/2013 - "CTX is safe and still efficacious for the treatment of P.falciparum malaria in non-pregnant adults and children irrespective of HIV status and antifolate resistance profiles. " 01/01/2010 - "Molecular correlates of high-level antifolate resistance in Rwandan children with Plasmodium falciparum malaria." 03/01/2007 - "In conclusion, the antifolate treatment of falciparum malaria is proportionately affecting the DHFR mutations of P. "

Related Drugs and Biologics

1.	Methotrexate (Mexate)
2.	Pemetrexed (MTA)
3.	Trimetrexate (JB11)
4.	Folic Acid Antagonists
5.	Cisplatin (Platino)
6.	Folic Acid (Vitamin M)
7.	Aminopterin
8.	Leucovorin (Folinic Acid)
9.	Reduced Folate Carrier Protein
10.	Antimalarials (Antimalarial Agents)

Related Therapies and Procedures

1.	Therapeutics
2.	Drug Therapy (Chemotherapy)
3.	Combination Drug Therapy (Combination Chemotherapy)
4.	Aftercare (After-Treatment)
5.	Radiotherapy