Antifolate C2 (AGF 154) has antitumor activity with an IC of 0.14 nM measured in a growth inhibition assay of human tumor cells.Antifolate C2 can be used for the study of cancer and autoimmune diseases.

Antifolate C1 is an inhibitor of de novo purine biosynthesis. Antifolate C1 has selectivity for cellular uptake by high affinity folate receptors and the proton-coupled folate transporter (PCFT) over the reduced folate carrier (RFC).

Methotrexate (WR19039) is a folate analog, an inhibitor of the dihydrofolate reductase DHFR. Methotrexate has antimetabolic, antitumor, and immunosuppressive activities, and is commonly used in rheumatoid arthritis and various tumors.

Trimethoprim (NSC-106568) is a Dihydrofolate Reductase Inhibitor Antibacterial. The mechanism of action of trimethoprim is as a Dihydrofolate Reductase Inhibitor, and Cytochrome P450 2C8 Inhibitor, and Organic Cation Transporter 2 Inhibitor.

Folinic acid calcium (Leucovorin Calcium) is the active metabolite of folic acid. Leucovorin is used principally as an antidote to folic acid antagonists.

Pemetrexed (LY-231514 Disodium Hydrate), a guanine-derived antineoplastic agent, binds to and inhibits the enzyme thymidylate synthase (TS).

P 218 is a novel DHFR inhibitor with antimalarial activity and antifolate effects and can be used to study Buruli ulcer.

Proguanil hydrochloride (Chloroquanil) is a biguanide compound which metabolizes in the body to form cycloguanil, an anti-malaria agent.Upon hydrolysis, Proguanil hydrochloride is converted to its active cyclic triazine metabolite, cycloguanil, by a cytochrome P450 dependent reaction. Cycloguanil selectively inhibits the bifunctional dihydrofolate reductase-thymidylate synthase of plasmodium parasite, thereby disrupting deoxythymidylate synthesis and ultimately blocking DNA and protein synthesis in the parasite.

Talotrexin ammonium is a non-polyglutamic acid antifolate. Talotrexin ammonium inhibits tumor growth by targeting dihydrofolate reductase (DHFR), thereby improving anti-tumor activity in a wide range of cancer models, helping to inhibit tumor growth.

Phototrexate is a photoswitchable potent inhibitor of human dihydrofolate reductase (DHFR). Phototrexate is a photochromic analog of Methotrexate. Antifolate activity is switched on (cis-Phototrexate) by UVA (375 nm) light; it can be switched off (trans-Phototrexate) by blue or white light and by thermal relaxation in the dark.cis-Phototrexate (IC50 = 6 nM) significantly reduces the viability of HeLa cells compared withtrans-Phototrexate (IC50 = 34 μM).

LSN 3213128, anti-tumor activity. is a selective, nonclassical, orally bioavailable antifolate with potent and specific inhibitory activity for aminoimidazole-4-carboxamide ribonucleotide formyltransferase (AICARFT), with IC50 of 16 nM for AICARFT enzyme inhibiton and 19 nM in cells.

Methotrexate metabolite (DAMPA) (DAMPA) is the active metabolite of Methotrexate. Methotrexate is a folic acid antagonist. Methotrexate is used as a chemotherapeutic agent and immunosuppressant.

Lometrexol (LY 264618), an antipurine Antifolate, can inhibit the activity of glycinamide ribonucleotide formyltransferase (GARFT) but do not induce detectable levels of DNA strand breaks. Lometrexol can further inhibit de novo purine synthesis, causing abnormal cell proliferation and Apoptosis, even cell cycle arrest. Lometrexol has anticancer activity. Lometrexol also is a potent human Serine hydroxymethyltransferase1/2 (hSHMT1/2) inhibitor.

Pemetrexed disodium hemipenta hydrate (LY-231514 Disodium Hydrate) is a new-type antifolate and antimetabolite for TS, DHFR, and GARFT. The Ki of Pemetrexed Disodium Hydrate for TS, DHFR and GARFT is 1.3 nM, 7.2 nM and 65 nM, respectively.

Calcium N5-methyltetrahydrofolate (NSC-173328) is the calcium salt of levomefolic acid, which has been proposed for treatment of cardiovascular disease and advanced cancers such as breast and colorectal cancers

DHFR-IN-3 (7-bromoquinazoline-2,4-diamine) is a dihydrofolate reductase (DHFR) inhibitor.

Fanotaprim is a dihydrofolate reductase (DHFR) inhibitor. Fanotaprim inhibits the growth of T. gondii strains with a TgDHFR IC50 of 1.57 ± 0.11 nM and a hDHFR IC50 of 308 ± 71 nM and a hDHFR to TgDHFR selectivity ratio of 196.

1,1,3-Tribromoacetone is an impurity of Methotrexate [1]. Methotrexate is an antimetabolite and antifolate drug that blocks the enzyme dihydrofolate reductase, stopping the transformation of folic acid into tetrahydrofolate and inhibiting DNA synthesis [1].

Tnp 351 is a novel antifolate drug being assessed for chemotherapy of lung cancer.

PD 130883 is a potent lipophilic quinazoline antifolate.

Diaveridine (AI3-23935) (DVD) is a popular antibacterial synergist that is widely used in combination with sulfonamide. It has been reported to be genotoxic to mammalian cells, but more studies are required to clarify this.

Levoleucovorin Calcium (CL307782), a calcium salt of the folinic acid, is used in cancer chemotherapy as an adjuvant.

