MTHFS Inhibitors
MTHFS inhibitors are a class of chemical compounds that target and inhibit the activity of methenyltetrahydrofolate synthetase (MTHFS), an enzyme that plays a crucial role in the folate cycle. MTHFS catalyzes the ATP-dependent conversion of 5-formyltetrahydrofolate (5-formyl-THF), also known as folinic acid, into 5,10-methenyltetrahydrofolate (5,10-methenyl-THF). This reaction is important because 5,10-methenyl-THF serves as a cofactor in various biochemical pathways, including purine biosynthesis and the formation of formylated methionine-tRNA required for protein translation. Inhibiting MTHFS affects the regulation of folate derivatives, particularly disrupting the balance between 5-formyl-THF and other folate species. This disruption may have downstream effects on cellular processes that depend on folate intermediates, such as nucleotide synthesis and methylation reactions.
The molecular structure of MTHFS inhibitors typically consists of scaffolds that can effectively interact with the active site of the enzyme, binding in a way that prevents the conversion of 5-formyl-THF to 5,10-methenyl-THF. These inhibitors are designed to achieve high specificity for MTHFS to minimize interference with other enzymes in the folate pathway, such as dihydrofolate reductase (DHFR) or thymidylate synthase. Structural studies have revealed that these inhibitors often mimic the natural substrates of MTHFS, engaging in hydrogen bonding and hydrophobic interactions with key residues within the enzyme's binding pocket. The study of MTHFS inhibitors provides valuable insights into the regulation of folate metabolism, particularly in understanding the mechanistic aspects of enzyme inhibition and the resulting biochemical shifts in folate-dependent pathways.
SEE ALSO...
| Product Name | CAS # | Catalog # | QUANTITY | Price | Citations | RATING |
|---|---|---|---|---|---|---|
Methotrexate | 59-05-2 | sc-3507 sc-3507A | 100 mg 500 mg | $94.00 $213.00 | 33 | |
Methotrexate competitively inhibits dihydrofolate reductase, leading to a reduction in tetrahydrofolate and other folate derivatives, potentially downregulating MTHFS expression as a compensatory cellular response to preserve folate metabolism homeostasis. | ||||||
Aminopterin | 54-62-6 | sc-202461 | 50 mg | $102.00 | 1 | |
Aminopterin acts similarly to methotrexate with potent inhibition of dihydrofolate reductase, which could result in a decrease in MTHFS expression due to the depletion of substrates necessary for its enzymatic activity and the ensuing disruption of folate metabolism. | ||||||
Raltitrexed | 112887-68-0 | sc-219933 | 10 mg | $146.00 | ||
Raltitrexed is a thymidylate synthase inhibitor that could lead to an accumulation of dihydrofolate, and consequently, a feedback decrease in the expression of MTHFS as part of the cellular effort to balance the disrupted folate pools. | ||||||
Pyrimethamine | 58-14-0 | sc-208190 sc-208190A sc-208190B | 1 g 5 g 25 g | $80.00 $238.00 $825.00 | 5 | |
Pyrimethamine's inhibition of dihydrofolate reductase in protozoa, and at higher concentrations in mammalian cells, could decrease the cellular concentrations of folate, leading to a subsequent downregulation of MTHFS expression as the cell attempts to manage limited folate resources. | ||||||
Trimethoprim | 738-70-5 | sc-203302 sc-203302A sc-203302B sc-203302C sc-203302D | 5 g 25 g 250 g 1 kg 5 kg | $67.00 $161.00 $255.00 $721.00 $3401.00 | 4 | |
Trimethoprim selectively inhibits bacterial dihydrofolate reductase but at elevated levels may exert a similar effect on mammalian cells, potentially decreasing MTHFS expression by inducing folate scarcity within the cell, prompting a reduction in folate-dependent enzymatic processes. | ||||||
Fluorouracil | 51-21-8 | sc-29060 sc-29060A | 1 g 5 g | $37.00 $152.00 | 11 | |
Fluorouracil, a uracil analog, disrupts thymidylate synthase, which could lead to a secondary downregulation of MTHFS expression as part of a broader cellular response to impaired DNA synthesis and repair mechanisms. | ||||||
Hydroxyurea | 127-07-1 | sc-29061 sc-29061A | 5 g 25 g | $78.00 $260.00 | 18 | |
Hydroxyurea inhibits ribonucleotide reductase, which could indirectly lead to a decrease in MTHFS expression due to the overall reduction in deoxyribonucleotide pools, affecting DNA repair and replication and causing cellular stress responses that may include modulation of folate metabolism. | ||||||
Sulfamethoxazole | 723-46-6 | sc-208405 sc-208405A sc-208405B sc-208405C | 10 g 25 g 50 g 100 g | $37.00 $55.00 $69.00 $109.00 | 5 | |
Sulfamethoxazole targets bacterial dihydropteroate synthase; however, in a non-antibiotic role and at high concentrations, it could interfere with human folate absorption or metabolism, potentially reducing MTHFS expression due to a decrease in overall folate availability. | ||||||
Triamterene | 396-01-0 | sc-213103A sc-213103 | 1 g 5 g | $22.00 $54.00 | ||
Triamterene can interfere with the renal absorption of folate, which might lead to a systemic reduction in available folate, potentially necessitating a decrease in MTHFS expression as the cell downregulates certain folate-dependent pathways in response to perceived folate insufficiency. | ||||||
Folic Acid | 59-30-3 | sc-204758 | 10 g | $73.00 | 2 | |
Supraphysiological levels of folic acid could theoretically initiate a negative feedback loop, where the cell downregulates MTHFS expression to prevent excessive accumulation of folate intermediates and maintain metabolic balance. | ||||||