hfd

Lansoprazole (A-65006) is a 2, 2, 2-trifluoroethoxypyridyl derivative of timoprazole that is used in the therapy of STOMACH ULCERS and ZOLLINGER-ELLISON SYNDROME. The drug inhibits H(+)-K(+)-EXCHANGING ATPASE which is found in GASTRIC PARIETAL CELLS. Lansoprazole is a potent brain penetrant neutral sphingomyelinase (N-SMase) inhibitor (exosome inhibitor)

Lycorine (Narcissine) inhibits protein synthesis and may inhibit ascorbic acid biosynthesis, although studies on the latter are controversial and inconclusive.

PTUPB is a potent dual inhibitor of sEH and COX-2 enzymes with IC50 values of 0.9 nM and 1.26 μM, respectively.

BVT 2733 is a new, non-steroidal, isoform-specific inhibitor of 11β-HSD1.

ACH-000143 have been identified as a novel agonist of the melatonin receptors MT1 and MT2.

Ketoprofen (RP-19583) is a propionic acid derivative and nonsteroidal anti-inflammatory drug (NSAID) with anti-inflammatory, analgesic, and antipyretic effects. It inhibits cyclo-oxygenase I and II, decreasing the formation of prostaglandin and thromboxane precursors. This reduction in prostaglandin synthesis, mediated by prostaglandin synthase, is responsible for its therapeutic effects. Additionally, Ketoprofen decreases thromboxane A2 formation via thromboxane synthase, inhibiting platelet aggregation.

SBC-115076 is a potent extracellular proprotein convertase subtilisin kexin type 9 (PCSK9) antagonist.

MTHFD2-IN-5 (Compound 16e) is a selective inhibitor of MTHFD2 with an IC50 of 66 nM. It inhibits the proliferation of MOLM-14 cells with a GI50 of 720 nM and demonstrates antitumor activity in mouse models.

MTHFD2-IN-6 (compound 41) is a potent and selective inhibitor of MTHFD2, displaying inhibitory activity against both MTHFD1 and MTHFD2 with IC50 values of 19.05 μM and 1.46 μM respectively.

MTHFD1/2-IN-1 is an orally active dual inhibitor of MTHFD1 and MTHFD2, exhibiting IC50 values of 0.26 μM and 0.031 μM for human MTHFD1 and MTHFD2, respectively. It disrupts one-carbon metabolism by inhibiting the dehydrogenase activity of MTHFD1 and both the dehydrogenase and cyclohydrolase activities of MTHFD2, thereby impairing nucleotide biosynthesis and redox homeostasis in cancer cells. This compound demonstrates good Caco-2 permeability and hepatic microsome metabolic stability. Furthermore, MTHFD1/2-IN-1 shows significant anti-leukemia activity, reducing the viability of various leukemia cells and inhibiting tumor growth in mouse models of acute myeloid leukemia (AML).

MTHFD2-IN-7 is an orally active and selective inhibitor of MTHFD2, exhibiting IC50 values of 0.038 μM for human-derived hMTHFD1 and 7.44 μM for hMTHFD2. It operates by binding to the substrate binding site of MTHFD2 while maintaining interaction with NAD+. Validated by TSA and DARTS experiments, MTHFD2-IN-7 effectively binds its target protein and demonstrates Caco-2 permeability and liver microsomal metabolic stability. In mice, it shows favorable pharmacokinetic properties. Furthermore, MTHFD2-IN-7 significantly inhibits cancer cell proliferation and reduces tumor size, making it a promising small molecule tool for acute myeloid leukemia research.

MTHFD2-IN-1 (compound 12) is a potent inhibitor of methylenetetrahydrofolate dehydrogenase (MTHFD2) [1].

MTHFD2-IN-2 (compound 13) is a potent inhibitor of methylenetetrahydrofolate dehydrogenase (MTHFD2) [1].

MTHFD2-IN-3 (compound 10), a potent inhibitor of methylenetetrahydrofolate dehydrogenase (MTHFD2), demonstrates significant efficacy in obstructing the activity of this enzyme [1].

MTHFD2-IN-4, a tricyclic coumarin derivative, serves as a potent inhibitor of MTHFD2 and has applications in cancer research [1].

MTHFD2-IN-4 sodium, a potent inhibitor of MTHFD2 and a tricyclic coumarin derivative, is applicable in cancer research [1].

IKFQFHFD is a pH-responsive self-assembling peptide. It exhibits biocompatibility at neutral pH and adopts an antimicrobial peptide-like molecular structure only at acidic pH. IKFQFHFD can be used to treat chronic wounds caused by biofilm infections, such as venous ulcers, diabetic ulcers, and pressure sores.

DS18561882 is an orally available, selective and potent inhibitor of methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) with antitumor activity, inhibits MTHFD1 activity and can be used in the study of breast cancer.

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.

TH9028 TFA is an effective MTHFD2 inhibitor (IC50=11 nM) that suppresses proliferation in HL-60 cells, AML cells, and T-ALL Jurkat cells.

LY 345899 is a folate analog that inhibits methylenetetrahydrofolate dehydrogenase and MTHFD2, with IC50 values of 96 nM and 663 nM, respectively, and a Ki of 18 nM for MTHFD1.

Emofolin sodium is the sodium salt of a synthetic antimetabolite analogue of folate with antineoplastic activity,which competes for the folate binding site of the enzyme dihydrofolate reductase, resulting in inhibition of tetrahydrofolate synthesis, deple

DS44960156 is a novel selective inhibitor of methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) that inhibits both MTHFD2 and MTHFD1 and can be used in cancer research.

10 FTHF disodium (10-Formyltetrahydrofolic acid disodium) is a form of tetrahydrofolate, a formyl donor in anabolism, involved in the synthesis of purine compounds.