Pralatrexate (10-Propargyl-10-deazaaminopterin) is a folate analogue inhibitor of dihydrofolate reductase (DHFR) exhibiting high affinity for reduced folate carrier-1 (RFC-1) with antineoplastic and immunosuppressive activities.

Talotrexin (PT523), an analog of Aminopterin, is a nonpolyglutamatable classic antifolate that acts as a specific inhibitor of the reduced folate carrier (RFC). It selectively inhibits RFC transport, demonstrating antitumor activity by targeting dihydrofolate reductase (DHFR) to inhibit tumor growth [1] [2].

CI-898 HCl is a lipophilic antifolate inhibitor of dihydrofolate reductase (DHFR). It has enhanced binding to DHFR in the presence of the cofactor NADPH. Cl-898 HCl inhibits cell growth and halts the cell cycle at the G1/S phase in L1210 mouse lymphocytic leukemia cells and is active against methotrexate-resistant cancer cell lines. It also enhances the activity of doxorubicin, cyclophosphamide, and 6-thioguanine (6-TG) in mice with advanced stage P338 leukemia.

LY 254155, an antifolate,binds to mFBP and inhibits hGARFT with Kis of 1.7±0.1 and 2.1±0.2 nM, respectively.

Pyrimethamine (Pirimecidan) is a competitive inhibitor of dihydrofolate reductase (DHFR), used as an antimalarial drug.

Methotrexate disodium is an tetrahydrofolate dehydrogenase inhibitor

Folinic Acid Calcium Salt Pentahydrate (Leucovorin Calcium Pentahydrate), a reduced folic acid, is used in combination with other chemotherapeutics.

Metoprine is a potent inhibitor of histamine N-methyltransferase (HMT), with potential antineoplastic activity.

DDCPPB-Glu is a 6-5 fused ring heterocycle antifolate that shows antitumor activity.

Edatrexate (CGP 30694), also known as 10-Ethyl-10-deazaaminopterin, is an analog of Methotrexate that demonstrates antitumor activity against Methotrexate-resistant tumors. This antifolate antimetabolite is utilized in research related to non-small-cell lung cancer, breast cancer, non-Hodgkin's lymphoma, and head and neck cancer [1] [2].

11-Oxahomoaminopterin exhibits antifolate activity against two folate-requiring microorganisms and inhibited Lactobacillus casei DHFR.

Levomefolate calcium is an artificial form of folate. It is a coenzymated form of folic acid and a more bioavailable alternative in dietary supplements.

Antileishmanial agent-22 (compound 15b) serves as an antiparasitic and antibacterial, exhibiting activities against Leishmania (IC50 = 0.408 μM), malaria, and tuberculosis. It operates on an antifolate mechanism, suppressing both folic and folinic acids with 88% and 94% efficacy at 100 μM, respectively. This compound also demonstrates a 96.67% inhibitory effect on P. berghei in vivo/in vitro at 48.4 μM/kg/day and 0.038 μM (IC50), and it inhibits M. tuberculosis with an MIC of 28.44 μM [1].

DQn-1, a potent antifolate, demonstrates efficacy against Mycobacterium tuberculosis (Mtb) with an MIC 90 of 0.03 µM. It inhibits the DHFR enzyme, exhibiting IC 50 values of 8.7 nM for Mtb DHFR and 7.6 nM for the human counterpart [1].

WR99210 is a potent, orally available and less toxic dihydrofolate reductase (DHFR) inhibitor (IC50<0.075 nM). WR99210 has good antiparasitic activity against P. vivax and P. falciparum strains (including P. falciparum strains resistant to Pyrimethamine ) and T. gondii.

Aminopterin (4-Aminofolic acid) is a synthetic folic acid derivative whose metabolite is a competitive inhibitor of dihydrofolate reductase

Arfolitixorin is an antifolate modulator.

Lometrexol hydrate (DDATHF hydrate) is an antipurine antifolate compound that inhibits glycinamide ribonucleotide formyltransferase (GARFT) activity without inducing detectable DNA strand breaks. It further disrupts de novo purine synthesis, leading to abnormal cell proliferation, apoptosis, and cell cycle arrest, exhibiting anticancer activity [1] [2]. Additionally, it acts as a potent inhibitor of human Serine hydroxymethyltransferase1/2 (h SHMT1/2) [3].

N-Methyl pemetrexed, an impurity found in Pemetrexed, serves as an antifolate cytotoxic agent utilized in cancer research [1].

Lometrexol (DDATHF) disodium is a potent inhibitor of human serine hydroxymethyltransferase 1/2 (hSHMT1/2) and antifolate, which reduces the activity of glycinamide ribonucleotide formyltransferase (GARFT) without causing detectable levels of DNA strand breaks. Lometrexol disodium exhibits anticancer effects by inhibiting the de novo synthesis of purines, causing abnormal cell proliferation, apoptosis and cell cycle arrest.

OYYF-175 is an antimicrobial antifolate. OYYF-175 exhibits potent broad-spectrum antibacterial activities, especially against multi-drug resistant Gram-Negative-strains. OYYF-175 is an inhibitor of dihydrofolate reductase (DHFR) with an IC 50 of 2.36 nM for Escherichia coli DHFR.

ICI 198583 is an inhibitor of antifolate thymidylate synthase.

Pemetrexed disodium (LY-231514) is a parenterally administered folate antagonist and antineoplastic agent, used in the treatment of non-small cell lung cancer and malignant mesothelioma. Pemetrexed disodium therapy has been associated with moderate rates of serum enzyme elevations during therapy, but has not been convincingly linked to instances of acute, clinically apparent liver injury.