DHFR

Key enzyme in folate metabolism.

QDPR-IN-1 (Compound 9b) is an effective inhibitor of QDPR, exhibiting an IC50 value of 0.72 μM.

DHFR-IN-5: potent, oral DHFR inhibitor, Ki 0.54 nM against mutant P. falciparum, anti-malarial.

10-Deazaaminopterin is a poly-gamma-glutamyl metabolite of the experimental anticancer drug, a folic acid antagonist, antineoplastic agent enzyme inhibitor.

Clociguanil has antimalarial activity.

Piritrexim (BW 301U) is an orally available fat-soluble dihydrofolate reductase inhibitor with pulmonary toxicity used in the study of uroepithelial carcinoma

Managlinat dialanetil, an orally available and potent inhibitor of fructose 1,6-bisphosphatase (FBPase) used in research 2 type diabetes.

Aditoprime (Aditoprim) is a selective bacterial DHFR inhibitor with strong nanomolar potency and broad-spectrum antibacterial activity.

TH9028 is an inhibitor targeting MTHFD1, MTHFD2, and MTHFD2L, with IC50 values against the human-derived targets of 0.5 nM (MTHFD1), 11 nM (MTHFD2), and 27 nM (MTHFD2L), respectively. This compound binds to the substrate-binding region of the target enzymes, forming hydrogen bonds and other interactions with key amino acid residues, while also inducing conformational changes in the loop 1 region of the enzyme. Functionally, TH9028 slows down the progression of replication forks, induces replication stress, causes cell cycle arrest at the S phase, promotes apoptosis, inhibits thymidine synthesis, and leads to the misincorporation of uracil into DNA. In acute myeloid leukemia and T-ALL cells, TH9028 exhibits antiproliferative activity, while its effects on non-transformed cells are relatively weak. Therefore, TH9028 can be used in research related to acute myeloid leukemia.

Methotrexate-gamma-aspartate has growth inhibitory effects. It is used in antibody-targeted liposomes.

Phototrexate, a photochromic Methotrexate analog, is a UVA-activated, reversible DHFR inhibitor with antifolate properties (IC50: 6 nM cis vs. 34 μM trans).

DHFR-IN-4 is a potent dihydrofolate reductase (DHFR) inhibitor with anti-tumour activity, inhibits EGFR and HER2 and can be used to study pancreatic cancer.